Sectorial R&D Performance

Biennial Report 2007-2009 9 10 Biennial Report 2007-2009 Natural Products

BASIC RESEARCH HPLC method was also developed to quantify these • active principles in the plant material, which can serve • Total Synthesis of Neohelmanticins AñD as an effective quality control method for standardization A concise total synthesis of neohelmanticins AñD has of D. scandens. (Ref: Journal of Chromatography B, been accomplished in 15 steps starting from 2007, 855, 166ñ172) commercially available gallic acid. Swern oxidation The Indian herb Oroxylum indicum is extensively used conditions, a Grignard reaction, Sharpless kinetic in traditional medicinal preparations and extracts of this resolution, and regioselective ring opening of an epoxide plant have been reported to possess diverse biological with lithium aluminum hydride (LAH) were the key activities. Earlier work has shown that hexane extract features to install the basic core, dihydroxy phenyl of the plant possesses α-glucosidase inhibitory activity . One hydroxyl group of this core was esterified and to be one of the most potent inhibitor with tiglic acid followed by the oxidation and present in it. To make productive use of this finding a esterification with corresponding acids to yield series of 8-aminomethylated derivatives were prepared neohelmanticins AñD. (Ref: Tetrahedron: Asymmetry, by Mannich reaction of oroxylin A with appropriate 2009, 20, 440ñ448) primary or secondary amines and p-formaldehyde. All • Isolation and Characterization of Novel Dimeric the compounds were tested for their α-glucosidase Alkaloids from Piper chaba inhibition activity. Some of the compounds demonstrated The genus Piper (Piperaceae) is well reputed in the significantly better α-glucosidase inhibitory activity than Indian Ayurvedic system of medicine and is a well- the parent compound (oroxylin A). (Ref: Bioorganic & known source of structurally diverse amides with the Medicinal Chemistry Letters, 2008, 18, 1659ñ1662) wide range of bioactivities such as cytotoxic, anti- The hexane extract of Hedychium spicatum showed inflammatory, insecticidal and anti-feedant. Piper chaba potent α-glucosidase inhibitory activity. Further Hunter has been traditionally used for many medicinal fractionation of this extract led to the isolation and purposes in Ayurvedic formulations. Despite extensive identification of two new labdane diterpenes with strong biological and pharmacological studies, little is known α-glucosidase inhibitory activity along with other known about the chemical constituents of this medicinally compounds possessing moderate inhibitory important herb. As part of ongoing efforts to search for potentials. This is first time that antihyperglycemic novel active metabolites from Piper species, two novel activity in H. spicatum and α-glucosidase inhibitory dimeric alkaloids chabamide F and chabamide G were activity of labdane-type diterpenes has been isolated together with known compounds such as demonstrated. (Ref: Bioorganic & Medicinal Chemistry piperine, guineensine and brachystamide B from the Letters, 2009, 19, 2562ñ2565) methanolic extract of roots of Piper chaba. (Ref: • Tetrahedron Letters, 2009, 50, 2774ñ2777) Cytotoxic Compounds The dried roots of Saussurea lappa, called costus roots, • α-Glucosidase Inhibitors are used in the traditional system of medicine for the Work on several plants has led to their identification as treatment of cancer. The efforts aimed at isolating α-glucosidase inhibitors, an indication of their potential cytotoxic compounds resulted in the identification of a as antidiabetic agents as well as other activities such new sesquiterpene lactone, isodihydrocostunolide as anticancer, anti HIV. Search for specific molecules including several other known compounds. In an attempt responsible for these activities has resulted in following to deepen the understanding of the structureñanticancer findings. activity relationships, several synthetic analogues were Derris scandens (Fabaceae) is reported to possess also prepared and studies on their cytotoxic activities numerous medicinal properties. The hexane and were carried out. The new sesquiterpene lactone extracts of Derris scandens displayed potent isolated together with costunolide and other related α-glucosidase inhibitory and moderate free radical derivatives displayed moderate activity (IC50, 27.03ñ180 scavenging activities. Phytochemical investigation of the lg/mL). (Ref: Bioorganic & Medicinal Chemistry Letters, active extracts led to the isolation of three new 2008, 18, 4015ñ4017) prenylated isoflavones, isoscandinone, scandenin A and Hedychium spicatum is a plant belonging to the family scandenin B in addition to scandenone, scandinone Zingiberaceae. Medicinally, the rhizomes of the plant and 4í, 5í, 7-trihydroxybiprenylisoflavone as the main are used for the treatment of a number of ailments. The constituents, having α-glucosidase enzyme inhibitory CHCl3 extract of the rhizomes of the H. spicatum and free radical scavenging properties. A reversed-phase showed cytotoxic activity against the Colo-205 (Colo-

Biennial Report 2007-2009 11 Natural Products

cancer), A-431 (skin cancer), MCF-7 (breast cancer), formulations and Bhasmas used in Traditional systems A-549 (lung cancer) and Chinese hamster ovary cells of medicine such as Ayurveda and their safety and (CHO). Column chromatography studies led to isolation toxicology characteristics. of two new labdane diterpenes along with other compounds. The two new diterpenes and other isolates • Quality Assurance and validation of some ayurvedic showed moderate cytotoxicity on the tested cell lines. formulation for life-style related and gynecological (Ref: Bioorganic & Medicinal Chemistry Letters, 2009, disorders (Sponsored by DST/IICT/IMPCL) 19, 192ñ195) • Studies on the bioavailability, toxicity, safety and APPLIED RESEARCH characterization of Bhasmas produced by traditional • and modern manufacturing processes (Sponsored Isolation of the Two Major Compounds namely by DST/IICT/IMPCL) Licoricidine and Licoroisoflavan A (Sponsored by Colgate-Palmolive Ltd, USA) • Golden Triangle Partnership project on Licoricidine and Licoroisoflavan A have been isolated Standardization of Ayurvedic formulations and from the Licorice extract in 50g and 10g quantities with chemical analysis, Toxicity/safety studies on >99% purity and supplied to sponsor. Bhasmas (Sponsored by CSIR/AYUSH/ICMR): • New Bioactive Molecules for Drug Applications • National Facility for Combinatorial Natural Products Efforts are underway to find suitable industrial partners (Sponsored by DST/IICT): for further development of existing molecules for The proposed mol bank is designed to store 500, 000 therapeutic areas such as anti-cancer, antiulcer etc. compounds and the sample retrieval is carried out using OA-5, a single molecule isolated from Oroxylum indicum the advanced robotic technology. The facility is expected is patented for treatment of gastrointestinal toxicity, to be ready by 2010. associated symptoms and ulcers; and licensed to M/S IPCA Laboratories, Mumbai.

• Toxicity Studies of Herbal Formulations The main objective of these projects are to study chemical standardization of Medicinal Plants, their Proposed robotic sample storage facility

12 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

BASIC RESEARCH furnish annulated pyrrole derivatives relatively in good to high yields. The use of InCl in combination with • 3, • Stereoselective Total Synthesis of Amphidinolide water, makes this procedure quite simple, more T1 convenient and environmentally friendly (Journal of A highly stereoselective total synthesis of amphidinolide Organic Chemistry 2008, 73, 3252-3254). T1 is achieved using Sharpless asymmetric epoxidation, • Gold(III) Chloride Catalyzed Three-Component base induced epoxide opening, chemoselective Reaction: A Facile Synthesis of Alkynyl Derivatives reduction followed by allylation, Evans methylation, base- of 1,2-Dihydroquinolines and Isoquinolines induced reductive elimination, umpolung reaction, chemoselective oxidation, and regioselective Gold (III) chloride is found to be an effective catalyst for macrolactonization (Org. Lett. 2009, 11, 1705-1708) the addition of alkynes on activated quinoline/ isoquinolines to produce a series of alkynyl substituted 1,2-dihydroquinolines and isoquinolines in a single-step operation. The easy availability of starting materials, convenient synthetic procedure, operational simplicity and high regioselectivity makes this strategy very useful for the preparation of enyne derivatives of aza-aromatic compounds (Journal of Organic Chemistry 2008, 73, 6857-6859). • Stereoselective Total Synthesis of Bistramide A highly stereoselective and convergent total synthesis of bistramide A is described. The salient feature of this synthesis is the construction of the spiroketal subunit by hydrolysis of dialkylated tosylmethyl isocyanide derivative derived via alkylation of TosMIC with suitably substituted halohydrin derivatives. (Org. Lett. 2007, 9, 4587-4589). • Heteropoly Acid-Catalyzed Aza-Prins Cyclization: An Expeditious Synthesis of 4-Hydroxypiperidines 4-Hydroxypiperidines are prepared in good yields and with high selectivity by means of aza-Prins-cyclization using 10 mol% phosphomolybdic acid under mild reaction conditions. This is the first report on the preparation of 4-hydroxypiperidines via aza-Prins- cyclization (Tetrahedron Lett. 2009, 50, 1799-1802).

• Three-component Reaction of Aldose Sugars, Aryl Amines and 1,3-Diones: A Novel Synthesis of • Enantioselective Reduction of 2-Substituted Annulated Pyrroles Tetrahydropyran-4-ones using Daucus carota Plant Cells

Aldose sugars undergo smooth coupling with enamines, generated in situ from aryl amines and 1,3-diketones,

in the presence of 10 mol% of InCl3 in water at 80 C to

Biennial Report 2007-2009 13 Synthetic Organic Chemistry & Drug Intermediates

Enzymatic reduction of 2-substituted tetrahydropyran- Emmons olefination as the key steps starting from 4-ones with Daucus carota, plant cells as biocatalyst commercially available p-hydroxy benzaldehyde in 12 occurred in water under extremely mild and steps with 14.7% overall yield (Tetrahedron Lett. 2008, environmentally benign conditions giving a 1:1 mixture 49, 5590-5592). of diastereoselectively (2R,4S)- and (2S,4S)-2-aryl- or 2-alkyl-tetrahydropyranols in high yields (Tetrahedron Lett, 2008, 49, 2768-2771).

• Modular Total Synthesis of Lamellarin G Trimethyl Ether A modular synthesis of the lamellarin G trimethyl ether has been developed based on the application of several • reaction sequences which include Friedel-Crafts Stereoselective Total Synthesis of Synparvolide B acylation, esterification, haloarylation and oxidative and epi-Synparvolide A cyclisation.The formation of pyrrolo [2,1-a]isoquinoline Stereoselective total synthesis of synparvolide B and core which happens to be the key step for the epi-synparvolide A has been achieved following a successful completion of Lamellarin G trimethyl ether convergent approach. Synparvolide B is a constituent synthesis is comfortably accomplished through the from extracts of leaves of the plant Syncolostemon haloarylation which results in exclusive endo product parviflorus which is known to be used as an emetic to (Synlett 2009, 43-46). treat loss of appetite. Noyori asymmetric Transfer Hyderogenation of ketone and Wadsworth-Emmons olefination reaction are the key steps involved (Tetrahedron Lett. 2009, 50, 2420-2424).

• A convergent Approach for the Total Synthesis of (-)-Synrotolide diacetate • A Concise Stereoselective Total Synthesis of A simple carbohydrate based convergent approach Herbarumin III towards the total synthesis of (-)-synrotolide diacetate A stereoselective total synthesis of the phytotoxic is described employing a Sharpless asymmetric compound herbarumin III has been achieved in eight epoxidation, a Grignard assisted lactol opening with a steps in 16% overall yield utilizing Crimmins aldol terminal alkyne and a Wittig reaction using Horner- approach, 1,3-syn asymmetric reduction and an olefin Emmons reagent as the key steps (Tetrahedron Lett. metathesis reaction as the key steps (Synthesis 2008, 2007, 48, 6977-6981). 1938-1942).

• Mediated Alkynylation of Carbonyl Compounds with Iodoalkynes: A Facile Synthesis of Propargyl • First Stereoselective Total Synthesis of (+)- . Dodoneine The First stereoselective total synthesis of the natural product (+)- dodoneine is described involving a Crimmins aldol reaction and a Horner-Wadsworth-

14 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

A straight forward synthesis of propargyl alcohols from A practical and enantioselective total synthesis of

alkynyl iodides and carbonyl compounds using zinc is Hyacinthacine A1 (Glycosidase inhibitor) is achieved described illustrating 13 examples (Tetrahedron Lett. involving syn allylic epoxide opening with retention using 2008, 49, 7132-7134). Pd catalysis and ìdominoî hydrogenation (5-steps in one-pot) sequences (J. Org. Chem. 2008, 73, 7826- • The Concise Synthesis of a Key Intermediate for 7828) the Total Synthesis of Fumagillin, TNP-470 and • Ovalicin. Spirastrellolide B: The synthesis of Southern (C9-

The facile synthesis of a key intermediate for the total C25) Region synthesis of the antiangiogenic compound fumagillin, A combination of ìchironî and ìasymmetricî approaches its semisynthetic analogue TNP-470, and ovalicin is is utilized to construct the southern (C9-C25) region of described using a Diels-Alder strategy and a zinc marine natural product spirastrellolide B. The key mediated ring opening reaction to realize the functionalities are derived from D-glucose and Sharpless cyclohexane backbone (Synthesis 2008, 1460-1466). asymmetric epoxidation and dihydroxylation (Org. Lett. 2008, 10, 4355-4357).

• Asymmetric Synthesis of (+)-Passifloricin A and its 6-Epimer Stereoselective total syntheses of the antiprotozoal natural product (+)-passifloricin A and its C-6 epimer have been achieved in ~5% overall yield. The strategy is based on Jacobsen epoxidation, Grubbsí metathesis and an Evansí intramolecular oxa-Michael reaction (Tetrahedron Lett. 2008, 49, 4476-4478). • β-Sugar Aminoxy Peptides as Rigid Secondary Structural Scaffolds Short homo-oligomers of a new building block, cis-β2,3- furanoid sugar aminoxy acid, are designed, characterized, and found to exhibit rigid ribbon-like secondary structures composed of 5/7 bifurcated intramolecular hydrogen bonds (J. Org. Chem. 2008, 73, 9443-9446)

• Total Synthesis of Hyacinthacene A1, A Glycosidase Inhibitor

• Total Synthesis of Azumamide E and Sugar Amino Acid Containing Analogue An efficient and practical total synthesis of marine

Biennial Report 2007-2009 15 Synthetic Organic Chemistry & Drug Intermediates

cyclic tetrapeptide, natural product azumamide E (1) is An efficient and operationally simple method for C3- achieved via high-yielding reactions. The strategy also alkylation of 4-hydroxycoumarins has been developed allowed us to synthesize the azumamide E-SAA (sugar under acidic medium giving good yields of the products. amino acid) analogue (2), whose solution-phase NMR In the present method, a reusable AmberliteÆ IR-120 and biological activity studies were also carried out (J. (H+ form) was used as an acid catalyst and secondary Org. Chem. 2009, 74, 401-404). benzyl alcohols were used as alkylating agents. The obtained 3-alkylated-4-hydroxy coumarins offered an easy access for the synthesis of 3, 4-disubstituted coumarins by way of Pd-catalyzed coupling reactions (Tetrahedron 2008, 64, 11666-11672).

• Titanium Tetrachloride Mediated Reductive Ring Opening of C-aryl Pseudoglycals • An Efficient Total Synthesis of (+)-Cladospolide C A facile reductive ring opening of C-aryl pseudoglycals The asymmetric synthesis of (+)-Cladospolide C has is reported for the first time. The combination of titanium been achieved in 11 steps with 26% overall yield. Key tetrachloride (Lewis acid) and triethylsilane (reducing steps in the sequence involve KAPA-promoted alkyne agent) at -78 oC in is a mild and efficient Zipper reaction, TPP-promoted enyne ester (ynoate) to reagent system for this transformation. The reagent diene ester (dienoate) isomerization, Sharpless system was successfully tested on various C-aryl asymmetric dihydroxylation and Yamaguchi pseudoglycal substrates to yield the corresponding ring macrolactonization (Tetrahedron Lett. 2009, 50, 2478- opened products containing two asymmetric hydroxyls 2580). and a cis-double bond (Tetrahedron Lett. 2008, 49, 863- • Stereoselective Synthesis of Simplactone B via 866). Prins Cyclisation Stereoselective synthesis of Simplactone B, an important class of bioactive ‰-lactones, was achieved through a series of nine steps in 85% overall yield utilising Prins cyclisation and PCC mediated over oxidation as the key steps starting from (R)-benzyl glycidyl ether. (Tetrahedron, 63, 11011, 2007)

• Asymmetric Synthesis of (-)-6-epi-Centrolobine Stereoselective total synthesis of (-)-6-epi-centrolobine, an unnatural analogue of (-)-centrolobine, starting from readily available tri-O-acetyl-D-glucal has been described for the first time. The key steps involved in this synthetic approach are stereoselective C-glycosidation, • Synthesis of Enantiopure Bicyclic Azetidines dehydroxylation and Wittig reaction. The target molecule was achieved in nine steps with 49% overall yield (Synthesis 2008, 2939-2942).

Enantiopure 1-azabicyclo[3.2.0] heptane derivatives were synthesised from the enantiomerically pure epoxides • Solid Supported Acid-catalyzed C3-Alkylation of 4- and L-proline. The key step of the synthesis relied on Hydroxy Coumarins with Secondary Benzyl the diastereo selective intramolecular alkylation of proline Alcohols: Access to Synthesis of 3, 4-Disubstituted enolate which led to an azetidine ring fused to five Coumarins via Pd-coupling membered ring. These strained bicyclic azetidines were

16 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

found to be good precursors for the preparation of • Copper Oxide Nanoparticle Catalysed Coupling of azepanes. (Eur. J. Org. Chem., 34, 5734, 2007) Diaryl Diselenide with Aryl Halides under - free Conditions • Supramolecular Synthesis of Selenazoles using Selenourea in Water An efficient and ligand-free cross-coupling reaction of aryl halides and diaryl diselenides was achieved using The reaction of air and light sensitive selenourea with nanocrystalline copper oxide as recyclable catalyst and -bromo ketones was carriedout for the first time in KOH as the base. This protocol has been utilized for water under supramolecular catalysis in the presence the synthesis of a variety of aryl selenides in excellent of ‚-cyclodextrin to get selenazoles in high yields. (J. yields. (Org. Lett., 11, 951, 2009) Org. Chem., 72, 1849, 2007) • Supramolecular Synthesis of 3-indolyl-3- hydroxyoxindoles under Neutral Conditions in Water Various 3-indolyl-3-hydroxyoxindoles were prepared for the first time by supramolecular catalysis involving the reaction of ‚-CD:isatin complexes with indoles under • Designer Molecules from Sugar Amino Acids and neutral conditions in water. The reaction otherwise yields other Scaffolds: 3,3í-biindolyl oxindoloes under normal conditions. (J. Synthesis and structural studies of peptides Org. Chem., 73, 1646, 2008) containing a mannose-derived furanoid sugar amino acid A mannose-derived furanoid sugar amino acid (Maa) induced helical turns in peptides having repeat units of

Maa(Bn2)-Phe-Leu, which aggregated into head-to-tail duplexes in the longer oligomers (Org. Biomol. Chem. 2007, 5, 3713ñ3716).

• Chiral Discrimination of Tolterodine Tartarate by Modified Cyclodextrins The chiral discrimination ability of two β-cyclodextrin derivatives (hosts) having a flexible pyrrolidinylidenesulfamido-appended moiety has been studied for the enantiomers of zolmitriptan and tolterodine tartarate using fluorescence as the signaling option. These CD derivatives act as artificial receptors, wherein the guest displaces the appended moiety from inside to the outside of the CD cavity and this • Furan based cyclic oligopeptides selectively target phenomenon was studied by observing the change in G-quadruplex fluorescence. The S-enantiomer of the drugs was better recognized than the R-enantiomer. (Helv.Chim.Acta., 90, 1697, 2007, J. Carbohydrate Chem., 27, 223, 2008)

Biennial Report 2007-2009 17 Synthetic Organic Chemistry & Drug Intermediates

The binding properties of 18- and 24-membered cyclic oligopeptides developed from a novel furan amino acid, 5-(aminomethyl)-2-furancarboxylic acid, to G-quadruplex were analyzed. Comparative analysis of the binding data of these ligands with G-quadruplex and double- strand DNA showed that 24-membered cyclic peptides are highly selective for telomeric G-quadruplex structures and thus can be used as a scaffold to target quadruplex structures at the genomic level. (J. Med. Chem. 2007, 50, 5539-5542).

• Design of a ëNew Motifí with β-Amino Acids and α- Aminoxy Acids: Synthesis of Hybrid Peptides with 12/10-Helix Hybrid peptides are prepared from a C-linked carbo-β- • Total Synthesis of Cruentaren B amino acid ester (R-β-Caa) and an α-aminoxy acid (R- A convergent total synthesis of the cytotoxic natural Ama) derived from S-. Extensive studies product cruentaren B has been completed in 26 steps (NMR, CD and MD) on the tetra- and hexapeptides led (longest linear sequence) with an overall yield of 7.1%. to identification of robust 12/10-mixed helices and the (J. Org. Chem. 2008, 73, 3578-3581). the dipeptide repeat having an R-β-Caa and an R-Ama, as a ënew motifí. The further studies revealed the side chains of monomers have profound influence on the stability of the helix (J. Org. Chem., 2008, 73, 3689).

• Highly Enantioselective Carbon-Carbon Bond Formation by Cu-catalyzed Asymmetric [2,3]- Sigmatropic Rearrangement: Application to the Syntheses†of†Seven-membered Oxacycles and Six- membered Carbocycles • Three Residue Turns in α/β-Peptides and their Application in the Design of Tertiary Structures A new three residue turn was serendipitously discovered in α/β-hybrid peptides derived from alternating C-linked carbo-β-amino acids (β-Caa) and L-Ala residues. The three residue ëβ-α-βí turn at C-termini, nucleated by a helix at the N-termini, resulted in helix-turn (HT) super A concise route was developed for the syntheses of secondary structures in these peptides. Further, the enantioenriched functionalized scaffolds of medium sized HT motifs were efficiently converted, by an extension oxacycles and carbocycles empolying a chiral auxiliary with helical oligomers at the C-termini, into peptides mediated Cu-catalyzed ylide formation / [2,3]- with novel helix-turn-helix (HTH) tertiary structures. sigmatropic rearrangement as a key step. This Extensive NMR studies were carried out to delineate methodology was successfully applied for the synthesis the secondary and tertiary structures in these peptides, of carbocyclic analogues based on oseltamivir which were further supported by the molecular dynamics phosphate, an important anti-influenza drug as motif. (MD) investigations (Chem. Asian J., 2008, 3, 969). (Chem. Commun. 2008, 5324)

18 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

• Enantioselective total Synthesis of Eicosanoid and cascade reaction sequence of methylenation, clevage its Congener using Organocatalytic of isopropyl group, carbocyclization and again Cyclopropanation and Catalytic Asymmetric methylenation (Chem. Commun. 2008, 3423). Transfer Hydrogenation Reactions as Key steps An enantioselective unified strategy for the syntheses of the oxylipin class of natural products was accomplished. Our strategy relies on three catalytic steps a) organocatalytic cyclopropanation b) catalytic • Application of Self-metathesis in the Synthesis asymmetric transfer hydrogenation (CATHyTM) reaction 1,6-dioxaspiro(4,5)decane spiroketal using C2- c) Nozaki-Hiyama-Kishi reaction. (J. Org. Chem. 2008, Symmetric Approach 73, 5198-5201). A common asymmetric approach for the synthesis of 1,6-dioxaspiro(4.5)decane chiral spiroketal system, which is a subunit of various natural products is • Stereoselective synthesis of 1,4-dideoxy-1,4-imino- described and the key aspects of the synthesis are derivetivies of D-allitol, L-allitol and D-talitol self- crossmetathesis and exploitation of C2- symmetric A stereo selective approach for azasugars 1,4-dideoxy- of the metathesis product to get required chiral 1,4-imino-D-allitol, L-allitol and 1,4-dideoxy-1,4-imino- spiroketal.( Tetrahedron asym.2008, 19, 1820). D-talitol was described from (R)-2,3-O-isopropylidine glyceraldehyde, L-ascorbic acid and D-isoascorbic acid by using vinyl Grignard addition on chiral imine, allylation, RCM and dihydroxylation as the key steps.(Tetrahedron 2007, 8746) • The Formal Synthesis of Isofebrifugine using Stereo selective Intramolecular Michael addition Synthesis of isofebrifugine via stereoselective Michael addition, taking advantage of the stable conformation of C-2 substituted N-acyl piperidines (Tetrahedron Asymmetry 2008, 19, 2153). • A Short, Efficient and Stereoselective Total Synthesis of Pyrrolidine Alkaloid: (-)-codonopsinine An efficient total synthesis of antibiotic (-)-codonopsinine with an overall yield of 44% was achieved from D- alanine as a chiral template. The key steps in our • A Concise Enantioselective Strategy to (R)-(+)- strategy are modified Sharpless asymmetric Goniothalamin and (R)-(+)-goniothalamin Oxide dihydroxylation reaction and the highly stereoselective by Employing Hydrolytic Kinetic Resolution and intramolecular acid catalysed amidocyclisation (J. Org. RCM as Key Steps Chem. 2007, 72, 2224).

An efficient and general strategy to (R)-goniothalamin and (R)-goniothalamin oxide is described by using • Carbohydrates to Carbocycles: a novel Approach Jacobsenís hydrolytic kinetic resolution of racemic to Carbafuranoses via Tebbe mediated Cascade epoxide and ring closing metathesis (RCM) as key Reactions steps which provided a rapid access to these natural A new, efficient and highly diastereoselective approach products that display fascinating array of biological for the synthesis of 1,2,3,5-tetraacetylcarba-a-D- activities. (R)-goniothalamin oxide was prepared in high lyxofuranose 1 from D-ribose is reported via one pot yield and diastereomeric excess under various conversion of 2 to 3 using Tebbe reagent which involves epoxidation conditions (Synthesis 2008, 2323-2326).

Biennial Report 2007-2009 19 Synthetic Organic Chemistry & Drug Intermediates

• Total Synthesis of (-)-Bitungolide F and dihydro-2H-pyran-2-one 2, is one such natural product Determination of its Absolute Stereochemistry which was isolated from Ravensara crassifolia. The A highly convergent total synthesis of bitungolide F first stereoselective total synthesis of 2 through ring- leading to the assignment of its absolute opening reaction of chiral epoxide, obtained by an stereochemistry is described. (J. Org. Chem. 2008, iterative Jacobsenís kinetic resolution protocol with the 73, 1582 -1585). known chiral propargyl and elaboration of the ensuing triol to the target compound was accomplished and reported (Tetrahedron Letters 2007, 48, 2015-2017).

• First Total Synthesis of Emericellamide A A stereoselective synthesis of (6S)-5, 6-dihydro-6-[(2R)- A highly convergent asymmetric total synthesis of 2-hydroxy-6-phenylhexyl]-2H-pyran-2-one 3, was emericellamide A, a 19-membered antibacterial achieved through the olefin cross-metathesis strategy depsipeptide isolated from the co-culture of an as the key step (Tetrahedron: Asymmetry 2007, 18, Emericella sp. (strain CNL-878) and a Salinispora 2197-2200). arenicola (strain CNH-665) is described. (Tetrahedron Lett. 2008, 49, 3697-3700).

• Stereoselective Total Synthesis of 10-Membered macrolides The impressive biological profile of macrolides 4 and 5, coupled with their structural features attracted our attention as valuable synthetic targets. Total synthesis • of (-)-aspinolide B 4 (Synthesis 2007, 3627-3634) and Synthesis of 6-Substituted-pyran-2-one Containing first synthesis of macrolide 5 (Synlett 2008 In Press) Natural Products was accomplished recently.

• Synthesis of Nitrogen Containing Natural Products We recently embarked on a program towards the Stereoselective total synthesis of synrotolide as its synthesis of piperidine-containing bio-active natural diacetate 1a from D-ribose utilizing a diastereoselective products, and in this connection, herein a formal total Grignard reaction, preferential (Z)-Wittig olefination, synthesis of (+)-hyperaspine 6 is reported, wherein a asymmetric allylation and ring-closing metathesis as novel one-pot, double aza-Michael reaction is utilized key steps is reported (Tetrahedron 2007, 63, 3995-3999). as the key reaction for construction of the important piperidinone ring-skeleton (Tetrahedron Letters 2007, (6R)-6-[(4R,6R)-4,6-Dihydroxy-10-phenyldec-1-enyl]-5,6- 48, 6924-6927).

20 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

• Ring Closing Metathesis as an Efficient Protocol for the Stereoselective Synthesis of Spiro C-linked A ring-closing metathesis approach was adopted to 4-deoxy Disaccharides construct the piperidine ring while Sharpless asymmetric Ring Closing Metathesis protocol on bis-allylic chirons epoxidation was used for generating two contiguous derived from sugars was utilized for the stereoselective stereocenters efficiently as the key strategy for the synthesis of spiro C-linked deoxy disaccharides. Uloses total synthesis of (2R,2íR)-threo-(+)- 7, derived from D-xylose and L-sorbose were converted commonly known as Ritalin (Synlett 2007, 1742-1744). into bis-allylic derivatives, which on RCM gave the spiro enone rings. The xylose-derived spiro-enone on sequential oxidations was converted into new deoxy spiro C-disaccharides (Lett. Org. Chem., 2008, 5, 465).

• RCM Mediated Synthesis of Macrosphelides I and G Total synthesis of 16-membered macrolides, macraosphelides I and G, has been achieved starting • from ethyl-(S)-lactate and (S)-malic acid. A combination Stereoselective Synthesis of Carbon-carbon Linked of Jacobsenís hydrolytic kinetic resolution and Deoxy Disaccharides Sharpless epoxidation is used for the creation of two Synthesis of C(4)-C(5)-linked furano-deoxy pyranosides stereogenic centers, while Yamaguchi esterification and and C(5)-C(6)ñ linked pyrano-deoxy pyranosides is ring-closing metathesis strategies were used for the reported from D-glucose and D-galactose respectively. construction of the lactone ring (Tetrahedron Asymm., The chirons derived from the monosaccharides impart 2007, 18, 2175). the chirality to the newly constructed deoxy saccharides (Synthesis, 2007, 2700).

• Attempts Towards the Synthesis of Feigrisolide B • Total Synthesis of Patulolide C and Feigrisolide B is a seven membered ring lactone. It 11-Epipatulolide C exhibited strong atnibaacterial, antiviral and anticancer Total synthesis of 12-membered macrolides, patulolide activities. Synthesis of lactones 3 and 4 is reported in C, 11-epipatulolide C and formal synthesis of patulolide an attempt towards the synthesis of natural product A and epipatulolide A, starting from 1,8-octane diol is feigrisolide B. Sharpless asymmetric epoxidation and reported. A combination of Jacobsenís hydrolytic kinetic Gillman epoxide opening reactions were used for the resolution and Sharpless epoxidation is used for the construction of the required frame work containing two creation of two stereogenic centers, while ring-closing streocentres. The synthesis of lactones 3 and 4 revealed metathesis strategy was used for the construction of that the proposed structure for feigrisolide B is incorrect the lactone ring (Tetrahedron Asymm., 2008, 19, 577). (Lett. Org. Chem., 2007, 4, 110).

Biennial Report 2007-2009 21 Synthetic Organic Chemistry & Drug Intermediates

(RCM) protocol is envisioned as a means of ready access to sugar-linked α, β-unsaturated-γ-lactone library of compounds (J. Comb. Chem., 2007, 9, 62-69).

SYNTHETIC METHODOLOGIES • TosMIC Mediated: A diastereoselective three-component Passerini reaction (P-3CR) of chiral 2,3-epoxy aldehydes with tosylmethyl isocyanide (TosMIC) under conditions was evaluated to afford densely substituted products (Synlett 2007, 83-86). Similarly, the olefin from the Baylis-Hillman adducts of N-allyl aminals were used in RCM reaction to generate functionalized chiral tetrahydropyridines library of compounds (29a-d and 29aí-dí) which were functionalized further into their corresponding azasugar derivatives 30a-d and 30aí-dí (J. Comb. Chem., 2008, The synthesis of oxazole and pyrrole 3-carbethoxy/3- 10, 426-435). arylsulfonyl D and L-2-deoxyribosides by TosMIC addition/cyclization on D and L-2-deoxyribo-1- carboxaldehyde and unsaturated esters in moderate to good yields is reported (Tetrahedron 2007, 63, 9871- 9880).

InCl3 mediated C-C coupling reaction between aryl alcohols and TosMIC afforded the corresponding amides Also, the olefin emanating from the Baylis-Hillman in good to high yields (Tetrahedron Letters 2007, 48, adducts of acyclic sugar-derived aldehydes was 9048-9050). conceived as the masked ketone/hydroxyl functionality and used as a strategic tool for the synthesis of higher- carbon sugars (Tetrahedron Letters 2007, 48, 6466- 6470).

Lewis acid and/or Lewis base mediated [3+2]- cycloaddition reaction of activated olefins, including • Baylis-Hillman Reaction Baylis-Hillman adducts with ethyl diazoacetate gave A combination of Baylis-Hillman reaction, which the corresponding pyrazolines (Tetrahedron Letters 2008, produces an olefin en route, and ring-closing metathesis 49, 6768-6772).

22 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

• Synthesis of 2-arylbenzothiazoles via DDQ promoted cyclization of thioformanilides - a solution phase strategy for library synthesis Several substituted benzothiazoles are synthesized via the intramolecular cyclization of thioformanilides using

DDQ in CH2Cl2 at ambient temperature in high yields. The resulting 2-arylbenzothiazoles were separated from the reduced DDQ byproduct by treatment of reaction mixture with a strongly basic ion-exchange resin. This protocol offers a high degree of flexibility with regard to the functional groups that can be placed on the benzothiazole ring or 2-aryl moiety which in turn • A Convenient Access to Substituted Benzothiazole generates scaffolds for parallel synthesis (Synthesis Scaffolds via Intramolecular Cyclization of 2007, 819-823). Thioformanilides A new and practical method has been developed for the synthesis of substituted benzothiazoles via the intramolecular cyclization of thioformanilides using DDQ

in CH2Cl2 at ambient temperature. The reaction prooceeds in high yields via the thiyl radical to give novel oxybis-benzothiazole, and offers a high degree of flexibility with regard to the functional groups that can be placed on the benzothiazole nucleus or 2-aryl moiety which in turn generates scaffolds for parallel synthesis • An efficient method for the alkylation of (Tetrahedron Lett., 2007, 48, 669-672). halonitrobenzenes with malonates assisted by microwave-irradiation An efficient synthesis of Flurbiprofen has been reported, via aromatic nucleophilic displacement reaction.The key • intermediate diethyl 2-methyl-2-(3-fluoro-4-nitrophenyl) An Efficient and High Yielding Protocol for the malonate was easily prepared from commercially Synthesis of Substituted Dihydropyrimidin-2(1H)- available starting material 2, 4-difluoronitrobenzene in ones and Spiro-fused Heterocycles by involving presence of microwave irradiation The para substituted Tandem Reactions product on further transformation of diazotization followed A simple and efficient method has been developed for by coupling gave the required anti-inflammatory drug the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by a Flurbiprofen. (Catalysis Letters, 2008, 121, 81). one-pot three component cyclocondensation reaction of alkyl acetoacetates, aldehyde, and urea in the presence of a catalytic amount of reusable catalyst

Zinc per chlorate hexahydrate, Zn(ClO4)2.6H2O (10 mol %) the scope of this protocol is utilized for the synthesis of mitotic Kinesin EG5 inhibitor and new class of fused heterobicyclic compounds in high yields (J. Heterocyclic. Chem., 2007, 44, 211-214).

Biennial Report 2007-2009 23 Synthetic Organic Chemistry & Drug Intermediates

• LaCl3 accelerated conjugate addition of amines to show that thermal decomposition occurred in steps electron-poor alkenes. that depended entirely on the chemical compositions A simple and efficient method for 1, 4-addition of amines and the synthesis routes. SEM observation reveals that to ‚-ethylenic compounds has been reported using the morphology and particle size strongly depend on trichloride as catalyst. This method is synthesis routes for their precursors (Chinese J. Chem. successfully applied for the conjugate addition of a 2007, 25, 998). variety of amines to , ‚-unsaturated esters or nitriles. • Optical properties of Er-doped Al2O3ñSiO2 films The reactions were carried out at room temperature, prepared by a modified SolñGel process the reaction conditions are very mild and the isolation Er-doped Al O ñSiO (1/9 in mol ratio of Al O /SiO ) thin of products very easy (Lett. Org. Chem. 2007, 462). 2 3 2 2 3 2 films were prepared by using a modified solñgel process. The modified process entails the precipitation and

digestion of Er(OH)3, obtained from the reaction between

Er ions and NH4OH in solution. Thin films were • deposited on Si wafers by using a spin coating • Design of nanosynthesis based on precursor technique (3000 rpm) and the coated films were heat chemistry treated at different temperatures for 1 h in an oxygen- Photoluminescence characteristics of SolñGel purged furnace. All the films were structurally materials prepared from bimetallic erbium characterized by the X-ray diffraction technique using alkoxides coordinated by Al or Ti CuK radiation. The luminescence properties of the Er- 3+ doped Al O ñSiO made by a conventional and our Er -doped Al2O3ñSiO2 and TiO2ñSiO2 powders were 2 3 2 prepared by the solñgel process using bimetallic erbium modified doping process were compared and discussed isopropoxides coordinated with Al or Ti. The local from the stand point of peak intensities and lifetimes environment surrounding Er3+ ions were controlled orderly as a function of annealing temperatures. It is to be at the precursor stage. The phase development of two noted here that our modified process was found to be different systems as a function of temperature was more effective in reducing the clustering of Er ions in characterized by XRD, and the amount of OH groups Al2O3ñSiO2 materials as compared to that of the remaining within the samples was investigated by a FT- conventional method (J. Am. Ceramic Soc. 2007, 88, IR. The photoluminescence spectra and lifetimes of 2380). two systems annealed at different temperatures were • Design, Synthesis and Use of Novel Chiral Amine measured and discussed. (J. Am. Ceramic Soc. 2007, Catalysts for Enantioselective Baylis-Hillman 90, 116). reaction: Utility of the Adducts as Versatile • Cerium alkoxides - synthesis, properties and their Polypropionate Stereotriads use in Michael addition reaction Cerium(III) alkoxides served as an effective and attractive promoter for the Michael addition reaction with excellent chemical yields under mild conditions in short reaction time (Chinese J. Chem. 2008, 26, 751). • Synthesis and characterization of fluoro- and chloro-bimetallic alkoxides as precursors for luminescent metal oxide materials via Sol-Gel technique Novel and new series of bimetallic alkoxides has been prepared by metathesis route. They exhibit a lower sensitivity towards hydrolysis and so they are easier to handle as compared to other alkoxides. All the compounds were characterized by elemental analysis, FT-IR and multinuclear NMR spectroscopies. The mass spectra show similar types of fragmentation pattern. SEM-EDS analyses showed consistency with the formulation. XRD patterns show an enhanced homogeneity at high temperature. TGA measurements

24 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

Several chiral amines based on morpholine, piperizine them have different limitations. Therefore, this leads to and others were identified as promising candidates. explore the development of new efficient and practical After having accessed them, these catalysts were methodologies. screened for Baylis-Hillman reaction. The results are A large number of new synthetic strategies involving tabulated. oxidative, reductive and deprotective cylizations have Further work on the refining the catalyst design, been accomplished. These have been achieved by synthesis and their use is under progress. Utility of employing different types of reagents such as TPAP/

adducts is also underway (1). Tetrahedron Lett. 2007, MNO, HMDST, TMSCl/NaI, SmI2, Bi(OTf)3.XH2O and HI. 48, 6466-6470. 2) J. Comb. Chem. 2008, 10, 436-441. By the development of such new methods it became 3) Synlett 2008, 2897-2912). possible to synthesize this ring system and its analogues in an efficient manner, thus leading to a • Synthesis of densely functionalized carbocycles significant number of NCEís from which a number of from carbohydrates: Design of approaches to lead compounds emerged. synthesize some important carbocyclic polyols • Carbocyclic polyols are important bioactive molecule. • Design of novel DNA-binding molecules Most of the compounds in this category are poly Furthermore, a research programme aimed towards the hydroxyl cyclopentane and cyclohexane skeletons and design of new type of pyrrolobenzodiazepines led to some of their amino derivatives popularly called as the discovery of potent anticancer compounds with aminocarba sugars. Due to the lack of easily remarkable DNA binding affinity. This exercise also gave hydrolysable glycosidase function and their similarity further insights into the structure activity correlations with monosaccharides they may act as enzyme for this important class of compounds. Some of the inhibitors and they have been used as the antibiotics notable examples are the design of novel noncross- and anticancer agents etc. recently a novel methodology linking mixed imine-amide and imine-amine was developed for the conversion of carbohydrates to pyrrolobenzodiazepines. DC-81 dimers have also been carbafuranoses (Chem.Commun., 2008, 3423-3425;) designed by incorporating piperizine moiety in the spacer Synthesis of chiral amines from sugar imines and their chain to enhance the solubility of these compounds. application in the synthesis of amino cyclitols and bicyclic azasugars has been developed: (Tetrahedron Asymmetry, 2009, 1217-1223). DESIGN AND SYNTHESIS OF ANTICANCER DRUGS • Synthesis of DNA binding anthramycin class of compounds Anthramycin, tomaymycin, neothramycin, abbeymycin and DC-81 are the well known examples of pyrrolo[2,1- c][1,4] family of naturally occurring antitumour antibiotics produced by various Streptomyces species. The cytotoxic and antitumour effects of these compounds are believed to arise from modification of DNA, which leads to inhibition of nucleic acid synthesis and production of excision dependent single and double strand breaks in cellular DNA. These antibiotics bind selectively in the minor groove of DNA via a covalent aminal bond between the electrophilic C- 11 position of the PBD and the nucleophilic C-2 amino group of a guanine base, resulting in the observed biological activity. An imine or equivalent functionality at N-10, C-11 position of the ring system is a prerequisite for biological activity. Recently, dimers of this ring system have been designed and synthesized as efficient irreversible DNA interstrand crosslinking agents based on this ring system. There are some reports in literature towards the synthesis of this ring system but most of

Biennial Report 2007-2009 25 Synthetic Organic Chemistry & Drug Intermediates

Novel head to tail dimers of this ring system have also prepared on solid phase by employing different types been designed and synthesized. Moreover a large of approaches and precursors. Moreover, polymer number of hybrids of the pyrrolobenzodiazepines have supported reagents have also been employed for the been designed and synthesized by linking to a variety synthesis of these biologically important moieties, hence of DNA interactive compounds like polyaromatic providing a large libraries of NCEís. [Bioorg. Med. hydrocarbons (pyrene/chrysene), acridines, Chem. Lett. 2008, 18, 2434] anthracinones, naphthalimides, and benzimidazoles • Selective therapy of cancer by ADEPT and PMT through different type and size of alkane chain spacers. strategies Some of these new hybrids have shown excellent DNA β binding ability and promising in vitro anticancer activity. Pyrrolo[2,1-c][1,4]benzodiazepine- galactoside and Few molecules of this type have also been evaluated glucuronide prodrugs with a potential for selective for in vivo anticancer activity and some are undergoing therapy of solid tumors have been developed. detailed pharmacological evaluations. Molecular Interestingly, these prodrugs not only improves the water modeling has been extensively employed during the solubility and stability but as predicted they fulfil the course of the design of these new hybrids. These criteria of selective activation with the selectivity or investigations have provided numerous New Chemical activation factor ranging from 100-400 folds. [Bioorg. Entities (NCEís) that have been taken up for detailed Med. Chem. 2008, 18, 3769; Chem. Med. Chem. 2008, investigations as new lead molecules. 3, 794] • Solid-phase and polymer-supported synthesis of pyrrolo[2,1-c][1,4]

• Synthesis of pyrrolobenzodiazepines, azido/amido reductive cyclization approach A versatile and inexpensive strategy has been developed for the reduction of aromatic azides and aliphatic amides The preparation of small molecules on solid-phase is in one-step leading to intramolecular reductive emerging as an expedient and is being utilized towards cyclization as a convenient route for the preparation of generating compounds for screening against biological imine containing pyrrolobenzodiazepines. systems and enhances the drug discovery effort. In this connection, the development of new solid phase methodologies is an essential component for increasing the range of compounds that could be accessible by this approach. In this context, some practically useful solid phase methodologies have been developed for the synthesis of pyrrolobenzodiazepines. An efficient and mild method for the reduction of aromatic nitro and

azido group on solid support using Al/NiCl2.6H2O and

Al/NH4Cl has been developed and this has been extended for the synthesis of pyrrolo[2,1- c][1,4]benzodiazepines. These compounds have been

26 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

Further, this approach has also been extended towards benzimidazole chromophore was studied by DNA the preparation of PBD. [Tetrahedron Lett. 2008, 49, melting experiments, UV and fluorescence titrations, 1465] CD spectroscopy and isothermal titration calorimetry • (ITC). Binding of both hybrids results in a remarkable Synthesis, DNA-binding affinity and cytotoxicity of thermal stabilization with an increase of DNA melting PBD conjugates temperatures by up to 40 oC for duplexes that allow for A series of molecules based on pyrrolobenzodiazepine a covalent attachment of the PBD moiety to guanine [PBD] conjugates comprising of PBD-anthraquinone, bases in their minor groove. CD spectroscopic benzothiadiazine-PBD, and PBD-diethyl phosphonate measurements suggest that the naphthalimide moiety have been designed and synthesized. These compounds of the drug interacts through intercalation. In contrast, have been evaluated for their cytotoxicity against human the PBD-benzimidazole hybrid binds in the DNA minor tumor cell lines. Some of the compounds have exhibited groove with a preference for (A,T)4G sequences. Whereas promising DNA-binding affinity and anticancer activity the binding of both ligands is enthalpy-driven and in selected human cancer cells. [Bioorg. Med. Chem. associated with negative entropy, the benzimidazole 2007, 15, 6868; Bioorg. Med. Chem. Lett. 2007, 17, hybrid exhibits a less favourable binding enthalpy that 5345; Bioorg. Med. Chem. 2008, 16, 3895; 16, 7804; is counterbalanced by more favourable entropic term Chem. Biol. Drug Design.. 2008, 71, 78; Letters in when compared to the naphthalimide hybrid. Drug Design & Discovery 2008, 5, 261]

Covalent adduct of DC-81 with DNA from C11-position of the PBD to the guanine 2-amino group of a CG base pair. [Bioorg. Med. Chem. 2009, 17, 919] • Synthesis of triazole-PBD dimers by employing ëclickí chemistry and their DNA binding affinity

• Spectroscopic and calorimetric studies on the DNA recognition of PBD hybrids DNA binding of two hybrid ligands composed of an alkylating pyrrolo[2,1-c][1,4]benzodiazepine (PBD) A series of 1,2,3-triazole-containing pyrrolo[2,1- moiety tethered to either a naphthalimide or a phenyl c][1,4]benzodiazepine dimers have been prepared

Biennial Report 2007-2009 27 Synthetic Organic Chemistry & Drug Intermediates

efficiently by employing a ëclickí chemistry protocol. Discovery 2008, 5, 353] This method involves 1,3-dipolar cycloaddition of terminal alkynes with organic azides using a Cu(I)-catalyst. These compounds have been evaluated for their DNA binding affinity using DNA thermal denaturation studies. Some compounds have shown significant DNA binding ability. Detailed studies on the mechanistic aspects, and anticancer activity and molecular modeling investigations on these dimers are in progress. [Bioorg. Med. Chem. Lett. 2008, 18, 1468; Tetrahedron Lett. • Synthesis of Quanoline derivatives and their 2008, 49, 3620] antibacterial activity DESIGN AND SYNTHESIS OF ANTI-INFECTIVES A new method for the synthesis of quinolines has been developed by employing various novel catalysts such • Synthesis of antimycobacterials: as Al(OTf)3, Gd(OTf)3 and TMSCl-NaI. These compounds Tuberculosis is a dreadful disease caused by bacteria are condensed with 3-hydrazino benzothiadiazines to called Mycobacterium tuberculosis and responsible for obtain quinoline derivatives. The new molecules more human deaths than any other single infectious synthesized have been evaluated for their antibacterial disease. It is estimated that, about one-third of the activity and some of them have exhibited significant worldís population is infected with this disease. For antibacterial activity in comparison to sulfadiazine. this reason, there is an overwhelming need to develop [Letters in Drug Design & Discovery 2007, 4, 580] novel antimycobacterial agents with different mechanism of action aimed at a better understanding of antimycobacterial resistance.

• Bis(indolyl) methanes as antimicrobial agents

In continuation to earlier work on benzothiadiazines, a series of nitrofuran, nitrothiophene and arylfuran coupled benzothiadiazins have been prepared and evaluated for antimycobacterial and antibacterial activities. One of the compounds has shown good in vitro antimycobacterial activity. All the synthesized compounds have shown moderate to good antibacterial activity. [Bioorg. Med. Chem. 2007, 17, 5419] • Benzothiazole- benzothiadiazine conjugates as antibacterial agents Indole derivatives are found to exhibit a wide spectrum A new series of benzothiazolo-benzothiadiazine hybrids of pharmacological activities. Bis(indolyl) methane, which have been synthesized and evaluated for their contains two indole or substituted indole units in a antibacterial activity against clinical isolates of Gram- molecule are found in bioactive metabolites of terrestrial positive and Gram-negative bacteria. Some of the hybrids and marine origin and they are found to exhibit a broad in this series exhibited antibacterial activity comparable spectrum biological activities. A versatile and efficient to ampicillin. In addition, some of the compounds method has been developed for the synthesis of these showed DNA gyrase inhibitory activity at a moderate Bis(indolyl) methanes by using aluminum triflate as a level compared to . Similarly a series of novel catalyst. This methodology for the synthesis of compounds based on quinolone - coupled benzothiazoles BIMs using the catalyst process is more advantageous have been prepared and evaluated for their efficiency over earlier methods like mild reaction conditions, as antibacterial agents. [Letters in Drug Design & cleaner reactions, shorter reaction times, high yield of

28 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

products and low catalytic amount. [J. Enzyme Inhibn. The promising cultures are being tested for solvent & Med. Chem. 2008, 1, 7] tolerance, and optimization of reaction parameters. • Substituted benzothiazine derivatives • Value chain model for bioethanol production from A new series of 10-substituted 5,5-dioxo-5,10- sweet sorghum

dihydro[1,2,4] triazolo [1,5,-b]-[1,2,4]benzolthiadiazine Sweet sorghum is a C4 plant with high photosynthetic arylsulfonamide derivatives have been synthesized and efficiency and high biomass production. The stalks have their structures have been confirmed on the basis of the ability to accumulate high amounts of fermentable spectral data, elemental analysis, X-ray analysis and sugars which can act as a potential feedstock for quantum chemical calculations. There compounds are production. Protocols for juice quality evaluated for their efficiency as antibacterial agents assessment have been standardized with respect to against various Gram-positive and Gram-negative strains the estimation of total soluble sugars and reducing of bacteria. Some of the compounds are active against sugars. An HPLC protocol was standardized for Escherichia coli as well as Bacillus subtilis. Other quantification of glucose, fructose and sucrose in sweet compounds also showed potent inhibitory activity in sorghum juice. Around 400 yeasts have been isolated comparison to the standard drugs. [Bioorg. Med. Chem. from diverse sources and screening of these yeast 2007, 17, 5400] isolates for their ability to convert fermentable sugars to bioethanol has been initiated. A plate screening protocol has been standardized for the detection of ethanol production ability due to the alcohol dehydrogenase activity present within the yeasts. • Exploitation of microbial wealth in India In a systematic search program for microorganisms producing bioactive compounds, soil samples were collected from different parts of India. About 1100 BIOTRANSFORMATIONS bacterial cultures isolated from different soil samples were subjected to screening for bioactive compounds This Institute has been actively involved in and nitrilase and enzyme inhibitors. biotransformations/biotechnology processes with a view to develop greener and safer processes/technologies • Process development for ethanol production from catalyzed by enzymes. In continuation to these efforts lignocellulosic biomass towards the synthesis of biologically important Lignocellulosic feedstock is a major inexpensive and compounds, new and simple methodologies have been renewable biomass resource which is available in developed for the synthesis of certain drugs, drug abundance for its bioconversion to biofuels. The intermediates and related molecules for commercially lignocellulosic feedstock is a complex composite of important chiral compounds. three components, namely, cellulose, hemicellulose and • Enzyme tool box lignin. The lignin component acts as a physical barrier and must be removed by suitable pretreatment method Biocatalysis is the greenest technologies for the to release the cellulose and hemicellulose. A lab-scale synthesis of chiral molecules facilitating exquisite delignification process has been optimized and regioselectivity and stereoselectivity under mild developed for different feedstocks such as corn cobs, conditions. Synthetic pathways are designed around sweet sorghum bagasse and cotton stalks. tool boxes of biocatalysts to develop chemoenzymatic routes to meet process requirements on cost efficiency, • Microbial production of biosurfactants waste reduction, minimize energy consumption. Biosurfactants are surface-active metabolites produced Microbial cultures were screened for various enzyme by a diverse range of microorganisms like bacteria, activities with an objective of exploitation of the cultures fungi, yeasts and algae which help to reduce the for structurally or functionally new/novel enzymes and surface and interfacial tensions in both aqueous and create enzyme tool-boxes. More than 1000 cultures hydrocarbon mixtures. They find wide application in were screened for various enzymes like nitrilase, nitrile various industries including microbial enhanced oil- hydratase, epoxidase and lipase. The positive cultures recovery (MEOR), cosmetics, food, beverages, are being utilized for the development of a bioconversion pharmaceuticals, bioremediation, gene delivery system, process for industrially important intermediates. etc. An extensive screening for biosurfactant producing

Biennial Report 2007-2009 29 Synthetic Organic Chemistry & Drug Intermediates

bacteria from oil contaminated soil samples resulted in azidoalcohols are of great interest, owing to their one promising isolate Pseudomonas aeruginosa strain presence in biologically active natural products and their BS-161R which produced metabolites such as application as chiral catalysts in asymmetric synthesis. rhamnolipids and a phenazine antibiotic. These An enantioslective synthesis of chiral γ-azidoalcohols metabolites were further purified and structurally via lipase catalyzed resolution has been developed. characterized and were identified as Rhamnolipid 1 and The efficiency of various lipases and the effect of different Rhamnolipid 2 and a pigment antibiotic, phenazine-1- solvents have been studied. Pseudomonas cepacia carboxylic acid. immobilized on diatomaceous earth (PS-D) in hexane catalyzed the transesterification process in an efficient • Enantioselctive synthesis of (R)-and (S)-curcumene manner providing γ-azidoalcohol in high enantiometric and curcuphenol: excess. The enantiomerically pure γ-azidoalcohols thus A simple and efficient chemoenzymatic route for the obtained by the kinetic resolution in high enantiopurity synthesis of enantiomeric pairs of curcumene and have been utilized towards the synthesis of enantiomeric curcuphenol employing lipase mediated kinetic paris of antidepressant drugs, and . resolution process in high enantiopurity has been [Tetrahedron: Asymmetry 2008, 19, 1078; J. Mol. Cat.B: developed. This protocol also provides an alternative Enzymatic 2009, 58, 132] route for the synthesis of related members of the bisabolene family. [Tetrahedron Asymmetry 2007, 18, 2547]

• Enantiomerically pure β-aminoalcohols Enantiomerically pure β-aminoalcohols are an important class of organic compounds that are present in many biologically significant structures such as aminosugars, antibiotics, β-adrenergic blocking agents, etc. In • Synthesis of enantiomerically enriched (R)-GABOB continuation of our earlier efforts towards the preparation and (R)-carnitine of biologically important compounds or their intermediate by employing lipases, an efficient and flexible γ-Amino-β-hydroxybutynic acid (GABOB) is compound preparation of enantiomerically enriched (R) and (S) of great pharmacological importance because of its enantiomers of timolol has been developed. This biological function as a neuromodulator is the transesterification process has been optimized with mammalian central nervous system. The (R)- form of respect to different lipases and solvents. [J. Mol. Cat. GABOB is shown to have greater biological activity B: Enzymatic 2008, 54, 55] than its S-enantiomer. Moreover, the (R)-isomer of GABOB serves as a precursor for (R)-carnitine, a compound having high level of medical significance.

A methodology employing lipase-mediated resolution of • Synthesis of enantiomerically enriched N-(3-cyano-2-hydroxy propane-1-yl) phthalimide using umbelactones various lipases has been developed and intermediate An efficient and convenient strategy for the enantio- has been utilized towards the synthesis of selective synthesis of enantiomerically enriched enantiomerically enriched (R)-GABOB and (R)-carnitine umbelactones is described utilizing a lipase-mediated in high yields. [J. Mol. Cat.B: Enzymatic. 2007, 47, 1; resolution protocol, Baylis-Hillman reaction and ring Helvetica Chimica Acta. 2007, 90, 1723] closing metathesis as key steps. The lipase-resolution • Resolution of g-azidoalcohols is carried out using several lipases from various sources in different solvents to afford the required intermediate Enantiomerically pure chiral aminoalcohols/ in good yield and high enantioselectivity. [Tetrahedron

30 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

Lett. 2007, 48, 7232] pyrrolobenzodiazepines and their dilactams through intramolecular reductive cyclization process. In this protocol the reagent systems are amenable for the generation of solution-phase combinatorial synthesis. [Synlett 2008, 9, 1297] • Enantioselective synthesis of As a part of the studies directed towards the synthesis DEVELOPMENT OF NEW SYNTHETIC METHODOLOGIES of kavalactones and other biologically active molecules, • an efficient synthesis has been developed for the Acylation of alcohols, and thiophenol under functionalized moieties of these molecules in a suitably solvent-free conditions protected forms employing the Sharpless asymmetric Acylation of alcohols and is an important and dihydroxylation. The enatioselective synthesis of both routinely utilized transformations in organic synthesis. the isomers of dihydrokawain-s-ol is obtained by the Despite a number of precedents, new efficient method. The key features of the synthetic strategy methodologies for acylation are still in demand. A include (a) Sharpless asymmetric dihydroxylation, (b) β methodology using Al(OTf)3 as an efficient and versatile Witting olefination and (c) formation of -keto ester to catalyst for the acylation of alcohols, phenols, thiols, access the highly enantiomerically pure kavalactones. thiophenols and sugars using acetic anhydride under [Tetrahedron: Asymmetry 2007, 18, 1755] solventñfree conditions at room temperature has been developed. The advantages of this method over earlier reported processes include its simplicity, clean and rapid reactions, high yields, and absence of organic solvents, large scale synthesis and retention of chirality. [Tetrahedron Lett. 2007, 48, 3813] • Preparation of β-aminoalcohols β A simple procedure for the preparation of -amino • Baseñfree monosulfonylation of amines using tosyl alcohols employing sulfamic acid as a catalyst has or mesyl chloride in water also been developed under solvent-free conditions. This catalyst is commercial available and in expensive. The Sulfonamides are a diverse group of pharmaceutically easy availability of the catalyst, simple workup important compounds widely used as antibacterial, procedure, solvent-free and mild reaction conditions, anticancer, anticonvulsant, anti-inflammatory and antiviral recyclability of the catalyst and high yields of the product agents and HIV protease inhibitors. A mild and efficient which makes it useful and attractive process for the procedure has been developed for the monosulfonylation synthesis of β-aminoalcohols. [Catalysis of various amines using mesyl or tosyl chlorides in communications 2007, 8, 1876] water at room temperature to afford the corresponding sulfonamides in high yields. [Tetrahedron Lett. 2008, 49, 348]

• Selective reduction of aromatic azides to amines

• Synthesis of β-hydroxysulfides β-Hydroxysulfides are important building blocks for the A selective and facile method for the reduction of synthesis of higher functionalized organic molecules. A aromatic azides to amines by employing boron trifluoride highly efficient and environmentally benign method has diethyl etherate and sodium iodide has been developed. been developed for the direct one-pot synthesis of β- This methodology has been applied towards the hydroxysulfides in good yields under mild and neutral preparation of biologically important imine containing conditions from alkenes and thiophenols in the presence

Biennial Report 2007-2009 31 Synthetic Organic Chemistry & Drug Intermediates

of aerial oxygen using a mixture of ionic liquid of the most frequently employed transformations in

[brim][BF4] and water. This protocol tolerates a wide organic synthesis. A simple and highly efficient method variety of functional groups or substrates and does not has been developed for the tetrahydropyranylation of require either acid or base catalyst. Ionic liquid can be alcohols by their reaction with 3,4-dihydro-2H-pyran recovered and reused for a number of runs with (DHP) using a catalytic amount (0.01-1 mol%) of negligible loss of activity. [J. Mol. Cat. A: Chemical aluminum triflate under solvent-free conditions. The effect 2007, 272, 26] of various factors like temperature, amount of the catalyst, and molar ratio of the substrates on the reaction conditions has also been studied. The added features of this method over earlier reported processes include its simplicity, clean reactions, high yields, shorter • Synthesis of tetrahydroquinolines reaction times, absence of organic solvents, and large The tetrahydroquinolines moiety is an important scale practical synthesis. [Can. J. Chem. 2008, 86, structural component of a number of natural products. 1099] The reaction of arylazides with 2,3-dihydro-2H-furan and 3,4-dihydro-2H-pyran in the presence of chlorotrimethylsilane-sodium iodide (TMSCl-NaI) affords the corresponding 1,2,3,4-tetrahydroquinoline derivatives in an efficient manner and most of the compounds exhibited cis selectivity. The aza-Diels-Alder reaction APPLIED RESEARCH may proceed through in situ generation of aryl amines • followed by the reaction between 2-azadiene and another Development of process know how for Eptifibatide equivalent of cyclic enol resulting in the formation of (Sponsored by Biocon Ltd) 1,2,3,4-tetrahydroquinolines. This approach is carried A new process route has been developed for preparation out under extremely mild and neutral conditions and of Eptifibatide drug in lab scale (25 gm batch) and has provided a novel as well as efficient synthesis of details experimental procedures have been provided to tetrahydroquinoline derivatives. The reagent employed sponsor. for this process is rather inexpensive, non-stinking and non-toxic; hence this is a practical protocol. [J. Mol. Cat. A: Chemical 2007, 274, 133] • Synthesis of 3,4-dihydropyrimidin-2(1H)-ones Dihydropyrimidinones are known to have properties such as antibacterial, antiviral antitumor and antihypertensive agents. In pursuit of developing a solventñfree methodology for the preparation of these biologically important compounds, a mild and efficient synthesis of

dihydropyrimidinones using Cu(BF4)2 XH2O (5 mol%) as a catalyst under solvent-free conditions has been • Non-natural peptides in asymmetric catalysis: metal developed. This protocol has several advantages such mediated synthesis of peptide based materials as a mild solvent-free conditions in short reaction time, and their applications (Indo-French Collaboration excellent yields and simple experimental product Project) isolation procedures that makes this process useful The main objective of the project is to undertake the and attractive protocol (Biginelli) for the preparation of studies on peptide-metal asymmetric catalysis and dihydroprimidinones. [Catalysis Communication 2007, establish newer and novel protocols in asymmetric 8, 1929] synthetic reactions. In this direction, new metal catalysts and novel amino acids for their conversion into new peptides and chiral peptide-metal catalysts, will be designed and synthesized. IICT team prepared b-peptide derivatives with unsaturated • Tetrahydropyranylation of alcohols side chains, and sent them to France for further catalytic Protection of hydroxyl groups by their conversion to transformations. Cyclic tri and tetra b peptides have the corresponding tetrahydropyranyl (THD) ethers is one been synthesized with the objective of coordination to

32 Biennial Report 2007-2009 Synthetic Organic Chemistry & Drug Intermediates

metal centres. In France, the first activity was dedicated synthesis of Fondaparinux (pentamer) and study of their to the allylation of free amino acids to obtain N,N anti-thrombotic properties. IICT has already prepared diallylated and N,N,O triallylated amino acid derivatives. 25 LMWHís and supplied to BBIL for testing their anti- Development of ruthenium-based catalytic systems able thrombotic properties. Presently, all the monomers and to perform selective allylation of the amino and carboxylic the required dimers have been prepared which will be groups of free amino acids were developed. This further coupled to obtain the target molecule, catalytic reaction will be tested to introduce allylic group Fondaparinux. into peptide structures, when the classical procedures • ìNational Facility for Combinatorial Natural fail. The work also was initiated on the amino acids Productsî (Sponsored by DST, and CSIR, New and peptides submitted by IICT team. Preliminary results Delhi. are available. • The objectives of the project is to create state of the • Design and synthesis of C-2 symmetric proline art research group in chemistry of natural products and derivatives for asymmetric organic reactions combinatorial chemistry with a target to synthesize New strategies have been developed for the synthesis atleast 1,00,000 compounds. Also includes installation of C-2 symmetric diamine, using D-mannitol as a chiral of mol bank facility wherein compounds synthesized pool material. With this diamine synthesized few phase across the country are pooled up by offering incentives transfer catalysts for asymmetric organic and this storage facility will be available for at least one transformations. million compounds. • Providing Synthetic chemistry services in order to supply building blocks (Sponsored by EVOLVA Biotech Pvt. Ltd., Switzerland) The objectives of the project are to synthesize the given targets for Evolva, which will be screened for various cell lines to find their biological activity focusing • Design and synthesis of C-2 symmetric chiral phase on anti-viral, anti-fungal, histone-deacetylaze inhibition transfer catalysts for asymmetric organic reactions. (HDAC) etc. Till date IICT has synthesized various Synthesized C-2 symmetric chiral tertiary amine and classes of compounds and provided to Evolva. Among using this synthesized new class of enamine and phase these compounds, one compound (EV-077-3201) transfer catalysts. showed potent anti-fungal activity, for which IICT has provided excellent process procedures. Using this process Evolva is able to make this compound in kilogram scale and this compound has recently successfully completed Phase-I clinical trials. • Sustainable Chemistry R&D (INDO-FRENCH Project): A laboratory is set up in IICT for doing sustainable • chemistry with the support of CNRS, France and CSIR, ìNew generation of low molecular weight Heparin India. The objectives of this joint project are to share analogues as anti- thrombotic agents and their the knowledge between Indian and French scientists to pre-clinical evaluationî (Sponsored by DST, New do collaborative projects for sustainable chemistry. The Delhi and Bharat Biotech International Pvt. Ltd., main projects included under this umberella are NCEís Hyderabad). for cancer treatment and CNS disorders besides process The objectives of the project are synthesis of low- development for pharmaceuticals and materials involving molecular weight heparin (LMWHís) analogues and total green chemistry principles.

Biennial Report 2007-2009 33 Agrochemicals

APPLIED RESEARCH BASIC RESEARCH • Development of Novel Fungicides (NMITLI • Transformations with (Bromodimethyl)sulfonium programme) : Development of new protocols for This project was undertaken under NMITLI programme synthesis of bioactive molecules and intermediates jointly with Rallis India Ltd., Main objective of the with special stress on performing reactions under programme is to synthesize NCEís (by IICT) and screen solvent-free conditions led to the exploitation of them (by Rallis) for their fungicidal activity. New versatile catalyst, (bromodimethyl) sulfonium heterocyclic compounds were synthesized and bromide, for the following transformations screened for fungicidal activity against Pyricularia 1. (Bromodimethyl)sulfonium bromide mediated Michael oryzae, Rhizoctonia solani,Drechslera oryzae, Fusarium addition of thiols to α, β-unsaturated ketones: J. oxysporum .f. sp. cubense, Pythium aphanidermatum. Sulfur Chem., 2007 Ten NCEs with moderate to excellent activity were identified and are under field trials by M/s Rallies India Ltd. • Report Preparation A report entitled ìComprehensive studies on the application of stilbene derivativesî with special reference to 4,4í-diaminostilbene 2-2 ë-disulphonoic acid was prepared and submitted to M/s. Deepak Nitrite Ltd., 2. Three component one pot synthesis of β-amino Pune. ketones mediated by • Development of Novel Insecticidal & Fungicidal Compounds (Sponsored by ISAGRO, Italy) Main objective of the project is to synthesize NCEís for pesticidal activity and supply to sponsorer for its evaluation. New heterocylic compounds were synthesized and sent for testing for their Insecticidal / Fungicidal activity to M/s ISAGRO bromodimethylsulfonium bromide (Ind. J. Chem. B. Ricerca Italy. 20 compounds were synthesized by IICT 2009). and they are under evaluation by ISAGRO. Evaluation results are awaited. • Synthesis and antimicrobial activity of novel C- • Design and synthesis of new chemical entities linked imidazol glycoconjugates with new mode of action (ryanodyne / antagonist) (Supra Institutional Project) Novel C-linked derivatives have been The main objective of the project is to synthesize NCEís synthesized in good to excellent yields and to overcome the resistance problem plagued with characterized by analytical and spectral analysis. Four current insecticides dominated by AChE inhibitors. of the newly synthesized compounds exhibited moderate antibacterial activity. (Bio. Org. Med. Chem. • Process for the isolation of karanjin from Pongamia Lett., 2008, 18, 1167-1171). pinnata (karanja) seeds Commercially viable process has been developed for the isolation of karanjin (biologically active) having purity up to 95 % from karanja seeds by simple solvent extraction and fractionation techniques. Process is ready for release.

34 Biennial Report 2007-2009 Agrochemicals

polyhydroxyalkyl- and C-glycosylfurans from unprotected sugar aldoses An efficient method for the synthesis of Garcia Gonzalez polyhydroxyalkyl- and C-glycosylfurans from unprotected sugar aldoses with β-keto esters by Knoevenagel condensation in the presence of anhydrous

FeCl3 in excellent yields (Synthesis, 2009, 2278-2282).

• Synthesis of Novel Analogues of (+)-Varitriol via • A highly efficient regioselective synthesis of Oleffin Cross-Metathesis Reaction substituted pyridine and tetrahydroquinolinones. Novel analogues of (+)-varitriol have been synthesized Pyridine ring system is a central unit in several natural via olefin cross-metathesis reaction using Grubbís and synthetic molecules of therapeutic, pharmaceutical catalyst. Newly synthesized compounds were screened and agrochemical importance. Accordingly a series of for cytotoxicity and they showed mild activity against RAW264.7 and HT29 cell lines. new pyridine and tetrahydroquinolinone derivatives were synthesised with variable substitutions using enaminones as starting materials. [Tetrahedron 2007, 63, 13024; Synthesis 2007, 187]. Work is in progress to further functionalize these compounds to screen for agrochemical use.

• Design, synthesis†and evaluation of new calix- pyrroles for molecular and ionic recognition. All the compounds showed mild activity and compounds Design and synthesis of calix-pyrrole based synthetic 4a and 4b displayed more activity among the screened anion receptors is the subject of current interest due to compounds. Though the compounds showed mild their potential applications in areas as nuclear waste activity, the synthesis and screening of more analogues remediation, environmental chemistry and biology. of varitriol, both protected unprotected, would give scope for further work in this area. (Bio. Org. Med. Chem. Several simple calix[4]pyrroles have been synthesized Lett., 2008, 18, 2351-2354). and examined by mass spectral differentiation of cone, partial cone, 1,3-alternative conformations using their • FeCl3 in ethanol/water: Highly efficient catalytic fragmentation pattern. [J. Mass spectrometry, 2007, system for the synthesis of Garcia Gonzalez 42,1194]. Further work on the synthesis and evaluation

Biennial Report 2007-2009 35 Agrochemicals

of new calix-pyrroles and their molecular and ionic • Chemical Examination of Pouzolzia indicia recognition in solution and gas phase is in progress. (Urticaceae) The extract from the stem and leaf powder of Pouzolzi indica was fractionated by chromatography. The fractions were tested for mosquito larvicidal activity. Some of these fractions containing sterol and other unidentified minor constituents were found to be active. The formulated (EC) crude extract was found to exhibit larvicidal activity. DEVELOPMENT OF NOVEL & ANALYTICAL METHODS • Quantification of Biopesticide Active Ingredients A simple and reproducible analytical HPLC method has been developed to adopt as a standard operating • Chemical Examination of Pygmacopremna analytical procedure for the quantification of Azadirachtin, herbacea ( Gantubharangi ) Squamocin and karanjin, the active principles present Two ìNew novel diterpenoids (1and 2) were isolated in the biopesticide formulations of Neem, Custard apple from roots of indigenous medicinal plant and karanja respectively. The facility of quantification of Pygmacopremna herbaceaî The structures of these active ingredient of different biopesticide formulations compounds were characterized by spectral methods has been extended to various Government and Private particularly 1D and 2D NMR Organizations • Analytical Method to Identify Impurities in APIís Optical rotations of samples received from IICT and industries were recorded on Polarimeter. Fluorescence spectrometer was used to identify impurities in a given Active Pharma Ingredient (API) ñ several samples were analyzed for local industries. Photochemical equipment was utilized to develop laboratory process for organic photochemical reactions.

36 Biennial Report 2007-2009 Pheromone Chemicals

Insect pheromones provide environmentally safe pest management by manipulating the behaviour of insects. Pheromone application in pest management is mainly associated with species specificity, safety to non-target organisms, ease of use and efficacy in reducing the damage. In India, after certain initial constraints the potential of insect pheromones as a tool for the quality food production is gradually gaining the attention of farming ❖ community. The Pheromone Group at IICT is leading the All the identified compounds were successfully way in the development (isolation, identification, synthesis synthesized in the laboratory at a 500mg to 1gm batch of pheromone components and dispenser development) size. and implementation (field evaluations and demonstrations ❖ Confirmed the bio activity of the synthesized possible of developed pheromone indigenous dispensers) of pheromone compounds in the† laboratory† both by EAG pheromone application technology (PAT) for the and GC-EAD management of important pests of various field crops. Isolation and identification of pheromone systems of BASIC RESEARCH groundnut bruchid Caryedon serratus and cardamom capsule borer Conogethes punctiferalis are under active Isolation and Identification of Pheromone Components progress. ❖ Confirmed the existence of female based pheromone system in two pomegranate fruit pests Eudocima APPLIED RESEARCH materna and Deudorix isocrates and successfully • Synthesis and dispenser development identified seven components from their pheromone gland ❖ extracts utilizing the unique techniques Successfully synthesized all the pheromone Electroantennogram (EAG), EAG coupled gas components of cotton bollworms Helicoverpa armigera, chromatography (GC-EAD), GC coupled mass Earias vitella and Pectinophora gossypiella at 50 gm spectrometry (GC-MS), windtunnel etc. batch size in the laboratory by developing feasible preparative methodologies. The list of possible pheromone components isolated and identified from female Eudocima materna pheromone blend are as followed

1. Z3- Hexenylacetate, 3. Z 11 - Hexadecenal††† †††† ††

2. E 9- Tetradecenal, † 4. Z 13-Octadecenal

❖ Developed an effective sex pheromone based package tool along with the methodology of implementation for Possible pheromone components isolated and identified the control of the three cotton bollworms. The developed from female D.isocrates package is very much useful and viable for the farming community for the management of cotton bollworms 1.† 5- Hexene-1ol,††††† †††††††††††† and to produce high quality cotton through IPM.

2.† E 9-Tetradecenol,††††† ❖ The preparative methodologies for the synthesis of 3.† E - Hexadecenol†††††† 11 pheromone blends of cotton bollworms are ready for

Biennial Report 2007-2009 37 Pheromone Chemicals

transfer to entrepreneurs.† Submitted as a project report and Rural Development Trust (RDT) at Ananthapur helped to DBT, New Delhi. in conducting the field trials. ❖ Monitoring and mass trapping techniques were employed to control groundnut leaf miner (GLM) infestation while implementing PAT.

❖ Benefits of PAT are† brought to the knowledge of resource poor farmers in farmersí field days and workshops organized by Agricultural Research Station (ARS) of ANGRAU at† Ananthapur,† Agribiotech (APNL/BTU ❖ Successfully achieved the sex pheromone blend programme) at Palem† and College of Agriculture at synthesis of groundnut leaf miner (GLM) in the Dhule (Maharashtra) through display of† posters and laboratory to conduct large scale filed demonstrations delivering lectures in local languages. in order to check its viability by controlling GLM menace through implementation of Pheromone Application ❖ Groundnut growing farmers belonging to different villages Technology (PAT) in Ananthapur district and extension workers of Agricultural research station (ARS) ANGRAU and Rural ❖ Demonstrated and transferred preparative methodologies Development Trust (RDT) at Ananthapur are given for the pheromone components of groundnut leaf miner training in PAT in the fields. to Balaji Agro chemicals, Hyderabad.† ❖ Assisted the commissioner of Agriculture of A.P. in ❖ Demonstrated and transferred preparative methodologies analyzing the various pheromone lures for their for the pheromone components of Sugarcane Internode genuineness. Accordingly the reports were submitted borer and Early shoot borer to Rajashree Sugars Pvt. for the proper utilization of PAT.† Ltd. Coimbatore. National & International Collaborations ❖ Synthesized four probable pheromone components of uzi fly at 2 gm batch size and provided to State Pheromone group has established several collaborative Sericulture Research and Development Institute KSSRDI linkages with national & international agricultural bodies, Bangalore. research institutes and universities. Two DBT funded projects one in collaboration with G.B.Pant University of Field Evaluation and Popularization Agriculture & Technology, Pantnagar and the other with Pheromone application technology is identified under National Research Center for Sorghum (NRCS), Hyderabad Agrochemicals as one of the thrust area in CSIR XI research are in progress. One ICAR special grant project with Plan proposal. Tamilnadu Agricultural University and a DST sponsored Indo-Argentine collaborative project are also under progress. ❖ Successfully demonstrated PAT with IICT synthesized pheromone blend in the 100 hectares of groundnut fields The achievements of Pheromone Group and the available of Ananthapur district, the major groundnut growing expertise there in have made IICT to get invited to join as district of A.P.† for the first time both in Rabi and Kharif one of the working partners in a consortium of six countries seasons. Agricultural research station (ARS) ANGRAU to submit a joint project proposal entitled ìEuropean Project

38 Biennial Report 2007-2009 Pheromone Chemicals on Invasive Insect Surveillanceî to European Commission PAT. The various benefits that are envisaged through rural (EC). pheromone lures making center are as follows. DST sponsors exchange of visits under Indo-Argentine ❖ Chances for spreading the spurious chemicals will collaborative project programme ìInsect pheromones and be reduced. kairomonesî. The main objectives of the project are ❖ Farmers become self-sustainable in employing the technology. ❖ Isolation, identification and synthesis of†† pheromone system of Castor capsule borer Conogethes punctiferalis ❖ Pheromone lures will be made available to the farmers (Lepidoptera: Pyralidae) at lower cost. ❖ Generation of job work for the qualified people at the ❖ Synthesis of pheromone components of Cabinet and village level. Warehouse beetle - Trogoderma granarium (Coleoptera: Dermestidae). ❖ Sustainability for the production of pesticide free produces. ❖ Development of suitable dispenser technology for the identified and synthesized†† Pheromones

Unique/Major Facility set up Established rural pheromone lures making center in Mahaboobnagar district, Andhra Pradesh. Pheromone lures making center is established mainly for the benefit of the small farm holders and on the whole the society. Extension workers of SDDPA, Wanaparthy, were trained by IICT Pheromone group in all the aspects necessary for the functioning and maintenance of the rural pheromone lure- The farmers in and around villages can procure the required making center. Pheromone lures making centers enable commercial /technical grade pheromone blends from the farmers to procure genuine or required pheromones lures national and international market and prepare the lures by themselves at affordable rates. Involvement or with the established facilities at the center. In this way participation of farmers help them to gain confidence in they will be saving at least 50% on the market price.

Biennial Report 2007-2009 39 Fluoroorganics

BASIC RESEARCH Organic molecules with fluorine or trifluoromethyl group at an appropriate position promotes oxidative thermal stability, permeability, binding affinity and transport mechanism due to improved lipophilicity. Recent statistics indicates that, out of top ten drugs sold in market, five drugs containing fluorine or trifluoromethyl group. Therefore, the current trend is driving more towards synthesis of fluorinated molecules of biological interest. Thus, we have synthesized several novel fluorinated molecules such as, hexafluoropropanols, pyridine derivatives and TEMPO based fluorous catalyst reactions are screened for anti-bacterial, anti-cancer and anti-diabetic activity. The promising compounds have been identified. • β-acetamido carbonyl compounds

M. Sridhar et al., Tetrahedron Lett., (2009), 50, 3897-3900

• Pyridine derivatives

78 ñ 87% A novel method for preparation of poly-substituted pyridines under Lewis acid catalysis has been Ravindra M. Kumbhare et al., Bioorganic & Medicinal developed. Chemistry Letters 18 (2008) 4130ñ4132 • Arylidene malanonitriles

Though MgF2 does not contain any Lewis acidic sites on its surface, this solid catalyst was found to be highly efficient in catalyzing Knoevenagel condensation of variety of arylaldehydes with malanonitrile producing substituted olefins with exclusive E-selectivity in high yields. APPLIED RESEARCH Fluoroorganic Division is working with Indian industrial clients in process development to meet their requirement. • Hydrofluoroethers R.M. Kumbhare and M. Sridhar, Catalysis Commun., Fluoroorganic division provided consultancy services to M/s. Nicholas Pyramal India Ltd., Mumbai for the (2008), 9, 403 preparation of , a hydrofluoroether used as • Hexafluoropropanols anaesthetic with a contract value of 30 lakh. As part of continued interest in development of

hexafluoroisopropanol functionalized siloxane polymers, HF we wanted to prepare hexafluoroisopropanol CF3CHClOCH3 CF3CHFOCH3 functionalized alkenes through carbonyl-ene reaction with hexafluoroacetone. Commercially, • Synthesis of Siloxane Fluoro Alcohol (SXFA) hexafluoroacetone is available in trihydrate form, which (Poly(oxy{methyl[4-hydroxy-4,4-bis(trifluoromethyl)but-1- is inert to carbonyl-ene reaction with alkenes. To en-1-yl] silylene}), which was popular by the trivial name overcome this problem, we have developed a novel ëSXFAí is a functional polymer containing method for activation of hexafluoroacetone trihydrate hexafluoroisopropanol groups. This acidic hydrogen bond using molecular sieves as catalysts, which gave efficient donor polymer is useful, when used in the form of a carbonyl-ene reaction with a variety of alkenes. thin film in micro cantilever sensors, for detection of

40 Biennial Report 2007-2009 Fluoroorganics

noxious chemicals such as explosives in very low of flow control valves operated with electronic signal concentrations (ppb). This polymer is not available remotely operated and integrated with electronic weigh indigenously and a process route was developed scale via flow indicator with auto / manual facility. The successfully for SXFA and the material was submitted reactor exit stream is connected to a product cooler to High energy materials research laboratory, Pune and which is suitably designed for normal flow rates with Indira Gandhi Center for Atomic Energy (IGCAR), water / coolant circulation. The product stream is Kalpakam for their requirement in development of connected to a scrubber mounted on a 20 lit. capacity cantilever sensors. holding tank (with level guage) and provided with alkali re-circulation pump. Gas entry from the bottom of the scrubber column with top exit and counter current alkali liquid circulation. The column is filled with polypropylene packing of suitable size. The dryer is a cylindrical vessel of one lit. holding capacity filled with molecular sieves / silica gel. The organic product is condensed and collected in glass receivers under cryogenic conditions using liquid nitrogen as medium. The control panel with UPS integrated with skid • Development of process for Acetohydroxamic Acid mounted system. All the inter- connecting lines should (AHA) be of swagelok make SS tubes, fittings, ferrules, nuts, The alkali metal salts of acetohydroxamic acid are valves etc. excellent chelators for heavy metals such as copper, iron, cobalt, nickel, chromium, manganese, vanadium, uranium, gold, platinum, palladium and rhodium. Thus, it is a valuable chemical for extraction of plutonium and uranium in pure form from the spent fuel of the nuclear reactors. Presently IGCAR is importing this chemical at a price of Rs.1.2 lakh/Kg. An economically viable method for preparation of AHA has been successfully developed and the process was demonstrated to IGCAR, Kalpkam at 100 g/batch. AHA has also importance in medicinal chemistry for curing urinary tract infections and reducing stone formation. • New facilities created : Pyrolyser reactor system commissioned The MOC of the reaction is a seamless tubular Incolloy- 800H, 3/8" NB pipe of 80 schedule and with a three zone heating provision by segmental electrical furnaces. The temperature of the reactor is maintained by programmable (PID) controllers with solid State Power controllers and manual back pressure regulator is fixed to read the reaction pressure. Feed section contain gas lines or liquid lines of MOC SS-316 with a provision Pyrolyser

Biennial Report 2007-2009 41 Inorganic & Physical Chemistry

APPLIED RESEARCH We have redesigned and introduced extended-p • conjugation concept along with ëpush-pullí concept in • Synthesis of new dye molecules for Dye Sensitized order to increase e of phthalocyanine macrocycle. The Solar cells (DSSC) applications (IICT-Aisin Cosmos new sensitizers are shown below. R&D Co. Ltd., Japan collaborative project) The developments of clean renewable energy sources are of vital importance as fossil fuel resources are depleting rapidly. In this regard, dye-sensitized solar cells are a cleaner and low cost alternative technology to existing conventional solid-state photovoltaic devices. In these cells, the sensitizer is one of the key components for high power conversion efficiencies. The most successful charge-transfer sensitizers employed All these new sensitizers are shown very good so far in such cells are ruthenium polypyridyl performance in test cell device. These are very cheap complexes, produced solar-energy-to-electricity sensitizers compared to existing ruthenium polypyridyl conversion efficiencies (η) up to 11%. In spite of this, complexes. the main drawbacks of these sensitizers are the lack of absorption in the red region of the visible spectrum • An ecofriendly process for paracetamol : and also relatively low molar extinction coefficient above Conversion of nitrobenzene to para -aminophenol 600 nm. With respect to availability and stability point and Conversion of p-aminophenol to paracetamol of view phthalocyanines are excellent sensitizers, which Sponsored by (IFCPAR). have been an active focus of intense research for the Single step preparation of p-aminophenol is carried from development of efficient light-to-energy conversion nitrobenzene using platinum on carbon and solid acid devices. Moreover, phthalocyanine molecules have unique catalysts in a 100ml autoclave. Large-scale experiments properties in terms of light absorption in the far visible were optimized in a 700ml autoclave. A European patent region of the solar spectrum (Î = 690 nm) with molecular has been filed. extinction coefficients (Â) higher than 100,000 dm3 Mñ • 1 cmñ1 and good chemical stability. • Recovery of Nickel as Pure Nickel Carbonate from Spent Raney Nickel Catalyst Sponsored by (Cadila But, phthalocyanine applications to DSC was limited Pharmaceticals, Bhat, Ahmedabad) due to lack of solubility and planarity nature of Developed a cost effective process and demonstrate macrocycle. For this reason, we have designed and the technology on bench scale (100 gm batch spent synthesized an unsymmetrical phthalocyanine based catalyst processing) to recover nickel as pure nickel on ëpush-pullí concept. It has three bulky tert-butyl carbonate from spent Raney nickel catalyst. The unit groups which act as both electron releasing and operations involved are washing the spent catalyst with increase the solubility of macrocycle in common organic water to remove soluble impurities, leaching with dilute solvents and two carboxyl groups act as electron sulphuric acid to leach out >95% nickel with minimum withdrawing nature and also serves to anchored the contamination of aluminum, purification of leach liquor nanocrystalline TiO (PCH001). This shows an efficiency 2 for alumina removal by alkali precipitation and finally of 3.05% in liquid and 1% with solid redox electrolytes. recovering the nickel as pure nickel carbonate with a This is the major break through in phthalocyanine based purity of >99.9%. Finally complete flow sheet of the DSC test cell device. We have extended the concept process with material balance is demonstrated to the and reported PCH003, which has alkoxy groups in place party. Based on IICT know-how, client has put 500kg/ alkyl groups. PCH003 also shows excellent performance day nickel carbonate production plant at the factory in DSC test cell device. site. • Process development of some important chiral pharma intermediates via asymmetric hydrogenation technologies (DST-IICT-Unimark Collaborative project). Synthesized chiral BzO-BIPHEP type atropisomeric ligands . These chiral ligands are complexed with Ru and Rh and used for asymmetric hydrogenation

42 Biennial Report 2007-2009 Inorganic & Physical Chemistry

reactions. The work envisioned herein involves the stabilized on nanocrystalline magnesium oxide with ionic development of asymmetric hydrogenation technology liquids has been developed. of select prochiral substrates of industrial importance and to benchmark the data with commercial catalysts. • Development of catalytic processes for making intermediates of sandalwood and other fragrance chemicals Sponsored by (Givaudan Schweiz AG, Switzerland). Oxidations New process development of intermediates for Selective oxidation of various alcohols using molecular sandalwood and other fragrance chemicals has been oxygen. initiated using supported/unsupported catalysts. Under Ruthenium species stabilized on NAP-MgO by the this program several supported acid and base catalysts incorporation of choline hydroxide, a basic ionic liquid for were developed and applied for the organic molecules the selective oxidation of alcohols at atmospheric pressure interested to the client. Key product samples have been in the presence of molecular oxygen is developed. handed over to the sponsored party.

BASIC RESEARCH • Nanomaterials Nanocrystalline metal oxides find excellent applications Efficient oxidation of primary and secondary alcohols to as active adsorbents for gases and destruction of the corresponding carbonyl compounds using molybdenum hazardous chemicals and catalysts for various organic acetylacetonate stabilized on nanocrystalline magnesium transformations. These high reactivities are due to high oxide (aerogel-prepared MgO, NAP-MgO) with defined surface areas combined with unusually reactive shape and size in the presence of molecular oxygen in morphologies. These highy acive nanomaterials have excellent yields is described. been successfully applied for various organic transformations. Some of them are described below. Reductions Reduction of a variety of aromatic and aliphatic nitro compounds to the corresponding amines at ambient temperatures in good to excellent yields was developed • Apatite supported metal catalysts using nanocrystalline magnesium oxide stabilized palladium(0) catalyst in the presence of molecular Apatites are metal basic phosphates for which the is M (PO ) (OH) [M = divalent metal] hydrogen as the reductant (Scheme 1). 10 4 6 2 and the most typical apatite is calcium hydroxyapatite

Ca10(PO4)6(OH)2 (CaHAP). CaHAP attracted wide attention due to its versatile applications in the field of bioceramics, chromatographic adsorbents and acid base catalysis. Fluorapatites (FAP) are metal basic phosphates for which the chemical formula is This catalyst was further exploited for sequential Heck M (PO ) (F) (CaFAP) [M = divalent metal]. coupling reaction of haloarenes (chloro, bromo and iodo) 10 4 6 2 and styrenes followed by hydrogenation of the resulting Conjugate addition of organoboron reagents to a,b- stilbenes by employing molecular hydrogen under unsaturated carbonyl compounds to yield conjugate atmospheric pressure (Scheme 2) addition products by using rhodium fluorapatite catalyst is developed.

The transfer hydrogenation of various carbonyl compounds (Scheme 3) using ruthenium nanoparticles

Biennial Report 2007-2009 43 Inorganic & Physical Chemistry

• Hydrotalcite supported metal catalysts yields was easily achieved by the catalytic amount of

A catalyst system consisting of copper-aluminium KI or I2 in combination with TBHP as the external hydrotalcite-chiral diphosphine ligand for asymmetric oxidant. This non transition metal catalyst is cost hydrosilylation of several ketones, using effective and provides easy workup and separation of polymethylhydrosiloxane (PMHS) as the stoichiometric the product. reducing agent at room temperature, with moderate-to- • Polymer nanocomposites as electrochromic excellent enantioselectivities is developed.The catalyst materials is recovered by simple centrifugation, and the efficiency Macromolecules featuring alternating conjugated of the catalyst remains almost unaltered even after aromatic segments and heteroatoms are of interest for several cycle. many current and future applications. A convenient olefin metathesis synthesis of homologous silicon and siloxane containing chain and ring architectures featuring alternating aromat and heteroatom containing segments have been done. Further macro cycle containing two trans stilbene units that are connected by two germoxane linkages, connecting the Ge atoms to the aromatic segments has also been done. Conjugate addition of organoboron reagents to a,b- • Conducting polymer fibers and nanocomposites of unsaturated carbonyl compounds to yield conjugate high Electrical Conductivity as Solid Polymer addition products by using rhodium fluorapatite catalyst Electrolyte (SPE) is developed. Polymer nano fibers of homo and copolymers using aniline, pyrrole monomers have been synthesized. Polymer nanocomposites are synthesized by using above mentioned polymers and nanoparticle fillers like

montmorillonite clay,TiO2, SnO2, etc. These new organic conducting polymers and polymer nanocomposites may be suitable as SPE for solar cell, rechargeable battery • Oxidative transformations of organic functional application. groups by iodine/iodide reagents • Biopolymer/ Biodegradable Polymer (a) Oxidative Amidation of Aldehydes and Alcohols with Nanocomposites multifunctional materials (DBT) Primary Amines Catalyzed by KI-TBHP : Oxidative The main objective of the present project is directed amidation of aldehydes and alcohols with amines to towards the synthesis and characterization of bio- give the corresponding amide products in excellent nanocomposite materials and their further application yields and >98% ee is achieved by the catalytic amount in biotechnology, mainly focusing food packaging of KI in combination with TBHP as the external oxidant. materials. This method avoids the use of expensive and/or air- • sensitive reagents. Preparation and photophysics of HPTS-based nanoparticle-assembled microcapsules (b) Selective Oxidation of Aromatic Amines to Nitro A methodology was developed to encapsulate hydroxy derivatives using Potassium Iodide - tert-butyl pyrene trisulfonate (HPTS) inside silica microcapsules hydroperoxide Catalytic System:Direct oxidation of and carry out spectroscopic and fluorescence lifetime aromatic primary amines to the corresponding nitro studies of these encapsulated HPTS. The spectroscopic compounds selectively in 47-98% yields has been evaluation of encapsulated HPTS showed completely achieved by using potassium iodide as catalyst and different but more-stable optical properties by lowering tert-butyl hydroperoxide as the external oxidant. The the energy gap between the excited and ground state. present catalytic system works well for both electron Based on a solvatochromic study, a higher polarizability rich and electron poor substrates. was recorded inside the microcapsule. Temporal (c) Catalytic oxidative conversion of alcohols, aldehydes evolution under continuous irradiation indicates that the probe present inside the silica microcapsule is highly and amines into nitriles using KI/I2-TBHP system: Oxidative conversion of alcohols, aldehydes and amines photostable compared to pyrene in solution, suggesting to give the corresponding nitrile products in excellent that the microcapsule can provide extra photochemical

44 Biennial Report 2007-2009 Inorganic & Physical Chemistry

stability to not only the probe molecule during molecular polypeptides and polyamines directly catalyse ZnO sensing, but also the guest (drug) molecule while mineralization under ìgreenî conditions of room applied as drug delivery system. temperature and neutral pH. The polyamines not only act as mineralizing agents for the formation of ZnO • Synthesis of monodispersed magnetic nanoparticles, but also self-assemble the nanoparticles nanoparticles to form spindle-like morphologies at these very ambient Efforts are on to obtain well dispersed nanoparticles conditions. Both the directional growth of ZnO and its magnetic particles in water by surface functionalization luminescent property have a pH dependency. At higher of the magnetic nanoparticles. The synthesis of capped pH, the ZnO shape changes to a rodlike morphology semiconducting oxide nanoparticles is accomplished, that exhibits green photoluminescence with different where it is established that aromatic 1,2-dihydroxy intensity than that for ZnO spindles. compounds have a strong tendency to bind onto the • surface of inorganic nanoparticles. The presence of long • Syndiotactic polystyrene with Half Titanocene/MAO aliphatic chain on the surface of the ferrite nanoparticles Catalyst makes them highly dispersible in non-polar organic Styrene polymerization was carried out by simple half- solvents like chloroform, hexane etc. for more than six titanocene complex [cyclopentadienyl titanium

months. trichloride] (CpTiCl3) and pentamethyl [cyclopentadienyl titanium trichloride] (Cp*TiCl ) combined with • Monolayer-protected colloidal nanoparticles 3 methylaluminoxane (MAO) as a cocatalyst. The effects Monolayer-protected colloidal nanoparticles provide a of addition of 2,6-diisopropyl phenol on the catalytic versatile scaffold for protein surface recognition due to activity of the above catalytic systems and the their size, the ability to tailor monolayer surfaces with microstructure of the resulting polymer were a wide range of functionalities, and the templatability of investigated. DSC and 13C NMR results indicated the the surface monolayer. Furthermore, the wide range of formation of syndiotactic polystyrene in absence of core materials available, enhance the utility of these phenol and in low concentration of phenol. particles. TiO nanoparticles, functionalized with blue 2 • dextran, can be used as affinity chromatographic Polyaniline-SnCl2 (PANI-Sn). A highly efficient and columns. reusable catalyst for amide formation from acids and amines • Synthesis, Characterisation and Application of An efficient and reusable polyaniline supported Silica metal/metal oxide core shell nanoparticles stannous chloride (PANI-Sn) catalyst was developed Surface modification of nanostructures is a novel for the synthesis of amides in good to excellent yields technique to fabricate new and novel advanced from acids employing amines as amination agent. The materials. Strategies to attach various active functional amidation of acids over this heterogeneous catalyst organic, inorganic or biomolecules on the surface of was realized through the tuning of the reactions by nanostructures by another material to form core@shell simple exposure of the reactants to conventional heating structures has attracted the attention of many as well as ultrasound irradiation. researchers in recent years. An interesting extension • of the core@shell nanoparticles is the production of • Polyaniline Nanofiber as a novel matrix for enzyme hollow nanoparticles by removal of the core particles immobilization: case study with L-asparaginase and these hollow particles find applications in drug and Amylase delivery, or as reactors for specific recognition systems. In this study, L-Aspargenase and amylase enzymes Research was carried out on the ìSynthesis, were immobilized on polyaniline nano sized fiber Characterization and Application of Silica Core@Shell supports. L-Aspargenase and amylase are chosen as Nanoparticles for Various Organic Transformationsî. model protein enzymes for precise investigation about Reactions such as ring opening of epoxides with amines not only the immobilized state of enzymes but also its in water, conjugate addition of amines, diamines and functional activity on polyaniline nano fiber surfaces at thiols and selective oxidation of sulfides to sulfoxides different concentrations. are some of the reactions that have been carried out • Asymmetric Catalysis using the synthesized silica core-shell nanoparticles. • The easy-to-prepare dimeric bis(µ-iodo)bis((-)- • Bioinspired Morphology-Controlled Assembly of sparteine)dicopper(I) complex is used as a versatile ZnO Nanostructures catalyst for N-arylation of number of NH-heterocycles In a bioinspired methodology, positively charged with structurally divergent aryl halides including activated

Biennial Report 2007-2009 45 Inorganic & Physical Chemistry

aryl chloride substrates under mild conditions. The high conditions. This catalyst is reusable and offers high level Density Functional Theory (DFT) studies have been selectivity with good to excellent yields. carried out and they not only provide structural insights into square-pyramidal Cu(III) intermediate complexes derived from (-)-sparteine, but also highlight the important role of sterically demanding (-)-sparteine ligand framework in promoting activation of aryl-chlorine bonds for N-arylation of . • Heterogeneous catalysts for Biodiesel synthesis • Modified heteropoly acids as new generation Mg/La and Mg/Zr based mixed oxides are efficient catalysts for fine chemical synthesis catalysts for the room temperature transesterification of triglycerides of both edible and non-edible oils. The The role of vanadium and its location in Keggin ion of catalyst exhibited exceptional activity towards heteropoly molybdate was studied in detailed. The transesterification of oils within a short period of reaction specific location of vanadium in the 12- time and also showed good transesterification activity molybdophosphoric acid was found to affect the of oils even in presence of water and free fatty acids at catalytic redox performance. The catalyst with vanadium room temperature. present in the primary structure of the Keggin ion • possesses enhanced catalytic redox activity and Value addition to Bioglycerol: Catalysts for selectivity than when vanadium is present on the Keggin selective hydrogenolysis of glycerol. surface for both ammoxidation and oxidation reactions. Selective glycerol hydrogenolysis to 1,2-propanediol and ethylene glycol has been achieved over Ru/C in combination with solid acid as co-catalyst. The glycerol conversion and selectivity are related to the acidity of the catalysts, because there exists a linear relation between acidity and glycerol conversion.

Metal exchanged heteropoly acids: Hydroamination of alkynes with both aromatic and aliphatic amines Cu-ZnO catalysts with varying Cu to Zn weight ratio are proceeds efficiently in the presence of silver-exchanged highly active under relatively low H2 pressure for the tungstophosphoric acid (AgTPA) catalyst under solvent- glycerol conversion to propanediol. Different reaction free conditions to afford ketimines in excellent yields. parameters are studied and optimized the reaction conditions. • Novel nanosized ceria-based composite oxides for three-way catalytic (TWC) applications

Novel nano-sized CeO2-ZrO2 and CeO2-HfO2 combination solid solutions were prepared and characterized by Oxidation of various alcohols over heterogeneous iron various physicochemical techniques. The relative

and vanadium containing molybdophoshoric acid catalyst influence of SiO2, TiO2 and Al2O3 on the oxygen storage with molecular oxygen as oxidant afford the capacity was also systematically investigated. Further corresponding carbonyl compounds with excellent studies are under active progress to exploit these yields. catalysts for commercial applications. Two patents (USA) were also filed on this work in view of its commercial importance. Signed an agreement with an international company (NISSAN Co. Ltd, Japan) to exploit the developed materials for auto exhaust purification purposes. • Microwave induced combustion synthesis (MICS) Selective oxidation of primary and secondary allylic of nano-oxides alcohols were efficiently accomplished by using silver exchanged molybdovanado phosphoric acid catalyst with Nanocrystalline monophasic ceria-zirconia (1:1 molar molecular oxygen as oxidant under mild reaction ratio) solid solutions were synthesized by microwave

46 Biennial Report 2007-2009 Inorganic & Physical Chemistry

induced solution combustion synthesis method in a conversion/selectivity of furfuraldehyde to furfuryl alcohol. modified domestic microwave oven (operated at 2.45 In the case of cinnamaldehyde hydrogenation, the Cuñ

GHz frequency and 700 W power) in ~40 min from Co/SiO2 combination catalyst exhibited very promising

cerium nitrate and zirconium nitrate precursors using results, whereas CoñNi/SiO2 and NiñCu/SiO2 catalysts urea as ignition fuel. For the purpose of comparison, provided good yields of hydrocinnamaldehyde CeO -ZrO solid solutions were also synthesized by 2 2 • Cyclohexane oxidation coprecipitation method. The samples obtained by MISC method produced more active homogeneous SBA-15, a novel mesoporous material has been synthesized according to the templating route using monophasic Ce0.5Zr0.5O2, whereas coprecipitation method displayed compositional heterogeneity. P123 as a templating agent. This support either during • the preparation or after the preparation has been modified • Solid super acids for organic synthesis and by incorporation Au or Co or both. These catalysts transformations were tested at lab scale for cyclohexane oxidation at Sulfate, molybdate and tungstate promoted zirconia- 1MPa pressure and in the temperature range of 50 to based solid acid catalysts were synthesized by an 1600C in liquid phase conditions with either molecular unconventional method, which exhibited very strong oxygen or air. The catalyst yielded more than 15% acidity and interesting catalytic activity for the facile oxidation products (cyclohexanone + cyclohexanol). synthesis of diphenylureas, coumarins, 1,5- There is lot of scope for this process for scale-up studies benzodiazepines, and acylation of alcohols, phenols because the yields are far greater than the existing and amines, and protection of carbonyl compounds. A commercial process. Reusability of the catalyst tests 2- novel solid acid catalyst, SO4 /CeOx-ZrO1-x was also are to be done. formulated which can be effectively used for the • Adsorbents for the removal of H S, NH and alkali synthesis b-amino ketones and coumarins. Further work 2 3 metal ion vapor from coal gas is under active progress. Preparation of adsorbents for the removal of H S, NH • 2 3 • Catalysts for dehydration of alcohols and alkali metal from coal gas was initiated. These The dehydration of alcohols produces alkenes, which adsorbents will be tested by pressure swing adsorption are useful in polymer industries. The conversion of 4- (PSA) technology for removal of above mentioned methylpentan-2-ol to 4-methylpent-1-ene is an important pollutants in an online reactor at 20 atm and reaction. It has been observed from our studies that temperatures at and above 3500C. An online setup was

supported CeO2-ZrO2 and TiO2-based nanosized mixed fabricated for this purpose. oxides show excellent activity for the dehydration of 4- • Silver - Copper doped materials for water methylpentan-2-ol. Futher studies are under progress applications to exploit this catalyst for commercial utilization. • Ag-Cu catalysts supported on activated carbon with • Novel Catalyst for oxidative dehydrogenation (ODH) good microorganism controlling ability were synthesized. of ethylbenzene to styrene These catalysts are cost effective when compared to Efficient catalysts were designed based on supported Ag/C catalysts since major part of Ag is diluted with vanadium and cerium oxides, which catalyze the ODH Cu. of ethylbenzene to styrene at normal atmospheric • Combination of nitrobenzene hydrogenation and pressure utilizing CO2 as soft oxidant. The remarkable 1,4-butanediol dehydrogenation ability of this is that it prevents deactivation of dispersed Coupling dehydrogenation and hydrogenation reaction vanadium oxide leading to stable activity in the time- over a single catalyst eliminates of external hydrogen on-stream experiments and high selectivity to styrene source as in-situ generation of hydrogen from the at slight lower temperatures. dehydrogenation of reaction is utilized for the • Supported bimetallic catalyst for selective hydrogenation reaction. Cu based catalysts were hydrogenation of aldehydes successfully employed for the coupling of 1,4-butanediol High surface area silica supported transition metal- dehydrogenation and nitrobenzene hydrogenation. 1 • based bimetallic catalysts MñM /SiO2 (M = Co, Ni, and Catalytic Decomposition of Methane 1 Cu; M = Ni, Cu, and Co) were developed for selective Synthesis and characterization of Ni based catalysts hydrogenation of furfuraldehyde and cinnamaldehyde to for the CO free H production by catalytic decomposition their corresponding alcohols. The CuñCo/SiO and Niñ x 2 2 of CH4: Catalytic Decomposition of Methane (CDM) has Cu/SiO2 combination catalysts exhibited a high been found to be a better option to produce CO-free

Biennial Report 2007-2009 47 Inorganic & Physical Chemistry

hydrogen. This process, which operates at relatively widely reported centrosymmetric squaraines as high temperatures (673 K), involves the catalytic molecular materials decomposition of methane in a first step to produce b) Near Infra red (NIR) Dyes CO-free hydrogen and carbon nano fibers which are commercially useful compounds for several applications. Bis(benzofuranonyl)methanolate (BM4i4i) dye and For this purpose several supported mono and bimetallic croconate dyes (derivatives of oxyallyl molecules) in Ni catalysts have been synthesized, characterized and general are known to have intense transitions in the evaluated for the CDM process. Some of the results near-infrared (NIR) region, indicating small transition are published in reputed international journals. energies and large transition dipole moments. • Investigated using density functional theory/abinitio/ Steam Reforming of Bioethanol for the Production symmetry adapted cluster-configuration interaction of H for Fuel Cell applications 2 (SAC-CI) techniques the oxyallyl substructure and This contains three main aspects: (1) Synthesis of attribute the NIR transition and the NLO activity to this mixed metal oxide catalysts, (2) physicochemical substructure, which is common in all these molecules. characteristics of the active catalysts and (3) evaluation Using valence bond (VB) theory, an analysis of a three- of the catalysts for steam reforming of bioethanol for state model of this substructure is carried out. It is

the production of H2. seen that the mixture of an intermediate diradical character and some zwitterionic character in the MOLECULAR MATERIALS molecule and a large coupling between these two VB a) Nonlinear Optics resonance forms is responsible for large „ values. This Role of the donor groups connected to the oxyallyl can be used as a design principle for increasing NLO central moiety (suggested to be a powerful acceptor) activity in oxyallyl derivatives. has been emphasized in the literature for tuning the absorption maxima and obtaining large NLO activity in c) Organic Light Emitting Devices (OLED) croconates and squaraine dyes which are oxyallyl With a general aim to make anthracene derivatives derivatives. A series of new croconate dye model multifunctional (n-type emitter) and also study their molecules with aniline and substituted anilines as strong suitability as electron transport layers for organic light donors to the oxyallyl ring are prepared. Using emitting diodes (OLED), and with a more specific experimental and theoretical techniques like UV-visible interest to understand the charge transport and packing spectra, degenerate four wave mixing (DFWM), density pattern in the solid state due to the rotating side rings, functional theory, time-dependent density functional synthesized and characterized six novel molecules in theory, and symmetry adopted cluster-configuration which the 9 and 10 positions of anthracene have been interaction (SAC-CI), characterized linear absorption, directly substituted by phenyloxadiazole groups. Detailed nonresonant third order optical nonlinearity, charge studies of these molecules were done including transfer, and excited states of these molecules. These photophysical, electrochemical, electroluminescent molecules have smaller singlet diradical character and studies and solid state structure determination through the absorption is not in the near-infrared (NIR), as other crystallographic techniques. The electron affinity is very reported croconates, but in the 440-480 nm range. There high, around 3.1-3.2 eV, and the ionization potential is is a larger charge transfer (CT) from the side groups to around 5.9-6.0 eV, comparable to the more commonly used electron transport electroluminescent layer Alq . the central ring in these croconates evident from SAC- 3 The studies reveal that the new molecules being CI calculations compared to CT in NIR croconates. reported, in addition to the high thermal stability, are This clearly supports the model that the NIR absorption quite efficient in a two layer unoptimized device with in oxyallyl derivatives is correlated to the singlet diradical the device structure ITO/ -NPD/our molecule/LiF/Al character and not to the donor capacity. The „ values and have an emission in pure green. They also show determined by DFWM experiments show large very high efficiency as electron transport layer in device nonresonant values of -2.4 to -5.3 10-32 esu, which structure ITO(120nm)/ -NPD(30nm)/Ir(ppy)3 doped is larger than that of similar squaraines suggesting that CBP(35nm)/BCP(6nm)/ 5(28nm)/Al(150nm). From these the larger oxyallyl ring size and diradical character in studies it can concluded that the anthracene derivatives croconates play the major role and not the donor groups. also have considerable potential as multifunctional It can be concluded that with a noncentrosymmetric layers and as electron transport layers in OLED. structure, tunable absorption (visible-NIR), and larger „ • values, these less studied croconate dyes are more Photochemistry and photophysics of meso- interesting and will have a major role to play than the substituted porphyrins, synthesis and

48 Biennial Report 2007-2009 Inorganic & Physical Chemistry

characterization of porphyrin nanoparticles Preliminary photophysical characterization has been (Sponsored by DST) done. All compounds shows high yield of trans(E) to The photochemistry of meso-substituted porphyrins have cis (Z) conversion of direct photo-excitation in LB film been analyzed in view to realize mechanistic aspects as well as in polymer matrices but shows 8-10 percent of proton coupled electron transfer reaction in porphyrin yield of cis (Z) to trans (E) via triplet sensitization based systems. These results will aid in understanding where as all the compound shows 80-90 percent yield of PCET reactions in other systems and also in of Z to E conversion in solution phase by triplet biological processes.The performed frontier molecular sensitization. We are taking serious effort to increase orbital calculations open the new way to address the Z to E conversion yield in solid state such that it fundamental issues such as proton coupled electron- can used to optical data storage devices. transfer processes, which play an important role in PS II as well as developing new nonlinear optical materials However, to test the optical data storage efficiency of and so-called organic metals. those compounds, designed the above experimental setup and construction is under progress. Successfully prepared porphyrin nanoparticles in an • innovative methods. The innovation of this modified • Construction of working Fluorescence Correlation ëreprecipitation methodí lies on the judicial selection of Spectrometer (FCS) (Sponsored by DIT) organic solvent and amount of porphyrin solution to be The main objective of this project to enhance instrument injected in the aqueous media. This improved method making skill of students and to work with their own will lead to produce organic nanoparticles of - making instrument to determine and realize the following conjugated systems easily and efficiently. Presently facts: (a) determination of binding constant, (b) exploring the possibility of potential application of determination of number of reacted molecules, (c) porphyrin nano-particles. determination of lingand protein interaction, (d) • Studies of photochemical isomerization of determination of protein folding ñmisfolding dynamics, anthracene acrylic derivatives in Self-Assemblies (e) DNA dynamics, (f) determination of particle size mono/multilaayers towards the development of and concentration, (g) determination of reaction kinetics. molecular device( BRNS) The main objectives of this project is to explore the mechanism of cis-trans isomerization process of freshly prepared anthracene acrylic derivatives in the solid state in the form organized mono/multilayer and or in polymer matrices in view to apply this system making optical data storage devices.

Successfully constructed Fluorescence Correlation Spectrometer with excitation source of 532 nm. This instrument can detect fluorescence of single molecule level and it worked based on confocal microscopic principle. A schematic as well as real picture of our spectrometer is given below. Using our FCS we have Prepared (LB) monolayer compatible different derivatives determined diffusion coefficient and molecular radius of of antharcene acrylic acid with variable C-H chain length Rodamine-B which matches well to the literature. and successfully transferred the Langmuir monolayer Presently we are planning to determine the size of of all compounds both E and Z forms from water-air fluorescent organic nanoparticles. interface onto hydrophobic quartz substrate by vertically raising (Z-type), dipping-down (X-type) and combination This instrument can be upgraded to the following of both (i.e. raising-up and dipping down) at 30 mN/m-1 instruments for doing state-of-art single molecule level constant surface pressure. spectroscopy in biophysical systems. (1) Fluorescence

Biennial Report 2007-2009 49 Inorganic & Physical Chemistry

Resonance Energy Transfer (FRET), (2)Fluorescence zeolites depends on the concentration and type of Lifetime Imaging (FLIM), (3) Fluorescence Lifetime counter-anion of the surfactant used. The catalytic Correlation Spectroscopy (FLCS), (4) Fluorescence properties of nanosized β-zeolites, mainly concerning Polarizing FCS, (5) Raster Scan Image Correlation the role of internal and external acid sites, were evaluated Spectroscopy. by the isomerization/cracking of hexane and phenol alkylation with 1-octene. • Innovative Environmental Catalysis: Novel Catalysts for Abatement of Volatile Organic Compounds • Oxyhalogenation of aromatic compounds (India-Argentina collaboration) Developed a novel systems to generate electrophilic The combustion of was studied on Pt supported halogen in situ from potassium halides, ammonium

on V2O5ñTiO2 samples containing different amounts of halides as halogen source and H2O2 used as oxidant

V2O5.. The platinum dispersion in Pt/V2O5ñTiO2 catalysts for the oxyhalogenation of aromatic compounds. increased with the V O loading but the activity for the 2 5 • Zeolite and molecular sieve catalyst deep oxidation of benzene exhibited an opposite trend. Benzene combustion was a structure sensitivity reaction Synthesized the annelated pyridines, 5-ethyl-2- promoted on larger metallic Pt crystallites which were methylpyridine and highly substituted pyridines using aliphatic compounds over zeolites. Synthesized preferentially formed when the V2O5 content in the sample was decreased. Similar experiments were also SeMCM-41, MoMCM-41 and WMCM-41.These catalysts performed on Pt-V catalysts supported on alumina and used for the oxidation of 2-methylnaphthalene to 2- mesoporous materials like SBA-15. methyl, 1,4-naphthoquinone and styrene to benzaldehyde. • Studies on Environmental Conscious Chemical Processes by Solid Catalysts (India-Japan The in situ synthesis and encapsulation of metallo- Cooperative Science Programme) octamethylcalix(4)pyrrole inside the pores of HMCM-41 and metallosalens in NaY zeolite.. The catalytic Synthesised several active and stable mesoporous performance of the synthesized materials were tested materials that can be used as catalysts and catalyst for the liquid phase oxidation of cyclohexene using tert- carriers for immobilization of metal ions and cationic butyl hydroperoxide as an oxidant. and the liquid phase clusters of multivalence metals to carry out hitherto oxidation of p-xylene using H O as an oxidant. unexplored hydrogenation, alkylation and esterification 2 2 reactions. Friedel-Crafts alkylation has so far been • Development of a Solvent Extraction Flow sheet achieved with inorganic Lewis and Bronsted acids to for the Separation and Recovery of Cobalt and prepare bulky alkylated phenols. Novel large surface Nickel from Sulphate Leach Liquors of Pacific area ordered mesoporous materials like MCM-41 are Ocean Nodules Using Synergistic Mixtures of found to be promising catalysts or carriers for alkylation Organophosphorus and Sulphur Compounds of phenolic compounds. However due to severe (Minerals and Materials Processing Division, KIGAM, deactivation, it is necessary to modify them by Daejeon, Republic of Korea) immobilization of other active species like metal triflates. Separation and recovery of cobalt from nickel was A similar situation arises with the esterification of long demonstrated using synergistic mixtures of TOPS 99 chain aliphatic acids with alcohols to produce high value as an extractant and Cynex 471X/ Cynex 301 as esters. The highly corrosive, hazardous and polluting synergist Optimization of process parameters such as mineral acids was replaced with novel eco-friendly equilibrium pH of aqueous phase, reagent concentration, catalyst. phase ratio, scrubbing, stripping and counter current Nanosized β-zeolites were synthesized using the dry extraction/ stripping simulation were studied. gel conversion (DGC) method with tetraethylammonium • Studies on Recovery of Rare Earths from hydroxide (TEAOH) as a structure-directing agent (SDA) Phosphoric acid using Phosphorus Based in the presence of the surfactants: Commercial Extractants and their mixtures (Indian cetyltrimethylammonium bromide (CTMABr), chloride Rare Earths, IRELTDC, Kollam) (CTMACl) and hydroxide (CTMAOH). The presence of Fertilizer grade phosphoric acid is produced industrially the surfactant in the synthesis gel creates a confined from rock phosphate mineral, which is a futuristic source environment and controls the formation of nanosized - for the recovery of rare earth metals. With this objective, zeolites with SiO /Al O ratios of 25ñ200. The β-zeolites 2 2 3 systematic studies on the solvent extraction solid phase have uniform particle sizes of 35ñ60 nm with large BET extraction (SPE) behavior of rare earth metals from and external surface areas. The particle size of the β- phosphoric acid medium similar to fertilizer grade

50 Biennial Report 2007-2009 Inorganic & Physical Chemistry

phosphoric acid using commercial organophosphorus iodochromones. This study was extended to N- based reagents was taken up. Tributyl phosphate has heteroatom functionalized alkynyl compounds for the showed potential application for the separation of. In cyclization. In this study, we have synthesized a series case of SPE method, it is possible to separate Lutetium of highly substituted 2-perfluoroalkyl-3-iodoquinolines by from other rare earth metals using Tulsion CH-96 resin. two different methods in good to excellent yields under Further studies on separation of metals in continuous mild reaction conditions. The scope of this methodology mode are in progress. is extended by using the resulting 2-perfluoroalkyl-3- iodo quinolines in Suzuki, annulation, dehalogenation • Separation of Platinum Group Metals (PGMs) from and carboxylation reactions. Antimalarial activity of the Spent Automobile Catalyst Leach Solutions. 2-perfluoroalkyl-3-iodoquinolines is discussed. In The objective of this study is to develop a process flow continuation of our studies in the synthesis of new sheet to separate and recover Pd and Pt from chloride heteroatom functionalized alkynyl compounds, we leach solutions of spent automobile catalyst by solvent started investigation on the synthesis of S-donor extraction technique using commercial metal complex substituted alkynyl compounds and their organometallic reagents. The composition of leach liquor used for the reactions with palladium salts. Achieved a highly present study contains about 500-550 ppm Pt & Mn, selective intramolecular thiopalladation by treatment of 150 ppm Pd & Cr, 1500 ppm Fe, 1000 ppm Ni and 3M o-SMeC6H4CaîCC(CF3)(=N-4-OCH3C6H5) with HCl. Among the various reagents tried, LIX 84I extractant PdCl (PhCN) in THF at 0 C to afford [(C H S-3- gave clear separation of Pd from others. Studies on Pt 2 2 8 4 )C(CF3)(=N-4-OCH3C6H5)Pd(Ï-Cl)]2. The mechanistic separation from Pd free solutions are in progress. implication of the results were studied with the aid of • Organometallics: low temperature 1H NMR and ATR-IR spectroscopy. The broad area of research deals with Organometallic FACILITIES Chemistry. Design, development and synthesis of various organometallic reagents and intermediates for catalytic as well as stoichiometric organic transformations is the main focus area. Summary of results obtained during the course of work.

Horiba Jobin Yvon Micro Raman spectrophotometer

Specifications Model: LABRAM HR Operational Aspects: MicroRaman spectrometer with integrated microscope with 10x, 50x and 100x • Design, synthesis and applications of new hetero- objectives; Focal length 800mm, He-Ne 633nm Laser , substituted alkynyl compounds in the cyclization Argon 514 nm Laser with Edge filters, Gratings 600 reactions (Metallocyclizations and Iodocyclizations) and 1800 grooves/mm, Spectral range 6-5500cm-1, Resolution 0.3cm-1 per pixel at 633nm with 1800g/ Methodology developed for the synthesis of new hetero- mm, Confocal coupling optics, Detector-CCD-1024*256 substituted alkynyl compounds based on coupling pixels reaction of alkynes and corresponding hetero-atom functionalized aryl halides using recyclable palladium Special Provisions: Motorized X, Y, Z stage, Gas detector catalysts. Initially, started the investigation on the for Photoluminescence measurements, facility for liquid coupling reaction of aromatic acid chlorides and alkynes sample analysis. to afford ynones in high yields. The subsequent Application: Characterization for Nanomaterials, cyclization of ynones induced by easily available I / 2 semiconductors, polymers pharmaceuticals, forensic CAN reagents at room temperature to access materials.

Biennial Report 2007-2009 51 Lipid Science & Technology

Lipid Science and Technology Division (Formerly Oils & oil reduces oil loss and produces less waste compared Fats) is recognized nationally and internationally as center to the conventional alkali refining process. However, for excellence in the area of lipid research with major physical refining of rice bran oil is not successful unless thrust to vegetable oils. Vegetable oil industry is one of the phosphorus content in the dewaxed oil is reduced the major industries in the world with a huge turnover next to <5 ppm as the residual phospholipids cause color to petrochemicals. Vegetable oils not only play a significant fixation in the final oil when it is exposed to higher role in nutrition but find use in diverse applications. The temperatures during deacidification. The enzymatic vision and goals of the Lipids Division mainly pertain to degumming process developed by IICT made physical Newer Processing Methodologies for Vegetable Oils, refining of rice bran oil a reality with the production of Nutraceuticals, Oleochemicals and Biodiesel. high quality refined rice bran oil with several added advantages [Indian Patent, 202379 (2006); US Patent Lipid Science & Technology Division has established a 7,494,676 (2009)]. Enzymatic degumming is an eco- good rapport with the Indian Industries and CSIR has friendly process, as it does not generate effluent water. recognized this Division as ìCentre of Excellence for Lipid IICT has transferred the process to 19 industries and Researchî with a special financial grant of Rs 170 millions. licensed to eight Project Engineering Companies The proposed Centre of Excellence is establishing three located in 9 states. This is one of the outstanding specialized Quality Control Laboratories for Vegetable Oils, projects of IICT in terms of its reach and impact on the Biodiesel and Lubricants and one Process Equipment Pilot Indian Vegetable Oil Industry. Plant during the 11th five year plan. This facility caters the needs of the Indian vegetable oil and allied product industry on par with the International Standards. The centre will also strengthen high quality research in several thrust areas which are relevant and contemporary to the needs of the Indian vegetable oil industries The centre for lipid research has also initiated several Human Resource Development Programmes like national seminars and refresher courses for the benefit of the vegetable oil and allied industry at regular intervals. During this period the following activities were organized: i. National seminar on food labeling & quality control of vegetable oils on March 1st, 2008 and ii. Refresher course on processing and analytical methodologies of oils and fats during August 18 - 22, 2008.

Lipid Science & Technology Division has made pioneering Enzymatic Degumming Unit contributions in upgradation of traditional processing methods and development of new technologies for • Biolubricants downstream products of commercial importance. The highlights of the work carried out during this period are Synthetic Aviation Lubricants: A consortium involving presented here. IICT, IOC R& D, NAL, HAL, GTRE & CEMILAC was formed with IICT as the nodal agency to develop indigenous APPLIED RESEARCH technology for synthetic aviation lubricants with the financial support of CHT (Ministry of Petroleum, Govt of India) to a • Enzymatic Degumming of Rice Bran Oil tune of 50% of the project outlay and the remaining from Rice bran oil is known as nutritious oil due to its CSIR, DRDO and the participating institutes. Extensive balanced fatty acid profile and presence of nutraceuticals experimental work was carried out at IICT in developing such as oryzanol, tocotrienols, tocopherols and the process for two base oils on laboratory and bench phytosterols with well-documented health benefits. The scale to obtain data for establishment of pilot plant. A majority of the nutritional components like oryzanol and specialized integrated pilot plant of 100 kg / batch capacity tocotrienols present in rice bran oil are being destroyed was designed, procured and erected at IICT for the or removed during traditional alkali refining while preparation of two base oils for synthetic aviation lubricants. physical refining process retains large part of these About 500 kg of both the base oils prepared in the pilot components. In addition, physical refining of rice bran plant in different batches after preliminary physico-chemical

52 Biennial Report 2007-2009 Lipid Science & Technology testing at IICT was sent to other participating institutes at Composition of major and minor constituents of regular intervals for evaluation. jatropha and karanja oil: Free fatty acid (FFA) and unsaponifiabl matter of jatropha oil was found to be in the Vegetable oil-based lubricants: Vegetable oils like castor range of 2-7% and 1-1.5% respectively. The neutral lipid, oil have been used as lubricants since ancient times. glycolipid and phospholipid contents of the jatropha oil These materials have better biodegradability than mineral samples were in the range of 96-97%, 0.7-1% and 1-2% oils and are also renewable. Vegetable oils have some respectively. The major phospholipids of jatropha oil were shortcomings, such as a higher pour point and a lower found to be phosphatidylcholine (PC), phosphatidyl- viscosity index than synthetic esters. They have a limited ethanolamine (PE) and phosphatidylinositol (PI). The viscosity range and lower oxidative stability due to the positional distributions of fatty acids in jatropha presence of unsaturated bonds. Therefore vegetable oils phospholipids were also determined [Journal of American as such cannot satisfy all the requirements of modern Oil Chemistsí Society, 86 (2009) p.197-200]. FFA and machine lubrication. Lipids group is very actively pursuing unsaponifiable matter contents of karanja oil were ranging research in the area of vegetable oil-based lubricants with from 3 to 5% and 2 to 2.3% respectively a main thrust to castor and karanja oils. Different classes of compounds such as: castor oil fatty acid- based estolide Studies on the pre-treatment of jatropha and karanja alkyl esters and their acetates; 9,10,12-triacyloxy oils: Jatropha and karanja oils contain various minor octadecanoic acid alkyl ester-rich fatty acid alkyl esters components that can affect the yield and quality of the mixture; a variety of polyols esterified with different fatty biodiesel produced. Efficient pre-treatment processes for acids like 10-undecenoic, undecanoic and karanja oil both the oils were developed to get an oil as a suitable fatty acids; fatty acid and vegetable oil-based epoxy and feed stock for obtaining good quality biodiesel. their derivatives etc. All the lubricant base stocks were Preparation of biodiesel from jatropha and karanja characterized for lubricant properties like total acid number, oils: IICT developed a continuous process for the hydroxyl value, viscosity, viscosity index, pour point, flash preparation of biodiesel from palm, sunflower, jatropha and point, copper corrosion tests, oxidative stability, hydrolytic karanja oils with International specifications by employing stability etc., The properties indicate their potential as different approaches. Based on this data, a process for promising lubricant base stocks for automotive, hydraulic, the continuous preparation of biodiesel using multi metal working fluids and other industrial fluids. Five patents feedstocks was developed for both esterification and have been filed based on the above work. transesterification and a continuous pilot plant with 10 kg/ • hr capacity was established at IICT. Efforts are also being Biodiesel made to prepare biodiesel from different feedstocks using Generation of data on physico-chemical characteristics heterogeneous catalysts and also using enzymatic of jatropha and karanja seeds and oils: Jatropha and reactions. karanja oils are projected to be the most important bio- diesel raw materials in India. As these were not cultivated in the organized sector, almost no data is available on the yield and oil qualities of different seed varieties. IICT is helping various agricultural and plant genetic research institutes like CRIDA, ANGRAU and NBPGR to generate data on yield and quality of oil from the seeds collected by them and to identify the best seed variety as a part of the project sponsored by Department of Rain Shadow Area Development, Government of Andhra Pradesh. More than 400 samples of jatropha seeds received from the above organizations were analyzed for their oil contents and physico-chemical properties. The oil contents of the jatropha seed samples analyzed were found to be in the range of 21 to 42% and mostly in the range of 32 to 35%. The major fatty acids present in the jatropha oils are oleic and Biodiesel Continuous Pilot Plant linoleic acids. Similarly more than 200 samples of karanja seeds were also evaluated. The average oil contents of the An alternate process for producing biodiesel from high karanja seeds were found to be in the range of 28-32%. FFA containing crude vegetable oils like jatropha and karanja

Biennial Report 2007-2009 53 Lipid Science & Technology was also developed using the following protocols. The to set up karanja-based biorefinery for the preparation of method consists of (a) Liquid-liquid Extraction (LLE) of the several value added products from the by-product streams crude oil with to remove the bioactive constituents, of biodiesel like oilseed cake and glycerol to make the polar materials, free fatty acids (FFA) etc., from non polar entire biodiesel process economically attractive. The main glycerides, (b) in situ esterification of the FFA present in objectives of the project are as follows: i. Isolation, the extract with an acid catalyst (c) transesterification of Characterization and Evaluation of Bio-constituents resulting oil (raffinate) using a base catalyst and separation including Karanjjn from Karanja Oil and Cake; ii. Utilization of glycerol and crude ester in basic medium, (d) purification of Karanja Cake for Value Addition with a Main Thrust to of crude ester by LLE to biodiesel meeting the international Protein and Starch Based Products; iii. Purification of Crude specifications. LLE is carried out in a specially designed Glycerol into Different Grades; iv. Preparation of 1,2- equipment either in batch mode or in continuous mode. Propane Diol, Crown Ethers and Dendrimers from Glycerol; [Indian and PCT Patents Filed]. v. Development of Lubricant Base Stocks and Additives from Karanja Oil and their Evaluation. IICT has successfully Screening of indigenous tree-borne oils as potential developed several products from the karanja oil, cake and raw materials for the preparation of biodiesel: The glycerol during the execution of the project. major two oilseeds chosen by various state governments as well as central government in India for the preparation Novel heterogeneous carbon-based acid catalyst from of biodiesel are jatropha and karanja. Both the crops are crude glycerol for the preparation of biodiesel: A novel being widely cultivated by the farmers throughout the heterogeneous carbon-based solid acid catalyst was country. The availability of these oils at the present moment developed from crude glycerol, which is a by-product of is negligible and the oil may be available in large quantities biodiesel process. This solid acid catalyst consists of after couple of years. It was, therefore, proposed to study small polycyclic aromatic carbon sheets with attached - the suitability of other minor oils, preferably the tree borne SO3H groups to afford a highly stable solid with a high oils of Indian origin, as potential raw materials for biodiesel density of active sites along with high-performance catalytic production. Accordingly, a detailed study on minor oils activity towards the esterification of fatty acids into biodiesel. namely mahua, nahor, kusum, palash, thumba, undi, The catalyst will be ideal for the esterification of fatty acid rubberseed, tobaccoseed, and jangli badam is being carried present in indigenous non-edible oils containing high free out to evaluate these oils as potential raw materials for fatty acid (FFA) in place of traditional acid catalysts like biodiesel. This study is sponsored by Department of sulfuric acid and there by avoiding generation of effluent Science & Technology, Government of India. These oils, if water and salts. The solid acid catalyst developed by IICT found suitable as raw materials for biodiesel preparation, is very stable and can be recycled several times. [Indian might be cultivated in an organized manner and it might and PCT Patents filed, 2007; ChemSusChem, 2 (2009) uplift the economic conditions of the villagers and p. 617-620]. The catalyst is being exploited for several particularly tribals in different parts of our country. other applications. Development of processes for value added products • Vegetable Oil-based Nutraceuticals from karanja oil and cake: Karanja (Pongamia glabra), Reduced calorie fats: Lipids group has developed two is a widely grown tree throughout India, especially in Andhra structured lipids (SL1 and SL2) for their application as low Pradesh and Karnataka. Karanja is an indigenous plant calorie fats in bakery and/or confectionary products followed and is being used in Ayurvedic medicine in India. by their sensory evaluation in collaboration with CFTRI, Eventhough, karanja oil-based biodiesel has potential as Mysore (nutritional evaluation) and Sri Ram Institute of an attractive alternative to diesel, the economic viability is Industrial Research, New Delhi (toxicological evaluation). not yet established. Hence, exploitation of the by-products SL1 was prepared with a content of 28-30% behenic acid of biodiesel industry like oilseed cakes and glycerol is the along with balanced composition of saturated, need of the hour to improve the overall economics of the monounsaturated and polyunsaturated fatty acids. SL2 biodiesel industry. With this background, IICT is executing contains omega-3 fatty acid (ALA) up to an extent of 5%. a project entitled ìIntegrated project for development of Metabolic studies conducted at CFTRI showed that the processes/technologies for value-added products from calorific value of SL1 and SL2 are 5.12 and 5.28 kCal/g karanja oil and cakeî with the financial grant of Department respectively. The DSC studies of SL1 indicated its suitability of Science & Technology, Govt. of India. IICT has initiated in the preparation of bakery products such as cakes and this project to encourage karanja-based biodiesel industry biscuits. Thus bakery fats can be fully replaced by SL1.

54 Biennial Report 2007-2009 Lipid Science & Technology

The nutritional studies indicated that structured lipids have simple enzymatic method for the preparation of stearic hypolipidemic effects. This aspect will be studied in the acid-rich PLs from soybean PLs using stearic acid and future long term studies in rabbits at CFTRI. Toxicological tristearin as acyl donors in presence of Lipozyme TL IM. studies of both SL1 and SL2 did not show any treatment Maximum incorporation of stearic acid (34.9%) into PLs related observable toxic effects. was achieved using stearic acid as acyldonor. Major amount of stearic acid was incorporated into sn-1 position of Diacylglycerol (DAG): 1,3-Diacylglycerol-rich oils exhibit individual phospholipids [J. Lipid Sci. & Tech. 40, (2008), similar taste and texture as that of triacylglycerol (TAG) p. 124-128]. oils. As DAG oils do not generate 2-monoacylglycerol (2- MAG) in the gut, the absorption and metabolism of DAG • Sodium Stearoyl-2 Lactylate (SSL) oil differs from that of TAG and help in the reduction of Sodium stearoyl lactylate (SSL) is a food grade obesity. Among the other advantages, DAG exhibits emulsifier used as a dough conditioner. It conditions physiological differences like lowering of postprandial the dough by strengthening the gluten protein network lipidemia and an increased proportion of fatty acid (FA) for better gas retention, improved texture, and increased being oxidized instead of stored. DAG (70-80%) containing volume. It may be used in many food products like cooking oil is being sold in few countries as health oil. bakery mixes, baked products, cake icings, fillings, Lipids group developed process for similar DAG-rich oil, toppings, juices, puddings coffee whiteners etc. In containing additional nutritional components like oryzanol, cosmetic industries, it is used as an anionic emulsifier tocopherol, tocotrienol etc, for commercial exploitation. for cream and lotions. IICT developed a process for Toxicology studies carried out at NIN, Hyderabad revealed sodium stearoyl-2-lactylate and transferred to M/s that DAG oil developed by IICT does not show any adverse Tripura Biotech Ltd., Hyderabad. effects and found to be safe. • Undecenoic Acid Enrichment of tocopherol and phytosterols from A continuous process for the preparation of UDA from soybean and sunflower oil deodorizer distillates castor oil was developed and successfully (DOD): Soybean and sunflower oil-based deodorizer demonstrated to M/s Jayant Oils and Derivatives Ltd., distillate is a rich source for tocopherols and phytosterols. Gujarat at 3 kg/hr castor oil fatty acid methyl esters. IICT has developed a process for the isolation of phytosterols The process know how package and a detailed design (95% purity) and tocopherols (70% purity) with 70% report (1 ton/ day plant) was transferred to the industry. recoveries and the technology is ready for transfer. • Preparation of phytosteryl ferulates: A process was Preparation of Industrially-important developed for the preparation of phytosteryl ferulates Oleochemicals from Sal Fat (synthetic oryzanol) using the phytosterols isolated from India has widely diverse varieties of oilseeds and tree deodorizer distillates of sunflower and soybean oil with borne oilseeds in particular. In this context sal fat, one about 95% purity. The product was evaluated for its of the non-traditional oilseeds with a typical saturated hypocholesterolemic effect in comparison with natural fatty acid-rich composition can be exploited for preparing oryzanol isolated from rice bran oil soap stock. The results a variety of oleochemicals. As a part of studies revealed that phytosteryl ferulates exhibited similar sponsored by Tribal Co-Operative Marketing hypocholesterolemic activity with that of natural oryzanol. Development Federation of India Limited, Govt of Inida, [Indian and PCT Patents filed, 2009). IICT initiated work for the exploitation of sal fat for the development of several value-added products like Honey like lecithin: Commercial soya lecithin exhibits hydrogenated fat, lubricant base stocks and surfactants. colour more than 18+ units (Gardner scale) mainly due to the presence of pigments such as chlorophyll and • Enrichment of Methyl Ricinoleate from Castor oil carotenoids. IICT has developed a process to obtain honey Methyl Esters like lecithin with a color of 12-14 units from crude soya An efficient process for the enrichment of methyl lecithin and the process was transferred to two industries. ricinoleate (MR) from castor oil fatty acid methyl esters Lipase-catalyzed preparation of stearic acid-rich (CME) containing 85-90% MR by liquid-liquid extraction phospholipids: Saturated fatty acid-rich phospholipids was developed. The method consists of (a) mixing of (PLs) are used for a variety of applications in biological the castor oil methyl esters in a refined vegetable oil in and pharmaceutical areas. The present study describes a a defined proportion (feed) (b) liquid-liquid extraction

Biennial Report 2007-2009 55 Lipid Science & Technology

(LLE) of the feed using an aqueous polar solvent to get used in several other industrial applications. Coconut an extract-1 and raffinate-1 (c) desolventization and oil contains high amounts of low and medium chain drying of the extract-1 to get a solute of enriched fatty acids and due to that, the oil easily solidifies methyl ricinoleate (96-98% pure with 80-90% yields) at about 18-22 C and melts at about 24-27 C and this (d) further continuing the liquid-liquid extraction of the is a negative point to use coconut oil for hair raffinate-1 with polar solvent at elevated temperature to applications. IICT has developed a process for the get an extract-2 containing MR with enriched normal reduction of freezing point by modifying the coconut methyl esters (e) and recycling the left over raffinate-2 oil by employing interesterification process. This work (refined oil) in the process. The enriched methyl was carried out with a financial grant of Coconut ricinoleate (96-98% purity) will be exploited for the Development Board, Govt. of India, Kochi. preparation of number of castor oil based Industrial INFRASTRUCTURAL FACILITIES CREATED products with better quality and properties. [Indian & As a part of Centre of Excellence for Lipid Research, most PCT Patents Filed]. of the equipment related to dedicated quality control • Specialty Fat Liquors laboratories for vegetable oils, biodiesel and lubricants were established during this period. Expeller unit (60-100 kg/ Different ingredients and additives required for the hr) and pilot plants (10-15 kg/batch) for degumming, formulation of specialty fat liquors were developed from bleaching, deodorization and dewaxing were also vegetable oils and allied derivatives by employing variety commissioned. A super critical extraction pilot plant (12 lit of reactions like sulfonation, phosphation and capacity) was established at IICT. transesterification in collaboration with Balmer Lawrie & Co., Ltd., Chennai. A catalyst-free cleaner process for sulfonation of PEG-Transester of vegetable oil was also developed • Eri Pupae Oil Eri silk is an important variety of non-mulberry silk known for its elegance and is produced primarily in the Northeastern states of India. Eri culture i.e., rearing of silkworm, Samia synthia ricini has been introduced in Andhra Pradesh making use of both castor and tapioca plants. The spent silk worm pupae from both the varieties are mostly thrown as agricultural waste or are used as chicken/fish feed. IICT has developed an integrated process for the drying of silk worm pupae, extraction of oil from dried pupae and refining of oil at Super Critical Extractor pilot scale in collaboration with Sericulture Department of AP State Government. Eri silk worm pupae oil can BASIC RESEARCH be projected as a potential nutraceutical as it contains Synthesis of lipophilic antioxidant: Although synthetic about 50% of linolenic acid (omega-3 fatty acid). antioxidants such as BHT and BHA are widely used as • Studies on Coconut Oil efficient food antioxidants, there is a growing concern about their safety because of their suspected action as promoters Generally coconut oil deposits sediment on standing in of carcinogenesis. Hence, in recent years most of the tanks after oil extraction using traditional expellers. research in the area of food and nutraceutical fields has The sedimentation is a serious problem for coconut oil been focused on the use of antioxidants from natural producers and affects the market as the oil is not products. Phenolic acids are widely known to act as accepted with sedimentation. IICT has developed a efficient antioxidants. However, in spite of the potential process for the preparation of clear oil by separating health benefits of these phenolic compounds, many of the sediments from the crude coconut oil. them exhibit low solubility in hydrophobic media, which Coconut oil is an important oil used for both edible and affects their effectiveness as antioxidants in fats and oils. non-edible purpose. Its main non-edible use is in making Modification of these phenolic acids into lipophilic of soaps and use as hair oil and in addition, it is also candidates can be used as tool to enhance their solubility

56 Biennial Report 2007-2009 Lipid Science & Technology and miscibility in oil based formulations and emulsions. Synthesis of sulfated sodium salts of 1-alkylamino-3- Ferulic acid, one of the most abundant plant phenolic alkyloxy-2-propanols and N,N-di-(2-hydroxy-3-alkyloxy acids, was modified to lipophilic antioxidant molecule. A propyl) alkylamines as potential surfactants: 1- series of pseudo-triacylglycerol containing a pendant Alkylamino-3-alkyloxy-2-propanols and N,N-di-(2-hydroxy- phenolic moiety were synthesized by dihydroxylation of 3-alkyloxy propyl) alkylamines were prepared with the same side chain double bond followed by esterification. The chain length both for alkyl amino and alkyloxy groups by synthesized compounds of varying chain lengths were condensation of alkyl glycidyl ethers with long chain evaluated for antioxidant as well as antimicrobial activity alkylamines by employing thermal and microwave-assisted (Eur. J Lipid Science & Technol. 110, 1175-1182, 2008). methods. These compounds were further sulfated and evaluated as their sodium salts for surfactant properties Synthesis of wax esters: Wax esters are an important namely surface tension, critical micelle concentration, class of fine organics that have wide industrial utility. Most emulsifying property, wetting, foaming power and calcium of these long chain wax esters are of high melting point tolerance. Sulfated 1-dodecylamino-3-dodecyloxy-2-propanol and are poorly soluble in many commonly used organic and sulfated N,N-di-(2-hydroxy-3-dodecyloxy propyl) solvents. To overcome the extraction related problems and dodecylamine, were found to exhibit superior surfactant also to fulfill the advantages of liquid-liquid biphasic properties among the respective series of monomers and dimers [J. Surf. Det. 12, 117-123 (2009)] catalysis, the synthesis of wax esters was conducted in a Lewis acidic ionic liquid, choline chloride.2ZnCl by 2 Production of Gamma-linolenic acid from microbial reacting equimolar amounts of acid and alcohol at 110 C. sources: There is an increasing demand for an alternate A series of long chain wax esters (maximum chain length source of polyunsaturated fatty acids (PUFAs) due to C44) were synthesized efficiently using this protocol. The several positive health benefits attributed to them. The reported reaction system has the advantages of both objective of the work was production of microbial lipids homogeneous and heterogeneous catalysis with high with a main thrust to Gamma-Linolenic acid (GLA) while product yield and the ease of product as well as catalyst screening different microbial strains as an alternate source separation without the use of organic solvent (Tetrahedron in collaboration with NIIST, Trivandrum. After identification Lett. 2007, 48, 6962-6965). of strains, fermentation conditions in the laboratory was optimized for maximum formation of GLA in the identified Synthesis and evaluation of new monocationic gemini strains. Total lipid obtained from different strain was also surfactants: A series of monocationic heterocyclic thoroughly characterized. The strain, Mucor zychae MTCC conjugated lipids and their gemini counterparts were 5420 was identified as potential strain and its fermentation synthesized by varying the chain length of the hydrophobic condition was optimized for maximal production of GLA tail and also by inclusion of functional groups, such as [App. Biochem. Biotechnol. 151 (2008) p. 599-609 and ester and amides and also by varying the chain length of 152 (2009) p. 108-116]. Enrichment of GLA in the total the spacers. Synthesis of a series of compounds with lipid, after converting them to fatty acid ethyl ester was rigid and flexible spacers was also conducted. Initially, also carried out following urea crystallization method. Two synthesis and evaluation of imidazolium-based mono stage urea crystallization processes was highly efficient cationic surfactants with and without ester/amide functional for the extraction of fungal lipids as it resulted tenfolds group in the hydrophobic chain was carried out and their increase in GLA with a GLA recovery of 69%. By altering micellar properties were evaluated (Eur. J. Lipid Sci. the ratio of urea, ethanol and fatty acid esters (FAE), the Technol., 111, 941-948, 2009). Ether functionalized purity could further be increased (Food Research aromatic hydrophobic tail group of different alkyl chain International, Published online, 2009). lengths were synthesized and evaluated for micellar sodium/diphenyl hydantoin (DPH), used for treating properties. Influence of hydrophobic chain lengths, spacer epileptics & neuro surgery patients is a well known chain length, and type of spacer (flexible or rigid) on mutagenic, caricinogenic and teratogenic agents. Essential micellar properties of gemini surfactants such as surface fatty acids, especially the GLA was found to be the most tension, cmc, minimum surface area per molecule etc effective in protecting against DPH-induced genetic damage was studied. [Prostaglandins, Leukotrienes and Essential Fatty Acids, 80 (2009) p. 43-50]

Biennial Report 2007-2009 57 Organic Coatings & Polymers

BASIC RESEARCH effective immobilization of palladium nanoparticles. Using water, the green solvent, is an integral part of a • Hyperbranched Polyurethane-Urea/Silica Based chemical manufacturing process. Therefore, it is of great Hybrid Coatings importance to develop a reusable and ligand-free catalytic Organic-inorganic hybrid materials have attracted much system for SM reaction in the aqueous medium. attention in recent years due to their distinct A facile and simple approach was followed to synthesize combination of properties, both inorganic and organic poly (N-isopropylacrylamide-co-potassium methacrylate) components. These materials provide transparent hydrogel-nanocomposites (Pd@GEL). Among the coatings with much improved mechanical properties. composite gels with variable PMA contents, Pd@GEL5 These are prepared by sol-gel processes with its (PMA 1.6 mmol) exhibited best gel integrity, and associated mild conditions and tunable structure. A optimum Pd and water uptakes. It was tested for the series of organic-inorganic hybrid coatings from catalytic performance in Suzuki-Miyaura reaction. The hyperbranched polyurethanes (HBPU) were prepared catalyst was reusable 5-6 times without loss in its using hyperbranched polyester and 3- activity. The advantages of the present protocol are aminopropyltriethoxysilane. These hybrid coatings have mild, efficient, environmentally benign, ligand free been characterised for mechanical, thermal as well as reaction conditions using water as solvent, operational viscoelastic properties. The results show that inorganic simplicity, and high product yields. content can have a significant effect on the mechanical • and thermal properties of hybrid coatings. Atom Transfer Radical Polymerization • Controlled radical polymerization technology, which Chromate Free Water based Anticorrosive Sol-Gel includes atom transfer radical polymerization (ATRP) Coating on Galvanized Iron has evolved to be one of the most successful methods IICT has developed chromate free water based for the synthesis of polymers with precise control over anticorrosive sol-gel coatings on Galvanized Iron the structure of the resulting polymer, and the ability to conforming to the requirements of global environmental create complex structures like comb, brushes and stars conservations and specification. These coating of about with narrow polydispersity. Moreover, ATRP is very five microns thickness gives the corrosion resistance robust in tolerance of many functional groups, thereby of about 500 hrs in salt spray test as per ASTM B-117. permitting the controlled synthesis of a broad range of This is environmentally friendly thin organic coating functional polymers. IICT is in the process of developing (water based as well as chromate free). organic / inorganic hybrid materials and hydrophilic block having relatively hydrophobic block well defined • Highly efficient and Reusable Hydrogel Supported copolymers with varying structural complexity on Nano Palladium Catalyst : Evaluation for Suzuki- nano-, meso- and microscopic dimensions by ATRP Miyaura Reaction in Water method. Most of the catalysts used in SM reaction are based on palladium phosphine complexes or homogeneous APPLIED RESEARCH nickel which are difficult to recover. Therefore they are • Fluoroelastomers for Plastic Bonded Explosives economically and environmentally undesirable. Whereas Application: phosphine ligands are toxic, expensive and suffer from the contamination of the ligand residue in the final Plastic Bonded Explosive (PBX) is an explosive material products. In recent years, there has been an increasing in which explosive powder is bound together in a matrix interest in heterogeneous catalysts, which are easy to using small quantities of a synthetic polymer. PBX recover and reusable in the aqueous medium for several imparts several advantageous properties to the explosive cycles. Catalytic activity of palladium (Pd) nanoparticles like, rendering the munitions insensitive to accidental is found as one of the significant frontiers of research and intentional threats, overcome operational constraints that can avoid the formation of phosphines as byproducts like thermal, mechanical and ageing, and provide top in the reaction. In this context, functional resins are level performance. Fluoroelastomers are found to be considered to be intelligent supports for the very useful as PBX. Chlorotrifluoroethylene based immobilization of palladium nanoparticles. Due to their polymers are synthesized and are being explored for fine tunabiltiy of nanostructure chemical and thermal this purpose as PBX material. stability along with good physico-chemical properties • Synthesis of Glatirameracetate (Sponsored by make them attractive and environmentally friendly Biocon, Bangalore) catalysts. Macro-reticular (permanent porosity) and Glatirameracetate is a synthetic polypeptide used for gel (nano-porous in swollen state) type of treatment of multiple sclerosis. A new process for its macromolecular resins are extensively explored for synthesis is being developed.

58 Biennial Report 2007-2009 Coal, Gas & Energy

The major activities of coal, gas & energy division are coal The objectives of the project are for generation of gasification, gas purification/separation, hydrogen hydrogen from biomass derived glycerol. The programme generation and characterization and analyses of fuels. of work involves two phases. First phase consists of • catalyst development and bench scale experimentation • 50 KW fuel cell power pack with methanol as for generation of kinetic data for scale up. The second primary fuel (Sponsored by MNRE, New Delhi) phase involves design, fabrication and operation of 3 IICT developed a methanol steam reformation system hydrogen generation unit at 2 Nm /h of hydrogen capacity. MNRE sponsored the first phase work. for hydrogen generation. IICT designed the 50KW Depending on the success of first phase, MNRE agreed reformer and all its subsystems based on the design to support the second phase programme. The catalyst data collected from IICT 10KW reformer. The feed heating screening and bench scale studies are in progress. system consists of preheating, vaporizing & superheating • zones and gas clean up section. Specifications were Development of process for medium temperature prepared for all the necessary equipment. Trasntech contaminant clean up of coal derived fuel gases (Collaborative project between IICT & BHEL (R&D), Projects Pvt. Ltd., Pune, fabricated the unit. 2x5 kW Hyderabad) PEM fuel cells are being procured from SPIC Science Foundation, Chennai to integrate with the reformer. Coal gas is a multicomponent mixture of fuel gases

Commissioning and testing of the 50 kW methanol and also consist of minor impurities like ammonia, H2S, reformer is in progress. alkali vapour and other trace impurities. These impurities result in the formation of undesirable contaminant gases on combustion, which pollute the environment and corrode the downstream process equipment. Hence, the purification becomes necessary, before it is combusted in the gas turbine. The conventional process of wet scrubbing for purification of coal gas is not efficient as this process involves cooling of coal gases coming out of gasifier, which results in loss of thermal efficiency. Instead, the hot gas cleanup when adopted results in improving the thermal efficiency by two percentage points. This hot gas clean up was done at bench scale level earlier with the sponsorship of ministry of coal. Based on the success of this study, BHEL (R&D) has come up with a collaborative program. The objective of this collaborative project is to develop a process to remove contaminants such as ammonia, sulphur compounds and alkali in coal gas, generated 50 kW Methanol Reforming Reactor set-up from a pressurised fluidisized bed gasifier (PFBG) at • Generation of hydrogen from biomass derived 20 kg/cm2 and medium temperature (350-5000C) glycerol (Sponsored by MNRE, New Delhi) conditions. Glycerol is major by-product during bio-diesel production The programme involves carrying out experimental by transesterification of vegetable oils. To make the studies jointly by IICT & BHEL, utilizing the infrastructure bio-diesel process economically more attractive this & analytical facilities available at IICT, to study the crude glycerol can be efficiently utilized to generate removal of individual components in coal gas such as hydrogen. There are many reforming techniques such sulphur compounds ammonia and alkalis separately as auto thermal reforming, aqueous phase reforming, using suitable adsorption techniques and later the gas-phase steam reforming and conventional steam removal of all the above three component. These will reforming. Out of these, steam-reforming technique was be tried in tandom, thus leading to comprehensive clean found to be convenient to produce hydrogen from up. glycerol. However, the steam reforming reaction of these Analytical Services bio-oxygenates is often accompanied by the formation The division undertakes characterization and testing of of various by-products, reducing the selective production different fuels as per ISO 9001:2008 standards. Our clients of hydrogen. By using the appropriate catalysts by include Singareni Collieries, BHEL, Stewart & Lloyds product formation could be minimised. Surveyors, etc.

Biennial Report 2007-2009 59 Chemical & Instrument Analysis

Analytical Chemistry Division (ACD) is a centralized Impurity profiles of tamsulosin, olanzapine, , multifaceted facility with sophisticated and state of art coenzyme Q10, mirtazepine, phenazopyridine HCI, analytical equipments for Chemical & Instrumental analysis. and . Counter current extraction, The division provides qualitative and quantitative analysis isolation and detemination of solanesol in Nicotiana services to R & D projects of the laboratory and also tobaccum L. by non-aqueous rversed-phase high caters analytical services (ISO9000) to the chemical performance liquid chromatography was also stuided. industry, universities and other research institutions. X-RAY CRYSTALLOGRAPHY The division activities are grouped into the following areas: X-ray powder diffraction (XRPD) is a rapid, non- ❖ Chemical Analysis destructive analysis technique primarily used for phase ❖ X-Ray Crystallography identification of a crystalline material. This technique provides a qualitative and quantitative picture of ❖ Mass Spectrometry crystalline materials in geology, environmental science, ❖ NMR Spectroscopy material science, engineering and biology. X-ray CHEMICAL ANALYSIS crystallography centre is equipped with two powder X- ray diffractometers (Bruker D-5000 and D8-Advance with Sophisticated instruments: viz., Semi-preparative HPLC Linx-Eye detector), one Single Crystal Diffractometer with UV-Visible, photodiode, conductivity, fluorescence, (Bruker Smart APEX). electrochemical and evaporative light scattering detectors, Hewlett Packard GLC, Perkin Elmer AAS, UV-Vis-NIR Spectrometer, Camag HPTLC, Micro Cube Elemental Analyzer, Capillary Electrophoresis (PrinCE- D-750) are available. R&D services are also provided in impurity profiling, drug master files (DMF), chemical equivalence, method development and validation, chiral separations, environmental analysis, analytical and preparative isolation of compounds, residual analysis of pesticides and drugs. It also provides facilities for bioanalytical, micro separations and on line 2D LC separations. Several consultancy projects for industries, institutions and universitis for quality assurance, kinetic studies and stability tests have been taken up. The projects include: Characterization of water soluble polymers by GPC, M/s. SNF Pvt. Ltd., Hyderabad; Development of analytical methods for transformer oils for M/s. BHEL The Centre provides its expertise in structural R&D, Hyderabad; Estimation of Genopep in serum characterization of inorganic and organic compounds extracts by HPLC, Osmania Medical College, to various divisions of the laboratory. In the area of Hyderabad; Phase I Clinical trials of Genopep, Gandhi Medical College, Hyderabad. The division is presently involved in a CSIR Network Project on Certified Reference Materials. Value chain model for production of bioethanol from sweet sorghum is yet another project, from ICRISAT, Hyderabad. We are also undertaking an accelerated stability evaluation of Genopep, a peptide undergoing the clinical trials for development of new drug for the treatment of burns, from M/s. Issar Pharmaceutical Pvt. Ltd., Hyderabad. The chemical analysis group has provided services to Singareni Collories, Kottagudem by analyzing coal ash and coal samples. Some of the basic scinence activities of the group are:

60 Biennial Report 2007-2009 Chemical & Instrument Analysis

drug-polymorphism, this centre extends facility and demonstrated that the CID study of the protonated, expertise to various drug industries in the country using deprotonated and cationized peptides provides a method Powder (XRPD) and Single Crystal techniques. During to distinguish positional and diastereomers of these this period, XRD centre has successfully completed peptide isomers. around 25 projects which are related to drug-polymorphic ESI and APPI tandem mass spectrometry studies. It is one of the best centres of the laboratory techniques were shown to be very useful for with very substantial earnings, and with 30 research distinguishing the diastereomers of Oppolzer sultam publications in various International Journals. derivatives. A novel intramolecular benzyl migration was This centre also has one X-ray Fluorescence (XRF) observed in these protonated ions, which was supported Spectrometer, funded by DST for the characterization by tandem mass spectrometry, high resolution, of metallic contents in herbal medicines and provides deuteration studies and by comparison with an authentic support to the in-house projects as well as industries, reference sample. academia and research institutions in characterizing Diastereoselectivity in the McLafferty rearrangement the powder/liquid compounds for their constituents, right of protonated precursors of belactosin derivatives, using from ppm to percent levels. ESI and atmospheric pressure photo ionization (APPI) A project report on ìCharacterization of Indian Ayurvedic tandem mass spectrometry, was used to differentiate a drugs for their heavy metalsî is being prepared for pair of diastereomers of belactocin precursors. publication. Gas-phase Nazarov Cyclization of protonated 2- methoxy and 2- hydroxychalcone to produce protonated 3-arylindanones was studied using ESI tandem mass spectrometry and computational studies. This is a good example of intramolecular Proton-Transport Catalysis. Neutralization-reionization mass spectrometry in combination with other tandem mass spectrometric techniques and theoretical calculations were used to study some reactive intermediates such as thioketene and its isomers, ionic and neutral mercaptothiocarbonyl, and OCCO+, NNCO+, NNNN+ radical cations. Iodinated tyrosines were developed as chiral references for discrimination of D- and L-amino acids MASS SPECTROMETRY under electrospray ionization conditions. Effect of iodine substituents in the chiral reference towards chiral Mass Spectrometry centre of IICT achieved the discrimination was also studied. The study was certification by OPCW as an OPCW Designated extended to discriminate the amino acids using halogen Laboratory. This distinction is conferred on very few substituted phenylalanines as chiral selectors and also laboratories in the world (less than 20 labs have the to study the effect of halogen. designated status). IICT is only the second lab in the country with this status. Recertification of NABL Natural mononucleotides were explored as fixed ligands accreditation of the lab was performed in accordance towards chiral discrimination of hexose with the ISO/IEC/17025:2005. monosaccharides by the kinetic method. In this method, chiral discrimination was achieved by The following basic research investigations were investigating the collision-induced dissociation spectra undertaken during this period: of trimeric complex ion, [NiII(FL)(ref)(A)ñH]+ generated Electrospray ionization tandem mass spectrometry (ESI by electrospraying the solution mixture of D- or L-hexose MS/MS) was used to study the mass spectrometric monosaccharide (A), fixed ligand (FL), amino acid (ref)

behavior of a series of peptides derived from non-natural and NiCl2. amino acids containing sugar groups. The following Previously, we had reported GCA as chiral auxiliary for peptides were investigated: i) phenylalanine-β3-h-valine/ the enantiomeric differentiation. This study was further β3-h-valine-phenylalanine, ii) L-Ala-γ4Caa / γ4Caa-L-Ala-, performed on tetranucleotides that were extended iii) Boc-β,γ- and γ,β-hybrid peptides iv) GABA- hybrid versions of GCA at 3í and 5í end. GCAA and GGCA peptides and v) aminoxy hybrid peptides. It has been showed chiral discrimination of amino acids, but reverse

Biennial Report 2007-2009 61 Chemical & Instrument Analysis

selectivity. Binding constants of 1:1 complexes were one of the studies, the influence of the size of the also studied for better understanding of the stabilities sugar ring on the robustness of the 10/12-mixed helix of diastereomeric complexes. was investigated. Employing the concept of alternating chirality, oligomers containing galactopyroside and homo Gas phase acidities of deoxyribonucleosides were C-linked carbo-β-amino acid (β-hCaa), showed that the measured for the first time by applying the extended larger side chains reduce the helical stability. In yet kinetic method using substituted aromatic acid/phenols another study the monomeric β-Caa unit was modified as the references. The experimentally estimated values to have an amine group at the C-1 position of the were in good agreement with those obtained at B3LYP/ lyxofuranoside side chain, to obtain water soluble 6-311+G**//B3LYP/6-311G** level of theory. The oligomers. These peptides displayed moderate anti- theoretical calculations also helped to predict the most bacterial activity and had 10/12-mixed helical structure preferred deprotonation sites in these in CDCl solution. However in water, these helices were deoxyribonucleosides. 3 destabilized and no definite structure could be Diastereomeric synthetic precursors of isofebrifugine and deciphered. On the other hand, oligomers from β-Caa, febrifugine, natural alkaloid with potent antimalarial containing C-difluorophenyl moity at the anomeric carbon activity, were differentiated by electrospray ionization in the modified lyxofuranoside side chain, did not display tandem mass spectrometry. Stereochemical and any biological activity, inspite of having a 10/12-helix. substituent effects towards diastereomeric Short nucleoside derived β-amino acid (NSA) discrimination were also studied. homooligomers, obtained from azido thymidine (AZT), Structural characterization of a series of meso-dialkyl, were found to adopt right-handed 12-helical structure alkyl aryl and cycloalkyl calix(4)pyrroles was established (Figure 1) with their bases positioned systematically under positive and negative ion tandem electrospray along the helix axis. Oligomers comprising of ionization (ESI). Dissociation studies of all the ions enantiomeric cis-oxo-β-norbornene amino acid [2R,3S] revealed the arrangement of sub groups. Isomeric meso- and [2S,3R] residues at alternate positions were shown cycloalkyl compounds and N-confused calix(4)pyrroles to generate robust bend-strand secondary structures, showed differential [M + Na]+ ion yields. Isomeric with consecutive 6-membered turns. methyl and hydroxy phenyl calix(4)pyrroles showed specific fragmentation pattern in the dissociation of [M - H]- ions. NUCLEAR MAGNETIC RESONANCE (NMR) SPECTROSCOPY The NMR centre activities cover two aspects of research and development. The emphasis has remained towards the study of the molecular structure, conformation and dynamics of peptides, peptidomimetics and novel organic molecules and providing very crucial support to various R&D projects of the institute. Design of the Figure 1: NDA foldamers, with amide modification on the peptide scaffold mimicry, utilizing the conformational backbone of AZT. restrictions, amide bond isosteres, modifications of native peptide backbone etc., was undertaken on NMR studies also showed that mixed peptides, peptides containing higher homologues of α-amino acids containing α-, β- and γ-amino acids alternatingly, and their hybrids. The activity in this area encompasses enhance the size of the the ìfoldamerî domain several linear, cyclic and pseudo-peptides. fold. In continuation of this philosophy, α/δ-peptides δ δ The oligomers of β-aminoacids, the β-peptides, generate containing alternating -Ala and C-linked carbo- - δ a large number of well defined structures. Such folded peptides ( -Caa) were studied. In conjunction with the structures are known as ëfoldamersí. Earlier work in the theoretical studies, it was demonstrated that these group had shown that as few as three residues are oligomers result in 13/11-helices. It was rather interesting δ sufficient to stabilize a robust helix in oligomers to find that in spite of the flexibility of the -amino containing C-linked carbo-β-amino acids (β-Caa) and acids, constrained values of dihedral angles are preferred furanoid-cis-β-sugar amono-acids (Saa). During this about the C-C bonds. period oligomers with new β-Caa, were investigated. In To create skeletal diversity by replacing the Cα and/or

62 Biennial Report 2007-2009 Chemical & Instrument Analysis

Cβ atom in β-amino acid and Cα, Cβ and/or Cγ atoms well defined intra-molecularly hydrogen-bonded in γ-amino acids with heteroatoms, leading to new class structures with distorted ìβ - β cornerî motif, similar to of compounds, is an interesting strategy for attaining a a tennis ball seam. variety of secondary structures. Yang et al. have shown Structural analysis of the di-O-caprylated glucose- that the oligomers of α-aminoxy acids (α-AA), an oxa derived furanoid amino acid (6-amino-2,5-anhydro-6- analogue of β-amino acid, generate a very robust 8- deoxy-D-gluconic acid, Gaa) containing analogue of the helix. Similarly the oligomers of β-aminoxy acids (β- receptor binding inhibitors of vasoactive intestinal peptide AA), generate a very stable 9-helix. From our studies, established a well-defined beta-turn structure with an we have provided overwhelming evidence that the 10/ intramolecular hydrogen bond. 12-helices dominate in oligomers of β-Caa. It was therefore felt worthwhile to investigate 1:1 mixed peptides In view of the importance of helix-turn-helix (HTH) containing δ-Caa and α-AA alternatingly, to explore the structures in various recognition processes in biology, conformational control and preferences of these rather we had earlier demonstrated a successful design with different residues. It was found that the conformational as few as 11 residues, using short robust mixed helices dominance of β-Caa prevails over those of α-AA to from β-peptides. In the foldamer domain such tertiary yield 10/12-mixed helices. We have also undertaken structures are also referred as ëtyligomersí. In yet another studies on short oligomers of cis-β- furanoid sugar novel and serendipitous discovery, while studying aminoxy acids (β-fAA), a new class of γ-amino acids. peptides with alternating α- and β-amino acid residues Unlike the observation of Yang et al, these peptides (α/β-peptides), we found the nucleation of a novel three exhibited rigid ribbon like secondary structures residue turn, initiated by an 11/9-helix at the N-terminal. stabilized by 5/7-bifurcated intramolecular hydrogen Unlike our earlier observation of an11/9-helical structure bonds (Figure 2). in α/β-peptides, with ëα-β-αí motif at the C-termini, it was observed that when the C-termini contain the ëβ-α- βí motif, they from a rare three residues turn, while a helix is retained at the N-termini, thus generating a helix-turn (HT) super-secondary structure. We further used these HTs by appending short α/β-peptides at the C-termini (having a β-Caa at the N-termini), to design HTH structures. It was interesting to note that, though the extension of the HT by the short peptides perturbed the original turn, a new three residue turn was generated, with ëα-β-βí motif, yet retaining an HTH tertiary structure, Figure 2: Ribbon like structure in β-fAA oligomers, with as few as 9 residues (Figure 3). stabilized by 5/7-H-bonds.

Turns and loops are crucial in designing super- secondary structures. NMR studies on short linear peptide containing a pyrrole amino acid (Paa) and a furan amino acid (Faa), were carried out to demonstrate that they adopted a well-defined β-hairpin structure. The conformational control of a 14-helix nucleating template, cis-β-furanoid sugar amino acid, over a flexible δ-amino acid, ornithine was studied in a cyclic tetrapeptide. It was revealed that a three-dimentional bowl-shape cavity is stabilized by 5- and 7-membered intra- and inter-residue H-bonding, in polar and non- polar solvents, respectively. C2-symmetric 24 membered macrocyclic cationic anribacterial peptides containing Figure 3: Stereoview of the HTH motif. δ-sugar amino acids were investigated. NMR studies clearly brought out the ampiphilic nature of these These successes in designing two novel HTH motifs, bacteriolytic peptides, with low hemolytic activity. Like with so few reported in the literature, will lead to our earlier studies, these cyclic molecules displayed glimpses in the wide horizon of designed artificial

Biennial Report 2007-2009 63 Chemical & Instrument Analysis

proteins. We can conceive functional proteins, Several novel organic molecules were investigated and appropriately decorated with various functional groups their structures derived for understanding and validating in such scaffolds, derived from foldamers and the findings of a number of methodologies, which helped tylogomers. in the delineation of the subtle intricacies of the reaction mechanisms. Specially noteworthy was the effort in Double helical structures in peptide domain are rare fixing the stereochemistry of the ABCD ring framework and have been observed only in the gramicidin and of Azaspiracids, obtained by an stereoselective their structural analogues. We found that mannose- synthesis. Detailed NMR studies were also undertaken derived sugar amino acid (Maa), with its 2,5-trans on azumamide E and azumamide E-Saa analogues. configuration, imposes a conformational bias, such that Annulated pyrroles and bicyclic aminols, obtained from the oligomers of Maa(Bn )-Phe-Leu generate head-to- 2 InCl3 catalyzed three component reactions, containing tail dimers with a double helical structure (Figure 4). sugar, aryl amine and acetyl , were studied in detail. NMR studies were undertaken in the design of bihelical structure, using diphenic acid as conformational lock. Work carried out in collaboration with NGRI, Hyderabad, showed for the first time the presence of the natural, high pressure and temperature (HPT) phase of fullerene

(C60), in the iridium rich layers of the intertrappean sediments of Anjar. Conditions of the high pressure and temperature required for the formation of HPT phase of fullerenes can be created by an energetic impact event. Therefore, the presence of HPT fullerene in the Cretaceous-Tertiary (KT) boundary layer at Anjar is linked to the impact event at the KT transition. In yet another study, it was shown that saponite obtained from Deccan Flood basalt at Killari is capable of reducing the Cr(VI) to Cr(III). The saponite thus could be useful mineral in the environmental management of areas affected with Cr(VI) effluents. Figure 4: (A) Schematic representation of characteristic nOes in the dimer; (B) Stereo view of one of the low For the institutions working in the areas of chemical energy structures. science and technology, NMR Spectroscopy is an indispensable tool. Our facility supports a very large The dimeric assembly was found to be stabilized by number of R&D projects of the Institute. NMR group three centre as well as equal number of conventional provided spectra for more than 88,000 samples to the CO-NH H-bonds, across the strands. The unique users in the laboratory. As support to users outside the structures have a pitch of ~ 18 , a periodicity of 6 institute, spectra were also provided for about 2400 residues/turn and an inner diameter of ~ 1 . external samples during this period.

64 Biennial Report 2007-2009 Chemical Biology

Chemical biology is a scientific discipline spanning the with new molecules, exploring the roots in the genetic fields of chemistry and biology that involves the application pathways to find new therapeutic agents, validating the of chemical techniques and tools, often compounds results by genomic and RNA interfernce mechanisms and produced through chemistry, to study and manipulate studying proteins at the molecular level. biological systems. It is both the use of chemistry to MicroRNA based Therapeutic Approach advance a molecular understanding of biology and the harnessing of biology to advance chemistry. Current study focuses on microRNA based approach and provide some insight on molecular diagnostic of different CENTRE FOR CHEMICAL BIOLOGY complex diseases including cardiovascular disease and FaCBi is an integral part of the Center for Chemical Biology. Type II diabetes based on microRNA profile. Screening of The focus of the FaCBi is to provide the service and support numerous natural and synthetic molecule primarily in cell and target based screening and validation to facilitate categoried on disease potentials for anti microRNA acvity the identification of chemical tools to study biological is underway. These may become potential candidate to pathways and to discover lead compounds for the control the gene related to the disease. development of novel therapeutics. Biological Compatibility Studies of Drug Delivery The major objectives are: Vehicles ❖ To develop specific chemical and biological tools to Development of new organic biodegradable, non toxic nano further our understanding of a wide range of research carriers for tissue and organ specific delivery with special areas, such as., cancer, cardiovascular diseases, interest in siRNA delivery. diabetes and CNS disorders. Development of a Diagnostic Marker for Parkinsonís ❖ To develop novel drug targets, assay development and Disease screening studies. The etiology of Parkinsonís disease suggests a wide range ❖ Combinatorial approach for the identification of novel of biochemical manifestations ranging from oxidative stress signaling mechanisms and therapeutic stratagies. to increased cellular iron content, existence of familial mutations etc. However, there is one common denominator The core research facility contains laboratories for molecular i.e., a-synuclein protein, that culminates into the Lewy biology, analytical biochemistry, microbiology, cell biology, body formation which is a pathological hallmark of PD. By proteomics, and imaging. The facility is housed with faculty employing Parkinsonism mimetics (i.e., MPP+, rotenone) and researchers engaged in interdisciplinary research. It and related oxidants, we have identified a regulated process provides a platform for collaboration among many diverse of alternative splicing of a-syn mRNA, generating shorter academic and research disciplines to enhance discovery isoforms of protein by virtue of exon skipping. Development and encourage innovation. of a specific method to identify the spliced isoforms of a- BASIC RESEARCH syn could form a basis for the early detection of PD and also would enable us to understand the overall mechanism/ RNAi : Role in Chromatin Compaction s mediating PD pathophysiology. Chromatin consists of proteins that serve as the structural Role Of Mitochondria-Targeted Antioxidants In organizer of DNA, binding DNA into higher order structures Combating Parkinsonís Disease and ultimately forming the chromosome itself. The goal here is in elucidating the role of RNA interference in The selective degeneration of mesencephalic dopamine heterochromatin formation and cell division for finding the neurons (MDN) is one of the characteristic hallmarks of protein partners involved in the complex and characterizing the Parkinsonís disease (PD). Although the precise them with an aim in developing therapeutic ones. molecular mechanism(s) are not yet known, reports suggest that increased oxidative stress in the brain Finding New Therapeutic Agents and Targets mitochondria is responsible for the pathogenesis of PD. Thousands of compounds either natural or synthesized Several in vitro and in vivo studies, using MPP+ and rotenone, have the potential for therapeutic applications impacting demonstrate that these toxins can induce oxidative stress, many disease targets.†Here we have integrated the apoptosis and other biochemical changes similar to that of biological methods to merge small molecule and target PD. Our preliminary results indicate that Mito-Q and Mito- biomolecule research to allow for elucidation of disease Vit-E significantly inhibited MPP+-induced apoptosis in pathways and investigate drug mechanisms at the mesencephalic dopamine neurons. Further experimentation biochemical, molecular and genetic levels. Current on the plausible effects of these compounds on oxidative innovations are targeting the control of cell division in cancer stress, cellular iron accumulation,? a-synuclein aggregation

Biennial Report 2007-2009 65 Chemical Biology and dopamine levels indicate the potential use of these deacetylation patterns and their subsequent age specific compounds in combating PD. gene regulations and mitochondrial biogenesis of heart and other vascular cells during the ageing process. Role of Proteasome in Cancer Also the effects of certain caloric restriction mimetics The main objectives of this project is to study the detailed are studied to see whether they delay the ageing mechanistic aspects that leads to the mis-regulation of process. cancer cell proteasome, the biochemical alterations induced by the cancer cell proteasome and the efficacy of different Structural Biology of Drug Targets classes of proteasome inhibitors to combat cancer. Our Drug discovery studies are also under taken by this group. initial screening studies on the proteasome activities Chemistry, molecular, structural and cell biology, indicated that a majority of tumor cells possess altered cheminformatics, bioinformatics and structure based drug proteasomal activities compared to their normal cell discovery tools are used to understand the structure and counterparts. We have also identified a novel form of function of proteins, and to find effective inhibitors (drugs) immunoproteasome that happens to be a catalytic subunit in combating diseases. Our current focus is on a protein and an inducible isoform in a majority of cancer cells. subclass called proteases. Proteases play key role in a Presently, we are in the process of cloning the full length number of pathological processes. Inhibition of proteases gene of this novel isoform and identify whether this could can control diseases such as cancer, arthritis, bacterial become a specific target for the treatment of cancer. and viral infections. Role of Statins in Cancer Cell Death Cancer The overall objective of this study is to set down the Several proteases play important role in the development molecular mechanisms by which statins (HMG-CoA and progression of cancers. Despite the development of reductase inhibitors) exert cytostatic and proapototic effects drugs to various cancers, expensive treatment and non- in tumour cells. Statins primarily act by depleting isoprenoid selective drug targeting necessitates the need to search intermediates thereby dysregulating the prenylation of small for the new target proteins or improve the existing drugs. GTPases. Isoprenylation is an important post translational Studies are in progress for understanding the role of some modification required by GTPases for their varied biological cell surface proteases that degrade the extra-cellular matrix functions including proliferation, motility, cytoskeletal to promote the growth of tumors. integrity etc. Present work is mainly focused on delineating Microbial Infections isoprenoid-mediated molecular pathways responsible for tumour progression and metastasis involving both genetic Microbial related diseases like tuberculosis, influenza and and epigenetic events. pneumonia have evolved into new strains that are resistant to most of the available drugs. Microbial proteases labeled Role of Oxidative Stress in Atherosclerosis & as immunoglobulin A (IgA) proteases are involved in Cardiovascular Ageing destroying the human immune defense system during Atherosclerosis: Atherosclerosis involves the deposition pathogenesis. Those strains of microbes that lack IgA of fats, cellular metabolites, , calcium, and proteases are non-infectious suggesting that these could various other substances on the inner lining of the artery. be used as drug targets. Studies are in progress to In the present study, we sought to delineate the understand the molecular structure of these proteases and molecular mechanisms of oxidative stress-induced discover inhibitors that will hamper the ability of microbes vascular dysfunctions during the development and to infect the humans. Other studies include understanding progression of atherosclerosis. This is achieved by of protein-protein, protein-DNA and protein-RNA interactions studying individual or in concert roles played by either to establish a basic understanding of cellular endothelial, macrophages and vascular smooth muscle mechanism or to design small molecules to destroy such cells in response to various physiological oxidants and interaction to combat disease. their intricate relationships in disease progression. It is Chemical Biology Facility to Industry (Bioplus Life also of interest to study the therapeutic interventions Sciences Ltd., Bangalore) by means of targeted therapies to effectively combat IICT provided laboratory facility and consultancy services the plaque formation in both cell culture and knockout to an industry (Bioplus Life Sciences Limited, Bangalore) mice models. under PPP Programme for developing new product/ Cardiovascular Ageing: The goal of this project is to processes based on state of R&D techniques. myRNA.a understand the role of oxidative stress in chromatin new entity of Bioplus is engaged in carrying out R&D in remodeling and studying the methylation, acetylation the field of Biology, Molecular Biology & Genomics.

66 Biennial Report 2007-2009 Biology

• SAMADHAN KENDRA: A rural Information ENVIS is a decentralized system with a network of Technology Center for the benefit of rural distributed subject oriented centers ensuring integration population in West and East Godavari Districts of of national efforts in Environmental Information, Andhra Pradesh (sponsored by CSIR under Collection, Collation, Storage, Retrieval and RSWNET). Dissemination to all concerned. The SAMADHAN KENDRA is Rural Information The ENVIS networking system setup in different Technology centre for the benefit of community in rural organizations / establishments in India in selected areas areas. It is integrated internet-based, user-friendly of environment like pollution control, toxic chemicals, software. This has several built-in features like complete central and offshore ecology, environmentally sound and details about the agriculture i.e., Pest Disease appropriate technology, bio-degradation of wastes and Information System (PDIS) on the major crops of that environment management, etc. particular study area, types of control measures to be The EMCB ENVIS centre is to effectively bring out adapted etc., This also gives the information on seed various environmental management methodologies for management, quality, availability, fertilizer details like the control of vectors and vector borne diseases through procurement, application dosages, schedule etc. The integrated system and disseminate to various end users software also provide the details about Govt. schemes, like Post- Graduate Students of Environmental Sciences, subsidies and loan facility, list of Banks which offer Health Officials, NGOs etc. This is first of its kind to loans etc. for the benefit of the rural population. Farmers have a centre exclusively for information dissemination can down load the relevant application forms from the on Bioinformatics Vector Control and Vector Borne Samadhan Kendra. Public Health details like hospitals, Diseases. PHCs, availability of medicines were given to facilitate the local rural population. Success of any technology depends on the interest of end users. More than 75% population of this country belongs to rural areas, hence the IT application for the rural development has bright future in the coming Information era in the country like India. Samadhan Kendra is a Sustainable Rural Information Centre, which would be able to provide various IT, related services to the rural public and to concerned government departments.

ENVIS centre-home page

IICT Pursued the following activities in the ENVIS Centre ❖ Periodical up gradation of ENVIS home page with latest news on vectors and vector borne disease. ❖ Uploaded latest information on ìChandipur virus suspected in Andhra Pradesh, Chikungunya virus in West Bengal, out break of Chikungunya in Italyî. SAMADHAN KENDRA-Home page ❖ Developed a ìDengue Decision Support Systemî for • Environment management for the control of vectors identification of Dengue, Dengue Hemorrhagic Fever and vector borne diseases (Environmental (DHF) and Dengue Shock Syndrome (DSS). Information System (ENVIS) www.iictenvis.nic.in) ❖ Published ENVIS news letter and brochure focusing on (Sponsored by the Ministry of Environment and Dengue, Chikungunya at a glance and More about Forests (MoEF) Government of India) Dengueî.

Biennial Report 2007-2009 67 Biology

❖ Displayed ìENVIS-Bioinformatics Vector Controlî North East States of India (Assam and Manipur) activities at ìIX International Symposium on Vectors & (sponsored by CSIR under RSWNET). Vector Borne Diseasesî held at Puri, Orissa from The silkworm germplasm stock of IICT was screened 15.02.2008 to 17.02.2008. for BmNPV and high temperature using standard ❖ Conducted ìEvaluation workshop & training programme protocols. A few promising high yielding silkworm for the thematic ENVIS centers in Southern regionî varieties have been developed through conventional from 02.01.2008 to 05.01.2008. breeding methodology. IICT conducted 3 training • programmmes of duration of 2-3 days entitled sericulture An integrated information system for the control for the production of better cocoon crop for of bancroftian filariasis in Andhra Pradesh Implementation of new technology for rural development (Sponsored by Ministry of Communication & in sericulture at North East states of India (Assam and Information Technology, Govt. of India, New Delhi). Manipur) The main aim of the present study is to implementation • Advanced Course in Bioinformatics (Jointly of Datamining and GIS applications for the effective organized by IICT, CDAC and JNTU) control of filariasis in Andhra Pradesh. Entomological, Epidemiological and Socioeconomic data was collected In pursuit to strengthen the CSIR HRDG efforts to train form 120 villages from four districts, i.e., East Godavari, manpower to meet the challenges posed by the modern West Godavari, Karimnagar, and Chittoor were selected. day of science in 20th century, a program was designed The collected data was plotted on the GIS based model with collaboration with CDAC to start a ìAdvanced called Filariasis Monitoring Visualization System Diploma Course in Bioinformaticsî with a intake of 24 (FMVS). students (18 Open category 06 Sponsored) selected on the basis of ìAll India Common Entrance Testî, the The GIS based Filariasis Monitoring and Visualization course was designed for a period of 03 months including System (FMVS) will help the end user to quickly assess the project work and hands of experience for the course the intensity of the disease based on the information students. The response was quite encouraging not only provided by the visualization system. The health official from the studentís side but the academic giant JNTU; can take appropriate control measures in accordance Hyderabad also joined hands in this novel venture in to the intensity of the parameter displayed by the FMVS. the second year of the course inception. This will enable to initiate correct and efficient integrated control measures. The FMVS is easily operable and can be ported on all working platforms; this integration of data will be of immense help to the end user.

The course underwent a major change from the second year onwards the course period was increased from 03 months to 06 months duration and the title was changed as ìAdvanced Course in Bioinformaticsî as per then norms of the governing the universities. The present Main window displaying GIS mapping of the Karimnagar course for the year 2009-2010 is eighth batch in the district, Andhra Pradesh. series, the students of the earlier seven batches have been placed comfortably in the industries, universities, • Implementation of new technology and training academic and research intuitions, some of the program for rural development in sericulture at successful students have gone abroad to pursue their

68 Biennial Report 2007-2009 Biology

higher education in the field of Bioinformatics. As on • Toxicological evaluations and profiling date the Bioinformatics course jointly organized by IICT, ❖ Antirodent test was conducted as per SOP No. DOP/ CDAC and JNTU has carved niche for itself among the TOX/R-3 on four species of wild rodents i.e. Rattus aspiring students eager scale the horizons and rattus, Bandicota bengalensis, Tatera indica and challenges posed by science. Millardia meltada. Test reports were submitted to clients. • Toxicological studies of newly developed IICT attracted ten clients for these services. nanomaterials of medical importance using in • Feeding behaviour of castor semiloper vivo and in vitro model systems (Sponsored by The host location and feeding behavior of castor DBT, New Delhi) semilooper Achaea janata L. towards different castor The project was formulated in order to generate (Ricinus communis L.) plant varieties were studied. The toxicological data of nanomaterials of medical importance ovipositional preferences of adult moths and the feeding newly synthesized at IICT, Hyderabad. The behavior of the larval instars when exposed to leaf nanomaterials were Hydroxyapatite (HAP-10 & 20nm) surface chemicals as well as whole leaves were and Iron Oxide (Fe2O3ñ10 & 20nm). For comparison evaluated in the laboratory. Also the herbivore induced the bulk materials of HAP and Fe2O3 were used. The volatile chemical production in castor plants were studied acute oral and dermal toxicity of HAP & Fe2O3-10/ by extracting the leaf volatiles. The parasitoid attraction 20nm and their bulk materials have been conducted. to the plant volatile chemicals was measured using the The toxicity was greater than 2000 mg/kg. Our egg parasitoid, Trichogramma chilonis. To understand preliminary data indicate that the test compounds are the castor plant defense mechanism- the enzymatic not toxic. The genotoxicity of the test compounds was changes in the pest infested and normal castor leaves conducted by the MNT in bone marrow and comet was studied biochemically. assay in peripheral blood leucocytes in treated rats by • acute oral and dermal routes. HAP10/20 nm, its bulk Biopesticides from plant sources Many plants and plant parts were screened for their and Fe2O3 bulk were not genotoxic by MNT and comet efficiency against agricultural and stored product pests. assays. In comet assay by oral route, Fe2O3 ñ10/20 nm was genotoxic at1000 & 2000mg/kg and by dermal Three floral plants extracts have shown excellent activity. Active compound was isolated and identified by route at 2000 mg/kg in females only. In MNT Fe2O3 ñ10 nm revealed genotoxicity at 1000& 2000 mg/kg and at analytical techniques. Chemical characterization of leaf 2000mg/kg by oral and dermal routes respectively extracts of three plants also has been carried out and the active component was isolated. Antifeedant and whereas, Fe2O3 ñ20 nm showed genetic damage by oral route at 2000mg/kg. toxic activity of about 10 plant extracts was determined and the chemical isolation of active compound is under • Influence of plant chemicals and physical progress. These plant products will be used for the characteristics on insect behavior, host plant further development of biopesticides. Two plants were selection and oviposition in castor semilooper, highly promising and can be developed commercially. (Sponsored by DST). (Journal of Biopesticdes, 1 (1): 170-176, 2008, Journal The host location and feeding behavior of castor of Boipesticdes, 1 (1): 74-80, 2008, Uttar Pradesh semilooper Achaea janata L. towards different castor Journal of Zoology, Vol suppl I, pp 165-173, 2008, Journal (Ricinus communis L.) plant varieties were studied. The of Biopesticdes, 2, 72-76, 2009, J Agric. Food Chem. ovipositional preferences of adult moths and the feeding 57-6090:6094, 2009) behavior of the larval instars when exposed to leaf • surface chemicals as well as whole leaves were Discovery and Development of Pest Management evaluated in the laboratory. Also the herbivore induced Agents from Herbal Sources ñ (CSIR NWP-0037) volatile chemical production in castor plants were studied Institute of Himalayan Bioresource Technology (IHBT), by extracting the leaf volatiles. The parasitoid attraction Palampur is the Nodal Institute, and involves seven to the plant volatile chemicals was measured using the other CSIR Institutions as networking partners. These egg parasitoid, Trichogramma chilonis. To understand are: Central Building Research Institute (CBRI), the castor plant defense mechanism- the enzymatic Roorkee; Central Food Technological Research Institute changes in the pest infested and normal castor leaves (CFTRI), Mysore; Central Institute of Medicinal and was studied biochemically (Journal of Biopesticdes, 1 Aromatic Plants (CIMAP), Lucknow; Indian Institute of (1): 17-22, 2008, Allelopathy Journal, 24 (1), 2009, Chemical Technology (IICT), Hyderabad; National Management and Environmental Safety 4 (2): 69-76, Chemical Laboratory (NCL), Pune; National Institute of 2009, Communicated). Interdisciplinary Science and Technology (NIST),

Biennial Report 2007-2009 69 Biology

Trivandrum and North East Institute of Science and filter feeding activity. Hence, these are chosen as Technology (NEIST), Johrhat. The major objectives of biomonitors to reveal the status of the selected locations the project is to identify new molecular targets for the where they exist (Toxicological and Environmental discovery of plant derived insecticides and to share the Chemistry 2007, 89: 487-498; Environmental Monitoring sources to facilitate the discovery of novel bioactive Assessment 2009, 156:451-459). natural products that can serve as lead compounds for • Characterizing Collagen from Sponges development of new toxicologically safe environmentally benign pest management agents. The IICT Network Marine sponges of Gulf of Mannar have been extensively Project contributions are enumerated below: studied for the isolation, biochemical and biophysical characterization of filamentous, fibrillar and non-fibrillar ❖ A total of 6525 herbal extracts (methanol, methanol collagens. These collagens (purified fibrils as well as + water (1:1) and water) were screened against insect the TEM of irciniid filaments) have a typical band pests like Castor Semi-Looper, Achaea janata (2001- periodicity of 67nm, which is the characteristic feature 2005), Yellow fever mosquito, Aedes aegypti (2005- of vertebrate collagens (Ph.D. Thesis submitted to till date), and Diamond back moth, Plutella xylostella Osmania University). (2007-tilldate) for their larvicidal, pupicidal, anti- feedant and IGR properties. ❖ About 4516 samples were evaluated against A. janata, and very few of them (n=11) were found to be active as larvicidal, anti-feedant and IGR properties at 500 ppm level out of 308 extracts shown active at 1000 ppm. ❖ About 218 extracts out of 1603 shown larvicidal activity against A. aegypti at 400 ppm and 64 samples shown IGR properties at 1000 ppm on P. SEM image of isolated AFM image of purified xylostella. collagen filaments collagen fibrils ❖ Among them NCL-049 has multiple biological activities against all the test species particularly the extract possess larvicidal and IGR properties (active at 150 ppm against mosquito larvae, and 1000 ppm against Diamonds back moth, P. xylostella). • Marine Sponges as Biomonitors for Monitoring Metal Pollution in Gulf of Mannar Purified non-fibrillar TEM image of the ultrathin Gulf of Mannar (GoM) located in the south east coast collagenous sheets section of isolated filament of India, is the first marine biosphere reserve of India. The gulf is chain of 21 islands, with a coast line of • Marine Sponge Cell and Fragment Cultures 10,500 km , starting from Rameswaram to Tuticorin (8 Novel methods of in vitro marine sponge cell, fragment 45' N and 9 25' N and 78 05' E and 79 30' E). The and explant cultures are established to obtain Gulf of is known to harbor 3,600 species of flora and therapeutically significant molecules by regulating the fauna, making it one of the richest coastal regions in dissolved oxygen levels required for survival of sponges. Asia. The intense anthropogenic activity around the In the current scenario, sponge cell and fragment gulf during the recent past, causing a threat to biota, cultures are essential for faster growth of sponges, nevertheless, to assessing the metal pollution and to which produce potent molecules and biomaterials. study the environmental health status of GoM, the Survival rate of two demosponges, Axinella donnani and sessile invertebrates (marine sponges) could be used Haliclona pigmentifera were extensively studied under as biomonitors. in vitro conditions. Culture methods were developed to Marine sponges provide excellent features to be used enhance the in vitro adhesive growth of sponges (Cell as biomonitors for assessing metal pollution in coastal and Tissue Research 2009, 337:527-535) and also environment and are capable of accumulating high established the facility to maintain live sponges at concentration of metals for long periods, through their laboratory conditions.

70 Biennial Report 2007-2009 Biology

Marine aquarium Growth of sponges for 40 days

Sponge cells under culture

• Earthworm as Bioindicator for Monitoring Pesticide Pollution in Soils There is an increasing demand for newer experimental models that can be used as bioindicators for assessing the health status of terrestrial ecosystem. The earthworm toxicity testing is considered and highly recommended as bioindicators for assessing the chemical pollution in soils (European Communities, EC 2004). The bioefficacy and persistence of Profenofos (an organophosporous (OP) insecticide) in artificial soil was monitored using earthworm, Eisenia foetida as Altered gill architecture and bioaccumulation in different bioindicator (Ecotoxicology and Environmental Saftey tissues of fish, Gambusia affinis exposed to 20µg/L of 2008, 71: 574ñ582). mercuric chloride [a: Control, b: Day-8, c: Day-16, d: Day-20, • Effect of Mercury on Aquatic Organisms e: Day-24 and f: Day-28]. Elemental, inorganic and methylmercury are the three most important forms, which cause adverse effects on centrally along with the bait (caked and dried digested aquatic environment. It is known that methylmercury residue of herbivorous matter) in a bait station (earthen is highly toxic and accumulated in the tissues of fish, pot consisting a small hole at the bottom) and these which originates by the bacterial methylation of inorganic charged pots were fixed inversely at a location, after mercury. The pattern of bioaccumulation in various chopping an apical bud of active termite mounds and tissues of mosquito fish, Gambusia affinis exposed to allowed for termite infestation. The termite infestation sublethal concentrations was quantified and studied the was assessed by measuring the weight difference effects on behavioural, morphological, and between the initial and after exposure. histopathological parameters (Drug and chemical • Mode and Site of Action of Anti-Cancerous Toxicology 2007, 30:383-397). Molecules • Assessment of Termite Resistance Properties of Most of the anti cancers molecules are expensive and Optical Fiber Cables possess severe side effects. Hence, it is very important A novel methodology has been developed to assay the to determine the mode and site of action of the damage caused by the termites in actual field conditions molecules for effective treatment. During this process, (in short duration of 30 days) on commercially available cytotoxic potency and apoptotic mode of action of a optical fiber cables. The supplied running cable was molecule, Methyl 5-[(1E, 5E)-2,6-Dimethyl octa-1,5,7- cut into suitable lengths (3.5±0.5 inches) and placed trienyl] furan- 3-carboxylate (MDTFC) isolated from a

Biennial Report 2007-2009 71 Biology

A) Supplied/Test running cable. B) Cut pieces of cable sample (3.5±0.5 inches). C) Identification of active termite mounds (brake opens the apical bud and found termite casts present in the mound). D) Bait stations along with test samples (charged pots), fixed inversely at active termite mounds under ambient natural outdoor conditions for a period of 30 days (Field-Test). E) Detached the bait station from active termite mound after exposure tenure (presence of termites are visible on the surface of bait station). F & G) Break open the bait station and removal of test cable samples). H) Visual observation of test cable samples, and I) Evaluation of test samples under magnification to find feeding marks on the surface.

soft coral, Sinularia kavarittiensis were elucidated on

Thp-1 leukemia cells (IC50 7.67µg/ml). The molecular mechanism of MDTFC mediated apoptosis involves decrease in level of pro-caspases 3, 9, increase in Bax/Bcl-2 ratio, cleavage of poly (ADP- ribose) polymerase, chromatin condensation and DNA fragmentation. Flow cytometric analysis revealed a sub- G1 peak and a reduction in mitochondrial membrane ψ potential ( m). All these results indicate that a mitochondrial-dependent pathway exists in MDTFC mediated apoptosis and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells (Apoptosis 2009, 14:729ñ740). Similarly we have also been actively involved in screening of novel synthetic compounds (Indian Journal of chemistry, 2009, 48B, Representative plots of cell cycle arrest (sub-G1 840-847), their derivatives and decipher their apoptotic hypodiploid population) with PI staining in Thp-1 pathways on various cancerous cells. leukemia cells treated with MDTFC.

72 Biennial Report 2007-2009

The Pharmacology division caters to the need of in house ❖ Influence of Ayush Manas on Episodic Memory in rats. R&D divisions and pharmaceutical industries. It is actively ❖ Acute and sub acute toxicity study or Ropivaciane involved in R&D activities related to pharmacological hydrochloride injection (Formulation) in rats and mice. screening, Novel Drug Delivery Systems for various drugs. The projects include formulation, pharmacokinetic and ❖ Chronic toxicity study and subacute toxicity study of pharmacodynamic evaluation. ayurvedic bhasma ëeí in rats and mice. Some of the R&D projects undertaken are: ❖ Sub acute toxicity study of ayurvedic bhasma ëeí in rats and mice. ❖ Pharmacological screening of various new chemical entities in the areas of inflammation, arthritis, diabetes ❖ Evaluation of immunomodulatory activity of Ayush and cancer by following novel tools of drug discovery of Formulations. drug formulations. ❖ Evaluation of the In vivo efficacy of PEG-GCSF and Pharmacological Screening Services Provided to GCSF by Cyclophosphamide (CPA) induced Neutropenia Pharma Industry: in mice. ❖ Study of controlled release pharmaceuticals from ❖ To evaluate the aphrodisiac activity of safed musli proprietary biomedical devices. (Chlorophytum borivilianum) in adult Wistar rats. ❖ Acute and chronic toxicity study of chymosin in rats ❖ Acute toxicity study of Fosphenytoin Sodium and rabbits. (Formulation) administered intravenously in rats and ❖ Dose escalation and tissue distribution studies of mice. Monoisoamyl Dimercaptosuccinic acid after oral ❖ Sub acute toxicity study of wound healing peptide administration in rats. (GENOPEP) in rats and rabbits. ❖ Acute and sub-acute toxicity study of Ropivacaine ❖ Anti-inflammatory activity of drug compounds by Hydrochloride Injection (Formulation) in rats and mice. carragennan induced Rat Paw Edema model. ❖ Acute oral toxicity study of proprietary ayurvedic ❖ Acute oral toxicity study of SMSRC ñ 0401. medicine in mice and rats.

Biennial Report 2007-2009 73 Chemical Engineering Sciences

Chemical Engineering Sciences is one of the major divisions Alkalies and Chemicals Ltd., for the development of of IICT involved in development of technology for industrially internationally competitive technology for Hydrazine important products, besides carrying out the basic research Hydrate. This product is extensively used in space in frontier areas of chemical engineering. The following are applications, fuel cells, intermediate in drugs and the major areas of activities of Chemical Engineering agrochemicals industry and blowing agent in polymers Division: Process Development, Process Design, Process industries. This process based on hydrogen peroxide Safety (PROSAC), Process Modeling and Simulation, route is environmentally benign. Bench scale Dynamics and Control, Reaction Engineering, Membrane experiments of capacity 100 gr/hr are being carried out Separations and Properties Measurement and Evaluation. to develop the continuous process and also to generate data for design of pilot plant of 12 kg/hr capacity and APPLIED RESEARCHRESEARCHAPPLIED subsequently to design a commercial plant of 8000 The thrust areas of applied research are: i) Process tonns/annum capacity. The plant will be erected by development & design, ii) Process dynamics & control, iii) GACL at Dahej, Surath, Gujarath and is expected to Process safety and iv) Membrane separation. be in operation in the middle of 2011. ••• PROCESS DEVELOPMENT AND DESIGN Recovery of Dimethysulfoxide (DMSO) solvent from pharmaceutical effluent. (Sponsored by Astrix Process development and design for commercialization of Laboratories Ltd., Kazipally, Medak, A.P.) technologies is one of the major activities. The objective is primarily to develop the eco-friendly process technologies A hybrid process involving electrodialysis and distillation for chemicals belonging to the agrochemicals, speciality was developed for recovery of DMSO solvent from an chemicals and petrochemicals sectors, chosen on aqueous solution of DMSO containing hazardous the basis of demand and/or engineering challenges. The design sodium azide and ammonium chloride salts. In this of commercial plants involves scale up studies, process, first the sodium azide and ammonium chloride design data generation, design and commissioning of salts are removed from the effluent by electrodialysis plants and providing the guaranty runs to clients. Software and the resulting salt free DMSO-Water mixture are packages like CAD as well as the software developed separated by distillation. The process was demonstrated in-house are extensivelyused for synthesis of process successfully to the client and a basic design report for flow sheets, equipment specifications, plant layout a commercial plant to process 7500 liters/batch/day of drawings, P&I diagrams, pipelinerouting diagrams and single the effluent was prepared and submitted to the client. line electrical diagrams andrelated items. The commercial plant is installed and the commissioning of the plant is in progress.

••• Synthetic Aviation Lubricants (Collaborative Project) A consortium consisting of IICT, IOC-R&D, NAL, HAL, GTRE and CEMILAC formed with IICT as the nodal agency to develop indigenous technology for aviation lubricants. Process Know-how for the preparation of the base oils SVS1 and SVS2 from renewable feed stocks has been developed and a pilot plant of a capacity of 100 kg/batch has been designed. The base oils were found to match with the international specifications of 9DEFSTAN 91-101/5 and MILPRF- 23699F. About 500kg of SVS-11 base oil was prepared on pilot plant and sent to IOC R&D for evaluation, formulation and processing. The lubricants prepared using these base oils were successfully tested at NAL for bearing test and at HAL for Engine test. About 120 Kg of SVS21 was also prepared on pilot plant and sent to IOC R&D for evaluation and testing. Electrodialysis Pilot Plant for sodium azide removal for DMSO recovery from pharmaceutical effluent ••• Hydrazine Hydrate (Sponsored by GACL, Baroda, Gujarat) REACTION CALORIMETER (RC) IICT had entered into an agreement with M/s. Gujarat Reaction Calorimeter is used to study thermokinetic

74 Biennial Report 2007-2009 Chemical Engineering Sciences behavior and to assess the potential hazardous nature the Hyderabad, EPTRI, Hyderabad, M/s. Bharat Petroleum reactions/individual steps of the reaction nearer to the Corporation Ltd., Cherlapally, A.P., M/s BHPV, conditions prevailing in industry. The clients include M/s Vishakhapatnam and M/s. Bhagiradha Chemicals & Matrix Labs., Hyderabad; M/s HEMRL, Pune; M/s SANDOZ, Industries., Ongole. Thane and M/s Neuland., Hyderabad. Commercial Software Acquired ACCELERATING RATE CALORIMETER (ARC) • PHAST/SAFETI-Micro Accelerating Rate Calorimeter studies for the reaction Developed by DNV Technica, London to provide mixtures were conducted to assess the potential runaway comprehensive chemical process hazard analysis. behaviour and to get a complete understanding of the Upgraded to version 6.53 hazardous nature of individual process streams for M/s Matrix Labs., Hyderabad and M/s NOCIL India, Mumbai. • PHA works 5.01 is a powerful Process Hazard Analysis tool for conducting HAZOP, What If, FMEA, DIFFERENTIAL SCANNING CALORIMETER (DSC) Checklist, RMP Hazard Review and RMP Standards The Differential Scanning Calorimeter (DSC) is highly Review. sophisticated and more precise in measuring thermal ❖ Consequence of release of toxic substance (H S) properties such as phase transition, heat capacity, 2 isothermal curing, glass transition and reaction kinetics, in offshore platforms. (Sponsored by IEOT(ONGC), etc. The instrument is functioning under ISO 9001:2000 Mumbai.) and quality service is offered to various commercial firms Aim of the project is to develop a customized software and research scholars from different universities. for dispersion studies of dense toxic gases like H2S for ONGC offshore platforms in order to determine the ❖ Optimal Operation and Advanced Control of concentration of H S gas at various locations away Reactive Batch Distillation Processes (DST 2 from the source of leak. Sponsored Project) A multi-purpose distillation unit with instrumentation and The main features of the software developed ëDISTOXí data acquisition and control software are installed and are: tested. Experiments are conducted for kinetic model • For a given temperature, pressure and area of leak development and also for dynamic model development. of the sources like vessels, pipelines, columns etc., CHEMICAL PROCESS SAFETY ANALYSIS the software would estimate the leak rate and also the concentration of H S at various distances from The Process Safety Centre (PROSAC) was established in 2 the source of leak for a given atmospheric conditions the year 1988 and over the years developed expertise in like temperature, wind velocity etc. the areas of Hazard Analysis & Risk Assessment, Safety Audit, HAZOP and Disaster Management Studies. • It takes into account of both instantaneous and PROSAC offers its expertise and services to various continuous mode of gas release and also the effect chemical, petrochemical and agrochemical industries. The of obstacles on dense gas dispersion. chemical plant industrial activities associated with • Necessary graphical user interface has been processing, storage and transportation of hazardous developed and incorporated into the software to guide chemicals where fire, explosion and toxic hazards that are the user to input necessary data for the software likely to take place and reasonable risk to society exits and also to analyze the output results. are studies in detail. • Copyright has been obtained for the software. Process Safety Centre successfully completed ❖ approximately 14 Hazard Analysis and Risk Assessment, Cost Estimation and Feasibility for the Reports Safety Audit, Hazop and Onsite and Off site Emergency The development of a design project proceeds in a plans and Disaster Management assignments during this logical, organized sequence requiring time, effort and period. In addition, samples of various chemicals were expenditure as one phase leads into the next. It is analyzed for the hazardous properties, such as flammability/ extremely important, therefore, to stop and analyze the explosive limits, auto ignition temperatures and situation carefully before proceeding with each overpressure waves generated when explosion takes place. subsequent phase. If the engineer's work is continued Some of our clients for whom these studies were carried through the various phases of a design project, it out are M/s. Astrix Laboratories Ltd., Kazipally, Medak, eventually ends up in a proposal for money to be A.P., M/s L&T Ramboll Consulting Engineers Ltd., invested in the process. Therefore, the engineer should Hyderabad, Central Bureau of Investigation , Govt. of India, have the ability to eliminate unprofitable ventures before

Biennial Report 2007-2009 75 Chemical Engineering Sciences

the design project approaches a final proposal stage. and PLC is from Rockwell software. Extensive The procedures for cost estimation and feasibility reports experimental work is carried out to collect the data on of chemical industries w.r.t. Indian scenario are two phase pressure drop, liquid holdup and interfacial established based on the standards IS : 8010 (Part II) - area. Separate correlations were developed to predict 1982. The reports can be generated at three stages: these parameters in terms of system and operating 1. When only preliminary information is known about variables. Further studies include the measurement of the process. 2. If the basic data for scale up is available other hydrodynamic parameters such as RTD, mass and 3. When designs for commercial plants are transfer coefficients at atmospheric as well as at high complete. The main contents of the reports include pressures. fixed capital investment, working capital investment and ❖ Bubble column reactor economic analysis of the plant. Bubble column reactor is a device in which gas phase BASIC RESEARCH is bubbled through a column of liquid to promote a chemical or biochemical reaction in the presence or The chemical engineering division undertakes the basic absence of catalyst. A state of art bubble column reactor studies in kinetics of industrially important processes, setup has been fabricated and erected by Xytel India. equipment development needed for scaling up and process This unit consists of a SS 316L column and a Perspex optimization, process dynamics and control. The result column of internal diameter of 0.106 m, height of1.5 m. obtained from these studies are published in form of It is provided with sophisticated instruments to measure research papers in reputed journals. the pressure, temperature and conductivity, which can ❖ Modeling of a Reactive Batch Distillation Process be monitored and controlled by PC/PLC/SCADA Using Time-Varying Neural Networks system. The reactor can be operated under a pressure 2 0 Simulation studies are conducted for literature reported of 10Kg/cm and temperature up to 200 C. Experiments system, and a time-varying neural network model is are being carried out to measure the hydrodynamics developed and validated. [International Conference on and heat and mass transfer parameters using the Advances in Manufacturing Technology for Young industrially important systems such as Glycerol, CMC, Engineers, ICAMT2008] Starch, Pulp and Lubricant. The effect air flow rate, type of distributor and properties of the fluids on ❖ Optimal Operation of a Reactive Batch Distillation dispersion coefficient and heat transfer coefficient are Process using Control Vector Parameterization evaluated. Optimization problem is also formulated and solved for ❖ Studies in an Agitated Vessel a reactive batch distillation process. [International Studies carried out on the flow pattern and heat transfer Conference on Advances in Manufacturing Technology phenomena in an agitated vessel using the industrially for Young Engineers, ICAMT2008] important fluids such as Castor oil, CME, CMC, Starch, Pulp and Chalk slurries. Tracer studies are performed ❖ ❖ Hydrodynamics of gas liquid up flow through to characterize the flow pattern and the data is analyzed packed bed by single and multi parameter models. Correlations are Packed bed reactors are extensively used for the transfer developed between the model parameters and the of mass and energy in chemical process industries. operating variables and applied for scale-up of a Some of the important industrial applications include commercial reactor. [Paper accepted for publication in hydrogenation, hydro desulphurization and chlorination. Chemical Engineering Research and Design, 2009] Proper design and modeling of the reactor requires the ❖ Liquid-liquid extraction modeling knowledge to predict the various hydrodynamic A novel, semi-analytic and numerically convenient parameters such as two phase pressure drop, interfacial algorithm has been proposed for predicting the area etc. A computer controlled packed bed reactor equilibrium tie-line composition with given overall feed with internal diameter of 100 mm and height of 1000 composition and binary interaction parameters of mm is set up to generate the data on various established models (UNIQUAC and modified UNIQUAC) hydrodynamic parameters. The unit consists of flow for ternary liquid-liquid systems. The merit of the controllers, pressure indicators, conductivity probes and proposed model rests on the selection of distribution solenoid valves with communication ports. Total coefficient of each component as unknown variables operation of control, data acquisition, and data storage instead of the mole fraction. Moreover, the model relies and safety management is done automatically by the on the analytical solution of the extract fraction instead PLC/SCADA system. Communication software for PC

76 Biennial Report 2007-2009 Chemical Engineering Sciences

of adopting any numerical schemes that are commonly separations give excellent yields of very high purity and practised to solve the same. Its veracity has been also high degree of separations. Higher temperatures successfully tested with the experimental results for though, are detrimental in some cases, as in the standard ternary systems reported in literature. The extraction of specific compound(s) from natural matter calculation procedure renders a distinct advantage over that is generally thermally labile. Research has been the accepted existing methods from the utilitarian view underway for developing new EOS, mixing rules, point.[ìDevelopment of a Simple Model for the Prediction modified the existing equations and mixing rules by of Tie- Lines for Ternary Systemsî ,Accepted for defining new parameters for accurately predicting VLE publication in ìSeparation Science & Technology]. data at higher pressures for the systems of interest. But most of the methods employed have been found to The solubility and tie-line data of the ternary system be short of good predictions for HPVLE. We are comprising water, formic acid and methyl isobutyl ketone attempting to carry out HPVLE measurement for single were experimentally determined at the temperatures component, binary, ternary and multi ñ phase systems 288.15, 298.15 and 308.15 K, and atmospheric pressure belonging to Oil, natural gas & petroleum, petrochemical 101.3 kPa. The plait points were also determined using industry products, natural products, food, cosmetic & Treybalís method. The results indicate that formic acid nutraceutical industry and pharmaceutical industry. distributes preferentially in MIBK than in water. Experimental tie-line data was regressed with NRTL ❖ Study on design parameters for bio-diesel reactor model to obtain binary interaction parameters. It is found There are many processes available for making that the NRTL model correlates the present system biodiesel. Most of the technologies can be adopted satisfactorily with average root-mean-square deviation under different conditions for varying feedstocks. The of 0.34%. [ìSolubility and Tie-line data for Water+Formic technology choice is a function of desired capacity, Acid+Methyl Isobutyl Ketone Ternary System at feedstock type, quality, alcohol recovery and catalyst Different Temperaturesî, accepted for publication in recovery. Transesterification is the most common Chemical Engineering Communications] method used to get biodiesel. The transesterification is ❖ Recovery of chlorine from aqueous hydrogen carried out using a base catalyst where the ester chloride conversions of 96-98% are achieved easily. As glycerol Aqueous hydrochloric acid (HCl) is a by-product is the byproduct obtained during biodiesel processing frequently generated by chemical and pharmaceutical to make the biodiesel process more economical industries. It is a by-product of many manufacturing research is being carried out to convert the glycerol to processes that uses chlorine as a reactant. Most often acetal insitu to enhance some of the properties of some or all chlorine used is reduced to hydrogen biodiesel. chloride, a waste by-product. Hydrogen chloride is sold ❖ Reactive extraction of pure glycerol from aqueous as aqueous HCl or used as a raw material for the solutions via reversible reactions. production of chlorinated products, but the quantity of Conventionally recovery of glycerol from aqueous HCl produced by chlorine processes is much more solutions is usually achieved in multiple effect than what the market can absorb, resulting in a toxic evaporators or distillation. The heat required per kg of waste disposal problem. Electrochemically, HCl can be recovered material is high and the purification steps directly converted to chlorine and hydrogen. Compared increase with increase in impurity levels. Different to oxidation processes, electrolysis is a low temperature methodologies for achieving pure glycerol other than operation and the amount of water associated with the the conventional approach may prove to be more energy electrochemically produced chlorine is lower. Also the efficient. An alternate easier recovery approach is by co-produced hydrogen has commercial value. The only reactive extraction. Research is therefore focused mainly available commercial process was Uhde process. on recovery of glycerol from aqueous streams by Research is being carried out to treat aqueous HCl to reversible reactions. The process utilizes an acid produce Cl using an electrolyzer with anionic 2 catalyzed condensation reaction of glycerol with membrane equivalent to that of NAFION. Initial aldehydes and ketones to form acetals. The acetal is experiments and optimization stuides have been hydrolyzed to recover the glycerol in its purest form. extremely encouraging. Further research is therefore being carried out. ❖ Delignification of Bio-mass ❖ High pressure VLE Lignocellulosic feedstock are composed primarily of High pressure vapour-liquid equilibrium has a wide field cellulose, hemicellulose and lignin. Lower concentrations of application. High pressure and high temperature of various other compounds, such as proteins, acids,

Biennial Report 2007-2009 77 Chemical Engineering Sciences

salts, and minerals are also present. Cellulose and networks are presented for modeling and optimization hemicellulose, typically make up two-thirds of cell wall of pharmaceutical formulations involving several dry matter (dry matter: the portion of biomass that is competing objectives [Proceedings, International not water), are polysaccharides that can be hydrolyzed Conference on Modeling and Simulation (CITICOMS to sugars and then fermented to ethanol. Lignin plays 2007), Coimbatore, 27-29, August 2007; International the role of giving strength and protection to the feedstock Journal of Neural Systems, 2009 (In Press)]. and hence it has to be removed to enable the use of ❖ Artificial Neural Networks for Identification of Gene lignocellulosic feedstock for fermentation. Lignin cannot Sequences be used in fermentation processes. Delignification of the three feedstocks of corn cobs, sweet sorghum An artificial neural methodology is presented for bagasse and cotton stalks were carried out. classification and identification of Anopheles mosquito Delignification has been carried out using solvents and species based on the internal transcribed spacer 2 alkaline hydrogen peroxide. About 95% of delignification (ITS2) data of ribosomal DNA string. The results has been achieved. IICT has developed both chemical demonstrate the efficiency of the neural network method and enzymatic routes for the conversion of biomass to to extract the genetic information in ITS2 sequences xylose and xylitol. and to adapt to new data [Computational Biology and Chemistry, 32, 442-447(2008) ; Nature India, Doi ❖ ❖ Model Predictive Control of Reactive Distillation : 10. 1038/nindia.2008.334]. Reactive distillation (RD), the process of performing ❖ Nonlinear Fault Diagnosis of Chemical Processes chemical reaction and multistage distillation Using Data Driven Multivariate Statistical Models simultaneously has emerged as a favorable alternative to conventional reactor-separator configurations. Model Monitoring and diagnosis of process operations is predictive control (MPC) is an important branch of gaining importance to ensure process safety and to automatic control theory with wide industrial enhance process efficiency and productivity. The task applications. Multistep linear model predictive controllers of fault diagnosis is to identify an assignable cause of and nonlinear model predictive controllers based on out-of-control status of the process in order to take stochastic optimization are presented for the control of corrective actions to bring the process back to its normal highly nonlinear multivariable distillation processes status. Kernel space methods such as scatter- [Industrial & Engineering Chemistry Research,47, 6949- difference-based discriminant analysis (KSDA) and 6960(2007); Indian Journal of Chemical Technology, 14, dynamic kernel scatter-difference-based discriminant 330-340(2007)]. analysis (DKSDA) are presented for fault diagnosis of highly nonlinear processes. ❖ Development of Soft Sensors for Inferential ❖ Estimation of Compositions in Distillation and Soft Sensor Based Nonlinear Control of a Chaotic Reactive Distillation Reactor Optimal sensor configuration and estimation of Control of nonlinear systems exhibiting complex unmeasured process variables has become highly dynamic behavior is a challenging task because such significant in plant operations from on-line monitoring systems present a variety of behavioral patterns and control point of view. Various soft sensors based depending on the values of physical parameters and on dynamic process models as well as artificial neural intrinsic features. A soft sensor based nonlinear controller network models have been developed for compositions strategy is presented and applied to control a chemical estimation in multicomponent distillation and reactive reactor that exhibit multi-stationary unstable behavior, distillation processes [Journal of Scientific & Industrial oscillations and chaos. [2nd IFAC International research, 66, 898-904(2007); Proceedings, 60 th IIChE Conference, September 21-23, 2009, Instambul, Turkey Diamond Jubilee Conference, Kolkata, Dec. 2007 ; (accepted)] Journal of Process Control, 2009 (In Press)] ❖ Data-Driven Model Based Control of a Multi-Product ❖ Modeling and Optimization of Pharmaceutical Semi-Batch Polymerization Reactor Formulations An Artificial Neural Network based Generic model Control A Pharmaceutical formulation is composed of several (ANNGMC) approach is proposed for semi-batch formulation factors and process variables. Efficient processes with relative order higher than one, and its modeling and optimization techniques are needed to performance is illustrated by applying it to a a multi- devise an optimal formulation system. Methods based product semi-batch polymerization reactor challenge on artificial neural networks and radial basis function problem. [Transactions IChemE, Part A, Chemical

78 Biennial Report 2007-2009 Chemical Engineering Sciences

Engineering Research & Design (International) Journal, 85 (A10) 1397-1406, (2007)] ❖ Batch Process Modeling using explicitly Time- dependent Neural Networks A novel neural network structure incorporating time- dependency explicitly is proposed to represent the dynamics of batch processes and its capability is illustrated by employing it to represent the dynamics of a batch reactor accurately. [CHEMCON 2007] ❖ Optimal Control of a Fed-Batch Fermenter Using Data-Driven Models An optimal control approach is proposed for semi-batch processes based on parameterized data-driven (PDD) model structures including two new model structures, Gas Separation Pilot Plant commissioned at ONGC-Hazira and is shown to be capable of capturing nonlinear and based on Membrane Developed by IICT time-varying behavior inherent in fed-batch systems fairly accurately and resulted in good operating trajectory optimization results. [Journal of Scientific & Industrial Research, 67 (10) 759-773, (2008)] ❖ Process Intensification by Reactive Separations Some of the reactive absorption, reactive extraction / stripping, membrane-based reactive separations, reactive adsorption, and reactive crystallization are reviewed with the help of some examples, along with the potential benefits and limitations, and possible applications. [Chemical Industry Digest, XXI (3) 78-87 (2008)] MEMBRANE SEPARATION PROCESSES The major activity here is the development of suitable membranes for specific industrial separation problems Defluoridation Plant of 1000 L/h Capacity at Allapur Village, followed by studies on a bench scale and upscaling to a Nalgonda District pilot plant/commercial scale. Alternately, identification of suitable commercially available membranes is also Village, Nalgonda District for reduction of fluoride undertaken for development of separation processes for concentration from 2.3 ppm to < 0.25 ppm at a recovery different applications. Other activities include publications, of 50 %. patents, rural welfare projects, human resources development (student training) and laboratory development. iii) IICT-Academia Collaboration (Sponsored by Karnatak University) TECHNOLOGY TRANSFER IICT conceived, designed and installed membrane i) Commissioning of gas separation pilot plant laboratory at Karnataka University Dharwad for M.Sc (Collaborative projects) and Ph.D. students 3 Commissioned gas separation pilot plant of 94.4 NM /h Laboratory Development Network project scheme capacity in 2007 for sweetening of natural gas at Oil (NWP - 0047) and Natural Gas Corporation (ONGC), Hazira in collaboration with Engineers India Limited (EIL), Gurgoan. IICT has successfully designed and commissioned a manual spinning machine for preparation of hollow fiber ii) Installation of Defluoridation Plants in Affected membranes which offer high surface area per unit volume. Areas of Andhra Pradesh (Sponsored by DST These membranes find application in disinfection of surface Project) water for drinking purpose by ultrafiltration (UF) technique. • First RO Plant of 1000 L/h capacity installed at Allapur The fibers can also be modified through coating methods

Biennial Report 2007-2009 79 Chemical Engineering Sciences for other applications like nanofiltration and pervaporation. Hollow fiber membranes of polyethersulfone (PES) polymer were successfully prepared at IICT laboratory.

Manual hollow fiber spinning machine at IICT Membrane Laboratory

Gas Saperation

Pervaporation Electrodialysis

Gas separation, Electrodialysis and Pervaporation systems installed by IICT at Karnataka University, Dharwad

80 Biennial Report 2007-2009 Mechanical Design & Engineering

APPLIED RESEARCH UDA and Heptaldehyde as major products and designs for Pyrolysis Section (200 kg/hr of CME). • Detailed Engineering Design of Pilot Plants ❖ Hydrazine Hydrate Technology Sponsored by ❖ Setting up of a Pilot and Testing Facility for GACL, Baroda - Designs for hydrazine hydrate bench Preparing and Testing of Physicochemical scale facility (100gm/hr), Pilot Plant (12kg/hr) & 8000TPA Properties of Base Stock of Lubricants for Aviation commercial plant to be carried out under the Industry - Detailed Engineering inclusive of mechanical assignment. Work is in progress. design of equipments, layouts and elevations, & piping ❖ engineering was completed; Pilot plant erection and Preparation of Tender Document for Detoxification mechanical commissioning was also completed; Pilot / Decommissioning / Dismantling of UCIL Plant, Plant is in operation. Bhopal (Sponsored by Ministry of Chemicals & fertilizers & Govt. of MP) - Work includes preparation ❖ Setting up of a Biotechnoilogy Incubation Centre of equipment layouts, calculation of equipment loads; at SP Biotech Park, jointly with Andhra Pradesh piping plans & isometrics; estimation of quantity of State Government ñ Being the state of the art facility contents to be detoxified; procedure for dismantling of for incubating biotechnologies and to provide world-class equipment and piping, etc. Work is in progress. facilities to different clients for scale-up of their ❖ Detailed designs of Distillation Systems were provided processes, work continued in full flow during the reporting to Kekule Pharma Limited, Hyderabad. period. Construction of laboratories and pilot plants is completed. Commissioning of various facilities/systems ❖ Basic Designs for recovery of DMSO solvent from like fermentation, downstream processing is in progress. effluents for Astrix Labs Limited, Hyderabad were BTIC will be operational by the end of December, 2009. provided. • ❖ Setting up of a Pilot Plant for Standardization of SAFETY ASSIGNMENTS UNDERTAKEN WITH Biodiesel Process - Mechanical design of equipment, PROSAC preparation of tender documents and project ❖ Determination of Emergency Venting Requirements of management was completed and engineering activities storages, reactors, etc for Astrix Labs Private Limited, at the time of erection and commissioning of the plant Hyderabad were prepared. were taken care of. The pilot plant is ready for process ❖ Process safety audit studies were carried out for trials. Rayalseema Alkalis and Allied Chemicals Plant • Detailed Engineering Design of Commercial Plants: Complex, Kurnool. ❖ Designs of Pyrolysis Section sponsored by M/s ❖ Risk analysis & safety review of LPG bottling plant, for Jayant Oil Mills (P) Limited, Vadodara. Mechanical BPCL, Cherlapally. design and development of detailed drawings of the ❖ Risk analysis studies of Vemagiri Power Plant, pyrolyzer and other upstream and downstream Rajahmundry. equipments with plant layouts, process and utility piping ❖ specifications were prepared for providing the technology HAZOP studies of high-pressure boiler system, of BHPV, package, to sponsor. This includes process know-how Visakhapatnam. for pyrolysis of Castor oil methyl esters (CME) for the ❖ Risk assessment studies of Bhagiratha Chemicals & preparation of crude pyrolysed product containing Methyl Industries, Ltd, Ongole.

Biennial Report 2007-2009 81 Computer Centre

The IICT Computer Centre undertakes applications of administration, email administration, client/server software development in the areas of scientific importance administration, OS and application software installations to institutional programmes, besides providing scientific and trouble shooting, server administration, etc. inputs based on computer aided techniques to R&D ❖ Network administration across multiple platforms and projects and conducting training programes in advanced under various environments utilizing the state of art computer programming. It also provides services in technologies networking, troubleshooting, guiding users in hardware ❖ User guidance in identifying their IT infrastructure and software installations, etc. requirements and the technologies. CSIR ICT PROJECT Campuswide Networking ñ New Network Connections This is a prestigious project of CSIR and CSIR has ❖ allocated rs.1.3 crores for this project. Various activities of Wifi connectivity was provided in the Committee Room, this project have been executed successfully during period New Lecture Hall and the two Guest Houses under report. The main activities of this project include ❖ Network connectivity was provided in the NPL revamping of the entire IICT campus wide network with the Extension building, 2nd floor(15 nodes), and also in the latest state of art technology. This includes various activities Evolva building(40 nodes) like procuring the active and passive network components, ❖ Provided the network and other services to the servers, software and other necessary accessories, conferences conducted at IICT installing all the equipment, testing the new infrastructure ❖ Provided network connectivity to 35 nodes in different and finally implementation of the new infrastructure. This rooms of the first and second floors of the new RFID project is successfully completed and the new network, security building. hardware, software, servers, etc. are put to use for the ❖ Network and other services to the international campus wide networking services. conference ASOMPS, conducted at IICT during the Installation of Video Conferencing(VC) Studio Facility period Nov. 2-4,2008. at IICT Software Development and Maintenance Activity CSIR has provided the VC equipment to all the labs as a ❖ Software was developed for the pathology section of part of ICT project. The project is actively supervised and IICT/CCMB dispensary, which is developed in VB6 and the installation of the video conferencing studio in the MSACCESS. This software generates various Directorís Annexe room by associating with the officials of pathological reports like urine analysis, blood sugar M/s SPANCO Telesystems(Supplier) is successfully levels(fasting and post lunch), hematology, analysis of completed. The video conferencing studio is now installed thyroid testing, biochemistry profile, lipid profile, at IICT and the facility was successfully tested by holding pathology analysis, etc. video conferencing with CSIR Hqrs., CMMACS, NGRI, ❖ Spanco office, etc. A demonstration was arranged to Maintenance of intranet sites : http://cafas, http://ccnet Director, IICT. Thorough practical training was imparted to ❖ Monitoring of various log files of the database and other the IICT computer centre staff. Using this facility, it is now servers possible to hold video conference with four other sites/ ❖ Maintenance of windows update server, antivirus server labs. etc. Troubleshooting and Inhouse Maintenance of the ❖ Under the ICT project, ChemBioDraw Ultra 11.0 software Network was procured, which is very useful to chemists and This is an ongoing activity of the computer centre and biologist. This software was successfully installed for various tasks related to this activity are listed below: nearly 25 scientists, who are finding it very useful in their day to day work. ❖ Inhouse maintenance of over 800 desktop machines and over 20 servers Education and Training Activities ❖ Providing network services like internet, email, network ❖ Helping various users in successfully conducting connectivity and trouble shooting, wify connectivity, etc. various training programes related to computer software, ❖ Network monitoring and internet usage by tools like network, mathematical and statistical modeling. sniffer, MRTG, squidlog reports, etc. ❖ Helping the Examination Branch, Osmania University ❖ Providing new email and internet accounts to the users for the paper setting and in conducting practical ❖ Attending to various administration tasks like database examinations for the M.Sc.(Statistics) course.

82 Biennial Report 2007-2009 Bioengineering And Environmental Centre

RENEWABLE ENERGY FROM WASTE of de-oiled cake per day. Extensive bench scale DESIGN AND DEVELOPMENT OF HIGH RATE experimentation and collection of engineering data DIGESTORS required for the design of a new variant pilot scale high rate digester and identifying operational difficulties during • Design and development of prefabricated high the process are the major objectives of the second rate digester for rapid biogas production stage of the project. In this regard customized design (Sponsored by MNRE, New Delhi) of two-bench scale digesters was made and the scheme The Major objective of the project is to design a of the proposed bench scale digesters is given below prefabricated high rate digester suitable for semi-urban (Figures 1 & 2). and urban areas for disposal of kitchen waste. Volume of this compact digester will be 1.5 m3 and it is designed MICROBIAL FUEL CELL (MFC) suitably for high treatment efficiency in terms of • Bioelectricity from wastewater treatment: percentage solids reduction, operational convenience, Microbial fuel cells with variable configurations (single aesthetic look and affordable cost similar to a fully and dual) using non-catalyzed graphite as electrode automatic washing machine. The unit will be suitable and anaerobic mixed consortia as anodic biocatalyst for treating leafy, powdery, fibrous or dry biomass waste were evaluated for power generation potential employing from kitchens and garden and produce biogas for direct chemical wastewater, pharmaceutical wastewater, consumption. The proposed digester will be able to distillery based wastewater, diary based wastewater treat approximately 50 kg of waste (60% moisture) and domestic sewage as substrate (Fig 3 & 4). The daily and produce 2 to 3 m3 biogas. Various design fuel cells showed to generate power and degrade the configurations for the digester tank or vessel were made. substrate, but the performance was found to depend on A 500 lit. capacity digester was fabricated and the nature of substrate used, MFC configuration and preliminary trials were conducted. Preliminary trials were operating conditions (Fuel 87 (2008) 2667ñ2676; conducted to obtain data for the selection or design of Bioresource Technology 99 (2008) 596ñ603; auxiliary equipments and for the tailor made digester. Biochemical Engineering Journal 39 (2008) 121ñ130). Further work is in progress. Single chambered MFC was evaluated at variable • High rate biomethanation of de-oiled cake from organic loading rates at acidophilic and neutral (pH 6 non-edible oil seeds for rapid biogas production and 7) operating conditions using non-coated plain (Sponsored by DST, New Delhi) graphite electrodes (mediatorless anode; air cathode) (Biosensors and Bioelectronics 23 (2008) 1326ñ1332). Major objective of the project is to develop a customized high rate biomethanation technology for biogas • Effect of anodic metabolic function: production using de-oiled cake from non-edible oil seeds Influence of anodic metabolic function viz., aerobic, as the feedstock. Fabrication of two bench scale high anoxic and anaerobic on bioelectricity generation was rate digesters having different working principles and evaluated in single chamber microbial fuel cells (non- design features suitable for the digestion of de-oiled catalyzed graphite electrodes; open-air cathode; Fig 2) cake are the preliminary milestones of the project. during wastewater treatment under similar operating Capacity of the proposed bench scale digesters is 5 kg conditions [Environ. Sci. Technol. 2008, 42, 8088ñ8094].

Figure-1 Figure-2

Biennial Report 2007-2009 83 Bioengineering And Environmental Centre

Despite the fluctuations observed, aerobic metabolic function documented higher power generation compared to anoxic and anaerobic operations. Relatively higher treatment efficiency was also evidenced in aerobic operation. Polarization behavior, bioelectrochemical analysis, sustainable resistance and cell potentials also supported the aerobic operation. The relative efficiency of power generation observed in aerobic microenvironment might be attributed to effective substrate oxidation and good biofilm growth on the anodic surface. Presence of low dissolved oxygen concentration in anodic chamber due to the establishment of equilibrium between substrate oxidation and oxygen scavenging might also contribute positively to power generation in aerobic operation. Fig 5: Cyclic voltammetry curves of anode generated from control, PDB and FDB fuel cell operations using Ag/AgCl as reference electrode (inset figure presents cyclic voltammetry curves of control and PDB operations) (Biosensors and Bioelectronics 24 (2008) 41–47).

• Influence of biofilm growth on anode The effect of biofilm growth and extent of its coverage on the anodic surface was evaluated in a single chambered mediatorless microbial fuel cell (MFC, non- catalyzed graphite electrodes, air cathode, Nafion membrane) for bioelectricity generation using designed synthetic wastewater and chemical wastewater as substrates and anaerobic mixed consortia as biocatalyst [Biosensors and Bioelectronics 24 (2008) 41ñ47]. Three MFCs were operated separately with variable biofilm Fig 3: Single chambered microbial fuel cells (MFC) with open coverage [control; anode surface coverage (ASC), 0%], air cathode and non-catalyzed graphite electrodes. partially developed biofilm [PDB; ASC ~44%; 90 days] and fully developed biofilm [FDB; ASC ~96%; 180 days] under acidophilic conditions (pH 6) at room temperature (Fig 5). The study depicted the effectiveness of anodic biofilm formation in enhancing the extracellular electron transfer in the absence of mediators. Biofilm configured MFC showed to have the potential to selectively support the growth of electrogenic bacteria with robust characteristics, capable of generating higher power yields. PRODUCTION OF BIOHYDROGEN FROM WASTEWATER • Acidogenic fermentation of wastewater Production of biohydrogen from acidogenic fermentation of different types of wastewater viz., diary, distillery, chemical and domestic sewage along with vegetable Fig 4: Schematic details of the experiment setup single of based waste was evaluated in batch mode bioreactors chambered microbial fuel cell [PEM, proton exchange using selectively enriched hydrogen producing consortia membrane; T, preprogrammed timer; PP, peristaltic pump; P, (International J Hydrogen Energy ,, 33 ( 2008 ) 550 ñ sampling/standard electrode port; AM, ammeter; R, resistor 558; Bioresource Technology 100 (2009) 3061ñ3068; (100 ohms); F/RT, feeding and recirculation tank]. International J Hydrogen Energy, 34 ( 2009 ) 3305ñ

84 Biennial Report 2007-2009 Bioengineering And Environmental Centre

3312) (Fig 6). The extent of hydrogen production and showed more positive influence over the corresponding treatment was found to depend on the nature of methanogenic process integration (International J wastewater used and operating conditions adopted. Hydrogen Energy 34 (2009) 1771ñ1779). • Photobiological hydrogen production

Photosynthetic bacteria can produce H2 from organic acids which are abundant in the effluents generated

from anaerobic H2 fermentation. In this direction detailed work was carried out for the development of mixed photosynthetic culture and biohydrogen production from different substrates and operating conditions (International J Hydrogen Energy, 33 (2008) 559ñ569; International J Hydrogen Energy 34 (2009) 1771ñ1779). Nine types of different photosynthetic mixed cultures were acquired from various surface water bodies in and around Hyderabad city receiving discharges from domestic and industrial origin and are characteristically semi-eutrophic in nature with diverse characteristics. Fig 6: Bioreactors used to produce biohydrogen by acidogenic After sampling, the inoculum was enriched with process through wastewater substrate composed of dairy and domestic wastewater (1:1) as mixture along with vitamin solution and • Integration of acidogenic and methanogenic incubated in the presence fluorescent light (International process J Hydrogen Energy, 33 (2008) 559ñ569). Among the Integration of acidogenic H production process followed nine cultures studied culture from one specific pond 2 (HMT Nagar_ sustained for longer periods and showed by methanogenic anaerobic digestion for CH4 production facilitated enhanced energy yield along with higher more efficiency for biohydrogen production. substrate removal efficiency (International J Hydrogen • Benthic type fuel cell to harness energy from water Energy 33 (2008) 2156ñ2166) (Fig 7). Integration of the bodies acidogenic process with photo-fermentation process Feasibility of harnessing bioelectricity from six aquatic eco-systems (Nacaharam cheruvu, Hussain Sagar lake Musi river, Uppal pond/stream and Godavari river)was investigated by employing benthic type fuel cell assemblies (Bioresource Technology 100 (2009) 2240ñ 2246). Experiments were designed with various combinations of electrode assemblies, surface area of anode and anodic materials. Among the 32 experiments conducted, nine combinations evidenced stable electron- discharge/current (Fig 8). Nature, flow conditions and

Fig 7: Schematic details of experimental setup [AcSBBR— Acidogenic sequencing batch biofilm reactor; AnSBBR— Anaerobic sequencing batch biofilm reactor; WDH—Water displacement for H2; WDM—Water displacement for CH4; pH—pH monitoring probe; H2—Hydrogen monitoring probe; FT1—Feeding tank to AcSBBR (pH 6.0); FT2—Feeding tank to AnSBBR (pH 7.0); DT—decant storing tank from AnSBBR outlet; T—preprogrammed timer; PP—peristaltic pump; KOH— Fig 8: Schematic details of the various experimental variations 2N KOH solution] (International J Hydrogen Energy 33 with respect to benthic fuel cell configurations studied (2008) 2156-2166) (Bioresource Technology 100 (2009) 2240-2246)

Biennial Report 2007-2009 85 Bioengineering And Environmental Centre

characteristics of water bodies showed significant reactors. The system was operated with flow rate of 20 influence on the power generation apart from electrode l/day in continuous mode of operation and the retention assemblies, surface area of anode and anodic material. time of each tank was maintained at 24 h (Fig 9). Ecological water bodies could be considered as good During operation, water from all the three stages of platform to harness energy in the form of bioelectricity treatment were analyzed to evaluate the treatment due to the persisting microbial activity. efficiency for treparameters viz., COD, DO, pH, ORP, nitrates, chlorides, phosphates, color, temperature and • Biohydrogen from solid waste TDS. Biohydrogen (H2) from untreated mixed renewable agri- waste using buffalo dung compost was studied.

Maximum H2 production (62.38%) was observed with corn husk with p-value 1.2 x 10-6 revealing its significance at individual and interactive level respectively compared to ground nut shell (GNS) and rice husk (RH). Augmented simplex-lattice design experimentation revealed that a partial supplementation of RH or GNS

to CH improved H2 yield. Modeling studies of H2 production were also carried out. INNOVATIVE METHODS FOR WASTE TREATMENT • Bio-electrochemical treatment Function of microbial fuel cell (MFC) as bio- electrochemical treatment system in concurrence with Fig 9: Ecologically Engineered System designed to polish power generation was evaluated with composite wastewater chemical wastewater at high loading conditions (18.6 g COD/l; 56.8 g TDS/l) in two dual chambered MFCs • Removal of endocrine disruptive compounds (EDC) [non-catalyzed graphite electrodes; mediatorless anode] Endocrine disruptive compounds (EDC) are a wide separately with aerated and potassium ferricyanide variety of chemicals which typically exert effects, either catholytes (Biosensors and Bioelectronics 24 (2009) directly or indirectly, through receptor-mediated 2021ñ2027). Apart from enhanced substrate degradation, processes. They mimic endogenous hormones by relatively good removal of color (31%) and TDS (51%) influencing the activities of hormone even at nanogram was also observed during MFC operation . Apart from concentrations and reported to disrupt the vital systems power generation, various unit operations pertaining to (e.g., the endocrine system) in aquatic organisms. EDC wastewater treatment viz., biological (anaerobic) are present in aquatic water bodies and sediments process, electrochemical decomposition and mainly due to the release of human and animal excreted electrochemical oxidation were found to occur waste. Estriol (E3) removal by adsorption process was symbiotically in the anode chamber. This technology investigated to evaluate the potential of activated may address multiple and diverse problems of charcoal as adsorbent (Journal of Hazardous Materials wastewater treatment by encompassing various unit 164 (2009) 820ñ828). Agitated non-flow batch sorption operations in a single system apart from power studies showed good E3 removal efficiency. generation. • Biological sulfide oxidation by sulfur oxidizing • Ecologically Engineered System (EES) bacteria

Ecologically Engineered System (EES) was designed Evolution of hydrogen sulfide gas (H2S) from anaerobic to mimic the cleansing functions of wetlands and bring treatment of sulfide containing industrial and domestic about wastewater treatment. The system consisted of waste effluents is common waste effluent generated by three tanks containing different strata. As wastewater industries like petrochemicals, tanneries, viscose rayon, passed from one tank to other, various biota in the etc. which contain sulfate and produce H2S during system utilized the nutrients present and brought about anaerobic treatment. H2S has to be removed from treatment. Aquatic and wetland plants, bacteria, algae, waste effluents because of its toxicity and bad odour. protozoa, plankton, snails, fish were used in the system An autotrophic bacteria Thiobacillus sp. an IICT strain to provide specific cleansing or trophic functions. Three was isolated and was used in the studies.[Appl. stages of wastewater was designed with three individual Biochem. Biotechnol. 151, 532-546 (2008), J. Appl.

86 Biennial Report 2007-2009 Bioengineering And Environmental Centre

Microbiol., 106 1280-1291 (2009), Journal of Applied antibiotics should be produced in continuous reactors Sciences 7(15); 2188-2193, 2007, Journal of in which productivity is high. Studies have been carried Environmental Biology 28, 4, 819-823 (2007)]. out using different strategies of culture optimization, mutations, immobilization in different reactors for the GLOBAL CHANGE ñ CLIMATE PROGRAMMES production of gentamycin and oxytetracycline in batch IICT in collaboration with TIFR has set up an semi and continuous mode of operation in a fluidized environmental observatory at TIFR-BF and the bed reactor. programme was supported by ISRO-GBP, to monitor

ozone and its precursor trace gases like NOx, CO and

SO2. The observatory is also equipped with the pyranometer to measure total solar radiation to study the role of photochemical oxidation of these trace gases in the formation of ozone. The station is supported with automatic weather station to monitor the weather parameters like wind speed, wind direction, temperature and humidity. It is being operated from Feb. 2009. More facilities will be added up to strengthen the chemistry of ozone with respect to precursor trace gases. This will help in monitoring ozone mixing ratio in the atmosphere during different seasons to calculate ozone radiation budget. Studies were carried out on the emission of Green

house gases (GHGs) like CH4 and N2O from black and green gram fields located at ICRISAT, Pattancheru. Measurements were carried out for two cropping seasons to evaluate emission factors. Based on the

study Seasonal Integrated Flux E(SIF) for CH4 and N2O was calculated. PRODUCTION OF ENZYMES AND INDUSTRIALLY IMPORTANT COMPOUNDS • Antimicrobial compounds from microorganisms • Antimicrobial products from plants Among all the groups of microorganisms, the To isolate novel antimicrobial compounds work has actinomycetes have proved to be the richest source of been initiated on Ayurveda and ethno botanically antibiotics. Members of the species of Streptomyces important plants to isolate novel antimicrobial produce most of these antibiotics, only a few of them compounds. Studies on Plumbago zylanica extracts are produced by strains of Nocardia and are completed and publication is awaited [Journal of Micronomiospora. The work carried out involved Pure and Appl. Microbiol, 1,95-100 (2007), Process screening of different terrestrial and marine soil samples Biochemistry 42,9, 1352-1356 (2007), International to isolate novel antimicrobial compounds from soil journal of Chemical Reactor Engineering 5: 1-13 (2007), microbes. New potent strains designated as Journal of Basic Microbiology, 48: 53-58 (2008), Critical Streptomyces sp. IICT ñ Strains were isolated and Reviews in Biotechnology, 28: 173-212 (2008), Applied deposited in culture bank. Biochemistry and Biotechnology (In press 2009)]. • Antibiotic production • Microbial hydrolases Production of antibiotics is one of the important areas Enzyme such as lipase and protease production studies of research in applied microbiology and the conventional were carried out in different reactor types such as STR, practice is production in stirred reactors. These systems FBR, PBR and ALR with free and immobilized cells. All have severe limitations such as low yields and long these studies were compared with conventional STR. downtimes. In addition, batch to batch variation of the Aeration and agitation optimization studies were product causes problems for final formulations. Due to conducted for the enhanced production of alkaline these limitations production of antibiotics using these protease production. Scaleup studies were carried out reactors is not economical in batch process. Therefore, in 1.5 liter and 5 liter fermentor by optimizing process

Biennial Report 2007-2009 87 Bioengineering And Environmental Centre

parameters. Production kinetics were also studied and (ninefold increase) in enzyme production by this the results obtained are published in international microbial isolate was noted under optimized journals. environment. • Lipases • Glutaminase production by solid state fermentation Two novel strains were isolated (Rhodotorula Mixture-design impact was investigated for glutaminase mucilaginosa and Brevibacillus sp) for the production of production by isolated Bacillus sp. An augmented lipases. Studies were carried out to produce lipase by simplex centroid design was used to optimize a three submerged fermentation in shake flasks and process (wheat bran, Bental gram husk and palm seed fibre) parameters were optimized. component mixture for glutaminase production. Bengal gram husk was found to be the most suitable substrate • Proteases medium for glutaminase production by Bacillus sp. Protease production using Bacillus subtilis and B. • licheniformis was studied using cultural and kinetic • Xylitol production studies parameters for improvement in yields. Different A natural isolate, Candida tropicalis was tested for xylitol production medium components were done by statistical production from corn fiber and sugarcane bagasse methods like placket and Burman method [Biochemical hydrolysates. Fermentation of corn fiber and sugarcane Engineering Journal, 34, 2 185-192(2007), Bioresource bagasse hydrolysate showed xylose uptake and xylitol Technology, 99, 1776-1786. (2008), Applied production. To simulate influence of hemicellulosic sugar Biochemistry and Biotechnology, 151, 700-710 (2008)]. composition on xylitol yield, three different combinations of mixed sugar control experiments, without the • Enzyme production for eco-friendly leather presence of inhibitors, were performed. To improve yeast processing growth and xylitol production with these hydrolysates, Alkaline protease from Bacillus circulans was purified which contain inhibitors, the cells were adapted by sub and characterized in detail. It exhibited optimum activity culturing in the hydrolysate-containing medium for 25 o at broad temperature range and maximum at 70 C under cycles. After adaptation the organism produced more alkaline pH environment, in the presence of surfactants xylitol. and oxidizing agents. It revealed stain removal property • and dehairing activity for animal hide without chemical • 3-Hydroxy Propionaldehyde (3-HPA) production assistance and without hydrolyzing fibrous proteins. from Glycerol and Glucose (NMITLI project ) This enzyme showed application potential in leather The following three bacterial isolates were isolated by processing industry for production of better quality enrichment studies and deposited in IMTECH product. chandigarh with the following accession numbers for the production of 3-HPA. • Anti-leukemia enzyme production Fermentation process parameter interactions were a. 141B ñ APJ ñIICT Klebsiella pneumoniae deposited evaluated for the production of L-asparaginase by as MTCC 9751 isolated Staphylococcus sp. ñ 6A. Fractional factorial b. 142B ñ APJ ñIICT Enterococcus dispar deposited as design of experimentation (L18 orthogonal array of MTCC 9753 Taguchi methodology) was adopted to optimize nutritional , physiological and microbial fermentation c. 143B ñ APJ ñIICT Raoultella terrigena deposited as factors. The experimental results and software predicted MTCC 9752 enzyme production values were comparable. All selected Apart from Klebsiella pneumoniae, the other two strains factors showed impact on L-asparaginase enzyme namely Enterococcus dispar and Raoultella terrigena production by this isolated microbial strain either at the were found to be new having 3-HPA production capacity. individual or interactive level. Significant improvement

88 Biennial Report 2007-2009 Engineering Services

The Engineering Services Division (ESD) had been providing iii. Automatic Power Factor Correction Panel (225 supporting services for the R&D activities of the Institute kVAR) since its inception and continuing to provide technological iv. 2000Amps LT panel ñ 1 No. inputs and infrastructure facilities. The ESD with all its v. Bus Trunking -1 No. machinery and expertise the division is providing preventive and break-down maintenance with minimum disruption to vi. Cables laid, testing, commissioning and earthing of ongoing R&D activities and in the setting up of new facilities the structure at sub-station & infrastructure for the ever increasing R&D demands of vii. Expansion of HT Switch yard at New Sub-station the Scientists. The ESD had been delivering the goods New Building Electrification works undertaken for: adhering strictly with ISO Quality Management System guidelines. i. Chemical Biology (GF+1F) ii. Genomic Chemistry Lab Besides, ESD is also working on some in-house R&D projects and Prototype Developments on its own in the iii. New Sub-station Building Mechanical Engineering Domain of Lipids Science and iv. New Time office Building Technology. v. Bio-diesel Plant at DRDO Major Activities pursued by ESD vi. Molecular Modelling ï Notional value generated through execution of vii. Combinatorial Natural Products lab approximately 4000 work orders by entire engineering services is Rs. 70 lakhs C. Pump House ï Implementation of ISO ñ 9001: 2000 (and now 2008) model quality assurance system a. New Pump house with 25.0 HPx 4 Nos. and new sump to store the additional drinking water supplies ñ Revision of Department Quality Manuals of 300 kL/day. ñ Policy matters, documentation and trouble shooting b. Utility Services (Water) : Laying of new water ductile ñ MoU with APCPDCL for the erection of 33kV/11kV iron pipe line to the tune of 1.4 km length for the substation in IICT premises drinking water supply. ñ Crisis Management with respect to short fall in power c. Water Utilities : Bore wells reactivated (3Nos.) supply Specialized Equipment /Facilities Added to the D. Carpentry Institute Infrastructure a. Main Building Renovation works A. New DG Sets b. CFC Building 2nos. new DG sets of 500 kVA were added to the c. Chemical Biology institute grid taking total installed capacity to 1990 kVA. E. Machine Shop B. Electrical Modernization of Wet Chemical Labs conforming to Setting up of sub-station III ASHARE 110-95: New workbenches and fume hoods with i. Transformers with OLTC ñ2 Nos. exhaust blowers for NPL (12 Nos) and Fine Chemical ii. 11 kV VCBs ñ 2 Nos. Laboratory (FCL).

Biennial Report 2007-2009 89 Pilot Plant (Upscaling) Facilities

The range of pilot plant equipment covers a whole spectrum of unit operations commonly encountered in chemical process industries, such as distillation, absorption, filtration, evaporation, size reduction, drying, liquid-liquid extraction, and solid-liquid extraction (SLE) units. Chemical reactors of various capacities are designed to operate at different temperatures and pressures are also part of Pilot plant equipment. Material of construction and design conditions of the individual pilot units are carefully selected with a view to enable to handle a wide variety of chemicals. In most instances the pilot plant units are custom designed and erected to suit the specific process requirements. Entirely new pilot plants need to be designed and erected for some special cases. This facility is a prerequisite for acceptance of the process and the very basis of scale up, An inside view of the Pilot Plant design, and retrofitting. capacities, temperature, pressures, are available. Pilot plant In the pilot plant research work, in house I sponsored facilities were provided to major, minor projects (in house projects of the institute are carried out. In this case pilot & sponsored), Ph.D work of students (85) and external plant processes are developed at lab scale and then scaled clients from Industries (15). up to pilot plant level and design data required for In house and sponsored projects such as: Synthetic commercial plant is generated. In addition to in house I aviation Lubricants (SAL), Biodiesel (Jatropha, Karanja), sponsored projects the pilot plant facilities were also Dimeric acid from Castor oil, Lysolethin, Karanja protein rendered to outside parties i.e., bulk drug manufacturers, based products, Hydrazine Hydrate HH), Upgraded rice chemical manufacturers and R&D units situated around bran wax etc ., are being carried out in the Upscaling Hyderabad, for custom synthesis of selected drugs, division. pesticides etc. for clinical I crop studies and commercial External clients I industries like: Ms. Avra Labs, Indus market establishment. Biosciences, Granules India Ltd. Godavari Drugs Ltd, The following facilities are available at pilot plant: Reactor Transgene Bio-tech Ltd., GBS Bio-tech ,Actavis Pharma systems; down stream processing units like distillation manfg. Pvt Ltd, Tamilnadu are the beneficiaries from our units, filters, driers, Spray drier, Autoclaves of varied division.

90 Biennial Report 2007-2009 Business Management

The Business Management (BM) Division's activity is aimed CSIR laboratories offer. Customers were asked to grade at to provide an interface between IICT management, R&D the laboratory on the following parameters with respect divisions and user agencies such as industries (National to the project that they had undertaken with IICT on a and Overseas), government departments and public sector defined scale for Customer Satisfaction Index (CSI): organizations to cater to their requirement of R&D services, Project Objectives: To check if the broad direction of technical, consultancy and technologies. The BM division the achievements intended at the start were undertakes multifarious activities to facilitate IICT accomplished or not ? Time Targets: To ascertain if management to achieve above goals. work is accomplished, as per the time schedule Business Management Divisionís charter is marketing of committed at the start ? Project Outputs: To ascertain IICT knowledge base and technical services to user how much of the minimum tangible which is of value to agencies and prospective clients. Business Management the customer, has been as committed at the start ? Division inputs help directly in achieving External Cash Results Usability: To ensure that the customer is able Flow (ECF) (other than Grant-in-Aid projects) and indirectly to readily use the output without further processing and in publications, patents, technology development, providing with prolonged impact. IICT is one of the seven technological services. The Business Management (BM) laboratories that are categorized in chemical sciences activity helps in projecting the image of institute and in group amongst CSIR labs. achieving the performance of IICT. Major National and Overseas Clients: Major activities performed by the Business Management NATIONAL Division are: Industry BUSINESS DEVELOPMENT ❖ BIOCON Ltd., Bangalore • Business Facilitation ❖ Ranbaxy Laboratories Ltd., New Delhi IICT is one of the few CSIR laboratories, which has six ❖ Andhra Sugars Ltd., Tanuku decades of track record of catering to the R&D and ❖ Nicholas Piramal India Pvt. Ltd., Mumbai technology needs of chemical and allied industries ❖ Dr.Reddyís Laboratories Ltd., Hyderabad (National and Overseas). Business Development activity ❖ in BM Division fulfills this requirement. BM Division USV Ltd., Mumbai interacts with industry/user agencies such as Public ❖ Dabur Research Foundation, Ghaziabad Sector, Government Departments, Defense, Space etc. ❖ Cadila Pharmaceuticals Ltd, Ahmedabad Write-ups, profiles, non-technical notes were prepared ❖ RPG Life Sciences Ltd., Mumbai and sent to industry / user agencies to meet their ❖ requirements. It negotiated with national and overseas Alkali Metals Ltd., Hyderabad clients for providing R&D services i.e. Contract R&D, ❖ MyRna Research Laboratories, Hosur Consultancy and Technical Services. Agreements/MoUs ❖ NOCIL, Mumbai were also executed with clients for providing R&D ❖ Indus Biosciences (P) Ltd., Hyderabad services. B.M. Division was catalytic in earning ECF of ❖ Rs. 7.8 crores (includes Rs.4.11 from overseas) and Natco Pharma Ltd., Hyderabad Rs. 7.73 (includes Rs. 4.5 crores from overseas) during ❖ Alembic Ltd., Vadodara 2007-08 and 2008-09, respectively. Detailed list of new ❖ Sree Rayalseema Hi-Strength Hypo, Kurnool, A.P. contracts signed/assignments undertaken/ completed, ❖ Deepak Nitrates Ltd., Pune technologies / processes demonstrated / released, ❖ Pidilite Industries Ltd., Mumbai reports submitted, etc. are given in Annexures. Public Sector • Customer Relationship Management ❖ IGCAR, Kalapakkam, Tamil Nadu IICT maintains excellent customer relationship with user ❖ Research Center, Imarat, Hyderabad agencies / industry for providing R&D services. IICT charter is to provide quality R&D services and achieve ❖ BHEL, Hyderabad highest customer satisfaction. IICT is able to attract ❖ BPCL, Cherlapally, Hyderabad new customers and retain old customers for providing ❖ TBRL, Chandigarh R&D services. CSIR Customer Satisfaction and ❖ Evaluation Unit (CSEU) monitors the levels of ONGC, Mumbai satisfaction of our clients with R&D services that the ❖ Balmer Lawrie & Co. Ltd., Chennai

Biennial Report 2007-2009 91 Business Management

❖ Visakhapatnam Steel Plant, Visakhapatnam ❖ B.M. Division arranged for printing and procurement of ❖ GACL, Vadodara the following for use of IICT staff: ❖ Bharat Heavy Plate & Vessels Ltd., Visakhapatnam - Work Record Book (2008 & 2009) - New Year Greeting Cards (2008) Govt. Departments INDUSTRIAL CAMPAIGNS & SEMINARS ❖ VSSC/ISRO, Thiruvananthapuram B.M. Division participated / organized Industrial Campaigns ❖ RCI (DRDO), Hyderabad and Seminars held at Hyderabad. ❖ High Energy Materials Research Lab. (HEMRL - DRDO), ❖ Bio-Asia 2008 at HICC, Hitex, Hyderabad (Feb. 7-8, Pune 2008) ❖ Coconut Development Board, Kochi ❖ 13th Human Genome Meeting at HICC, Hitex, Hyderabad ❖ IFCPAR, New Delhi (Sept. 27-30, 2008) ❖ Ministry of New and Renewable Energy, New Delhi ❖ Bio-Asia 2009 at HICC, Hitex, Hyderabad (Feb. 2-4, ❖ Tribal Co-op Marketing Development Federation of India, 2009) New Delhi Seminars ❖ DRDO, Delhi ❖ One Day Conference or Contract Research in Pharma OVERSEAS & Biotech Industry : Scope and Opportunities ❖ Givaudan, Switzerland (March 17, 2008) ❖ Procter & Gamble Home Products, USA ❖ IInd CSIR-Industry meet & CSIR Annual Business Meet ❖ Glaxo SmithKline, UK (ABM) (May17-18, 2007) ❖ Abbot GmbH & Co, Germany ❖ IICT-Industry-DST Workshop on Green Chemistry (Oct ❖ Colgate Palmolive Co, USA 23, 2008) ❖ Evolva, Switzerland PUBLICITY AND PHOTOGRAPHY SERVICES ❖ Aisin Cosmos R&D Co. Ltd., Japan • IICT Open Days (2007 & 2008) ❖ KIGAM, Korea B.M. Division organized IICT open days in August 2007 ❖ UKIERI, Imperial College London, UK and August 2008 for school and college students to depict the scientific developments, achievements and PUBLICATIONS AND PRINTING advancements made by IICT in recent past. The main Business Management Division is actively engaged in objective of organizing this open day was to bring bringing out annual reports, news bulletins, special awareness among the public about the scientific brochures / literature for business development purposes advancements and activities of the institute. B.M. and highlighting the R&D capabilities of IICT. B.M. Division organized guided tour of IICT facilities to Division brought out following important publications: students, visitors, press and media to witness the ❖ IICT Biennial Report - 2005-07 display i.e. colourful posters, exhibits and charts prepared by R&D divisions of the institute. There was ❖ IICT Analytical, Experimental and Infrastructure Facilities overwhelming response from school children for Open (2007) Day. 30 & 20 Schools visited IICT during the years ❖ IICT News Bulletins - 4 issues 2007 and 2008, respectively.

- April 2007 -Sept. 2007, October 2007 -March 2008 • Press & Media - April 2008 -Sept. 2008, October 2008 -March 2009 BM Division arranged for press releases during special ❖ Portfolio of IICT R&D Capabilities and S&T Services events like honours, awards, seminars / symposia, IICT (Dec-2007 & March 2009) Open Days, visits of VVIPís, etc. It also arranged for advertisements in press, souvenirs and journals of sister ❖ B.M. Division facilitated in bringing out seminar laboratories and other organizations on IICT R&D proceedings of the following seminar organized by IICT: capabilities. Notes on important R&D events, technology -Asian Symposium on Medicinal Plants, Spices & Other development, honours & awards etc., were sent to CSIR Natural Products. (Nov-3-6, 2008) Newsletter for printing.

92 Biennial Report 2007-2009 Business Management

• Visit to IICT Facilities IICT i.e., Founderís Day Lecture, Dr. P.S. Murti Memorial IICT is the most sought after chemical science laboratory Lecture, CSIR Foundation Day, National Science Day, in the country for the visitors connected with chemical National Technology Day, National Safety Day, etc. for and drug industry and students pursuing science and the social events organized at IICT staff club, staff engineering education. B.M. Division arranged visits to retirements, IICT school activities, SSB tournaments, IICT facilities for VVIPs, industrialists from India and etc. overseas and students from various parts of the country. • CDs on IICT R&D Capabilities BM Division provided CDs of IICT publications to visitors of IICT for carrying with them to present to their management about IICT R&D capabilities. • IICT Website BM Division prepared CDs of all IICT publications i.e. Biennial Report, IICT News Letters, IICT R&D Capabilities and updated on IICT website for viewing by IICT website users. BM Division also arranged for announcement of IICT Seminars, Training Programmes on website for attracting the prospective participants to avail this facility. • CC TV Facility BM Division is maintaining the closed circuit TV facility in the institute. This consists of a security camera and a producer unit having capacity of mixing video and audio signals to about 20 TV monitors located at prominent places in the institute. BM Division is doing the live coverage of the important programmes like International Seminars / Workshops for the benefit of the staff members who cannot visit the auditorium because of paucity of space. Also, the system is acting as the Electronic Notice Board and all important information like meetings, very important visitors, all OMs like new appointments / transfers / promotions, new arrivals in library etc., are displayed all over the institute. In addition, important visuals / photographs are scanned and shown on the CC TV and programme Jobs undertaken by the Photography Services is monitored on day to day basis. • Management Decision Support Systems • Photography B.M. Division planned, organized and arranged for IICT developed expertise in scientific photography necessary information, documents to institute needed for R&D projects. Business Management Division management decision support systems. has provided photography inputs to R&D divisions for their scientific work and also to research scholars for ❖ Power point presentations to prospective clients their thesis preparation. B.M. Division provided (National and Overseas) on IICT R&D capabilities. photographic inputs for highlighting new facilities created, ❖ Necessary documentation for the approval of demonstration of process technologies to clients, competent authority i.e., Director, Management commercial plants established by IICT clients, clippings Council, Research Council as per the CSIR for IICT video film, etc. B.M. Division also provided guidelines for Technology Transfer and Utilization of photographic inputs for special events organized by Knowledge base. IICT namely agreements / MoUs signed, Independence ❖ Coordination with R&D divisions, Administration / Day, Republic Day and various seminars conducted by Accounts etc., for business management activities.

Biennial Report 2007-2009 93 Business Management

❖ Coordination with CSIR Hqrs (TNBD, RDPD and • Contract Research in Pharmaceutical & Biotech IPMD, etc.) for obtaining necessary approvals. Industry: Scope & Opportunities BM division organized a one day conference on ❖ Participating in organizing committees for conducting ìContract Research in Pharma & Biotech Industry: Scope special events such as seminars / symposia / open & Opportunitiesî at IICT in association with Society of days, etc. Chemical Industry (SCI), Mumbai on 17th March 2008. ❖ Participating in internal committees of IICT such as This major aim of the conference was to provide a Research Planning and Budget, distribution of common platform for the CROs amd emerging Pharma honorarium, Official Language Implementation companies to meet and interact for the mutual benefit. Committee (OLIC), etc. About 100 delegates, including IICT scientists and other members participated in the conference. In technical sessions, very important topics were covered by the NEW INITIATIVES UNDERTAKEN learned speakers; some of these were: Scope and role • IICT/DST/Industry workshop on Green Chemistry of Indian scientist in Contract Research; Venture Capital Business Management Division organized IICT-DST one- in CRO; Will India become a centre for Pharmaceutical day industry interactive workshop on Oct 23, 2008 at Research and Development; Biotechnology Incubation- Hyderabad with theme of ìGreen Chemistryî The Global Development and Challenges; Biotechnology objective of the workshop was to listen to the problems Incubation Centre, Hyderabad - a PPP facility for entrepreneurs, industrialists for technology development faced by the industry (in Hyderabad region) and provide and upscaling; Opportunities for CRO in India for Pharma scientific solutions to those identified problems. Based & Biotechnology, etc. The conference concluded with a on this exercise, it was proposed to generate panel discussion. collaborative projects (between industry and academic/ • national labs). DST will be funding the identified projects Public Private Partnership for Utilizing IICT Chemical Biology R&D Facilities (to academic institutions/national labs) to solve the industrial problems whereas the industry is expected BM division has initiated dialogue with a private firm to provide data and other logistic support. Industry is Biopolus Life Sciences Limited, Bangalore for utilisaton of R&D facilities of Chemical Biology Lab. Bioplus is expected to adopt these solutions at their own cost. engaged in carrying out R&D in the field of Biology, Advisor DST, Advisor APIIC, Director Jeedimetla Effluent Molecular Biology & Genomics. IICT has set up Treatment Plant (JETL), Director, IICT & senior scientists chemical biology group & laboratories facilities in 2005 of IICT and President, BDMA participated in the and equipped it with state of art facilities. Bioplus after workshop. More than 60 industry representatives seeing the facilities and scientific expertise available at participated in the workshop and made presentations IICT desired to utilize chemical biology equipment facility on problems faced by industry. Later, panel discussions and consultancy services for development of new were held by experts to identify the major issues faced products and processes. After negotiations, IICT and by the industry and means of addressing the same. Bioplus entered into agreement in Aug-2008.

94 Biennial Report 2007-2009 Research Management

The Research Management (RM) Division is the nerve during the period in the area of contract R&D/ centre of IICT Management, handling major portfolios like Consultancy/Grants-in-aid projects. RM division Project Management, Resource Management, HR facilitated in executing agreements for joint research Management, Intellectual Property Management, projects in support of R&D programmes between IICT International S&T Affairs related to R&D Projects and and various international institutes during the last 2 Bilateral Exchange Programmes, Coordination of TLEP of years for its research in Chemical Sciences & CSIR, Foreign Deputations of Scientists, Customer Technology apart from R&D collaborations. Satisfaction Evaluation of Externally Funded Projects, Incentive Schemes such as Formulation of Awards and INTERNATIONAL ACADEMIC COLLABORATIONS Distribution of Intellectual Fee/Royalty/Honorarium, RMD looks after the IICT- Academic Institutes collaborations Organization of Institutional Events, Preparation of Five both Indian and overseas such as: Year Plan and Annual Plan documents, RC Agenda, to name a few. Various activities, functional performance and • Indo-French Joint Laboratory Agreement between achievements during the period (2007-09) are given below: IICT & University of Rennes, France PROJECT MANAGEMENT The main objective of setting up of this Laboratory is to develop new reactions, processes and novel Planning, Monitoring and Evaluation (PME) of R&D projects, technologies for sustainable chemistry where scientists activities and assignments are undertaken by the Research from both India and France will work in the fields of Planning and Budget Committee and the Research Council Chemical Biology, Molecular Photonics and Bioactive of the Institute with the interactive participation and active Natural Products and Medicinal Chemistry with involvement of RM Division, which provides necessary key relevance to national molecular bank facility on data & information inputs. The XI Five Year Plan document combinatorial natural products being created at IICT, of IICT has been compiled by RMA with the inputs / project Hyderabad. proposals from R&D Divisions. IICT has identified six R&D Sectors for its XI Five Year Plan under National Laboratories • Indo-Australian Joint Laboratory Agreement Scheme formulated by CSIR, sanctioned with an outlay of between IICT & RMIT University, Melbourne, Rs. 75.00 crores approx. Australia IICT and RMIT collaboration in research and training in IICT is also the participating Laboratory for some of the Environmental Science and Technology include: Network and Rural development Projects which are coordinated by other CSIR labs as Nodal labs. RMA is ï Focus on the establishment of a joint Ph.D training maintaining a unique user friendly website, networked project programme. data and information system which is accessible to all ï Establishment of a joint Research Laboratory where, scientists and the management. The website designated special emphasis is given on catalysis, High Field Solid as Technical R&D/RMA-Net caters to the total R&D State NMR studies and Nanoscience/Nanotechnology. management portfolio of the laboratory covering data on The fields of collaboration include, water quality & projects, IPR, HR, International S&T Collaborations & wastewater treatment, air pollution control, control of Projects, XI Plan Projects, Project Reports, such as, ECF, greenhouse gas emissions, renewable energy and Publications, Patents, Lab Reserve, Technologies/ impact of climate change on coastal urban areas. Processes Developed/Demonstrated, etc. Every year Annual R&D Plan of IICT including the preparation of budget and • Indo-Japan Joint Laboratory Agreement between revised budget is prepared by RMA. RM Division maintains IICT & National Institute for Material Science, the complete database of all projects with fund sanction NIMS, Japan and receipts, expenditure, deployment of temporary The main objective of the collaboration is to create a manpower, regular staff, patents, foreign deputations, R&D breakthrough in collaborative research on the ìChemistry achievements/ information of the staff of the laboratory, of Nanoporous Materialsî. This includes: equipment & infrastructure facilities. RMA through the RPBC ï Exchange of researchers to execute the research (Research Planning & Budgetary Committee) conducts R&D Divisional Review meetings for performance evaluation and ï Exchange of information through joint seminars and budgetary allocation. joint publications on the research outputs • Major Laboratory Projects ï Joint research proposals IICT undertook over 87 new projects / assignments ï Implementation of cooperative research.

Biennial Report 2007-2009 95 Research Management

The Materials Research Centre plan also includes: RM Division has processed 114 project proposals, out ï To engage highly talented and outstanding young of which 79 have been funded with a total sanction of researchers from India to perform research in the field Rs. 27.74 crores for 3 years. of fuel cells, smart and corrosion materials and • Liaison/Coordination with Grants-in-aid Agencies theoretical research. such as DST, DBT, MOE&F. ï To construct an excellent research atmosphere for ❖ Scrutiny and forwarding of project proposals to young, brilliant and outstanding young researchers in Grants-in aid agencies for funding. India to execute their own research in their home ❖ countries for NIMS with little budget and Partial travel grant to scientists to attend international conferences. ï To attract and recruit the next generation of young ❖ research leaders to NIMS, Japan. Preparation and onward transmission of Expenditure Statements and Utilization Certificates. RM Division monitors the physical & financial progress of Grants-in-Aid projects and corresponds with various • Research Data Reports to CSIR funding agencies for timely release of funds. The R&D achievement reporting is done monthly, RMA INITIATIVES quarterly and annually to CSIR. ❖ • Interaction with Young Scientists Monthly R&D Achievement Reports. ❖ An interactive meeting with young scientists was Quarterly & Annual Research Utilization Data. organized in the presence of Dr. J.S. Yadav, Director ❖ Instituteís Annual Report and R&D achievements and Dr. A.C. Kunwar, senior most Director Grade information for CSIR Annual Report. Scientist and Head, NMR and Mrs. C.B. Lakshmi, Head RMD, to address the youngsters regarding the new HUMAN RESOURCE MANAGEMENT opportunities/challenges in the emerging areas of basic • RM Division also looks after the human resource science/applied research in CSIR. This was to brief management of the institute which facilitates and looks them about IICT/CSIR mandate. CSIR system/ after deployment of hired manpower i.e. Project procedures, incentives in recognition for their Assistants and Research Fellows (Project) in Externally outstanding contributions in research and development Funded Projects, by coordinating the engagement of were also highlighted. In order to promote and nurture Project Assistants against projects and their further the inventive and innovative spirit among the young extension of tenure on need basis. The Division scientists, the focus was laid on competitiveness in processes applications for joining as JRF, SRF (for basic research as evident from the global share of India Ph.D programme), RA, Project Assistants, Student in publications in journals included in Science Citation Trainees (for project work) and at the end of the tenure Index (SCI). Thus, to enhance the quality of research, they are given certificates with appropriate citations, the emphasis was laid on improved productivity and which is akin only to IICT. Apart from the above, the value addition through technology and frontline research. Division also processes: RMA has also initiated by inviting research proposals ❖ Recognition of IICT as Research Centre in various under the IICT scheme ì Prolog to Discoveryî in which Indian Universities. Rs. 4 to 5 lakhs funding will be given to scientists to ❖ Recognition of guideship of scientists in various try out their basic research ideas. This will give them Universities. an opportunity to apply for external funding with the research results obtained through this scheme. ❖ Student Trainee Programme for B.Tech, M.Tech, • B.Pharm, M.Pharm, M.Sc, & M.B.A students from New R&D Project Proposals to Government Funding various Universities / Affiliated Colleges, IITs, NITs, Agencies etc. RMD gives wide publicity regarding information of various • opportunities/ avenues available for R & D funding by DST Fellowships / Projects various agencies through RMA Net. Scientific staff Concerted efforts and interaction of RM Division with desirous of submitting new R & D project proposals for the scientists for applying for various Fellowships / financial support to various central and state government Projects through wide publicity have resulted in getting funding agencies in challenging areas, submit their almost all the project schemes and fellowships funded proposals to the RM Division, for their scrutiny and by DST to IICT scientists, under various programmes obtaining the approval of competent authority. Likewise, like:

96 Biennial Report 2007-2009 Research Management

❖ Fast Track Scheme • Quality Management ❖ Women Scientists Scheme IICT has been certified by TUV India Private Limited for ISO 9001: 2000. RM Div. undertakes the documentation ❖ Young Scientists Research Scheme and safe custody of commercial ISO reports archives, ❖ SERC so that, quick retrieval is possible as and when required. ❖ Ramanna Fellowship • Awards / Honours ❖ Ramanujam Fellowship RM Division is involved in formulation of guidelines for the performance awards instituted by IICT for various ❖ J C Bose Fellowship groups of staff and these awards are given on the IICT ❖ Swarnajayanti Fellowship Foundation Day & CSIR Foundation Day. Forwarding of nominations for various awards at national level such International S & T collaborative projects with almost as Bhatnagar/CSIR Young Scientist/Technology prizes, all the countries such as Australia, France, etc. are etc. is also being handled by RM Division. taken up by the Division. • Data Base Management RM Division also maintains Management Information System for ECF, Projects, Permanent and Temporary Staff, Awards / Honours, Patents filed / Granted, Customer Satisfaction Reports, Foreign Deputations, etc. for monitoring the project and providing information feedback to Director, IICT and to CSIR Hqrs. and other Ministries, as and when required. • Intellectual Property Rights IICT has recognized the importance of the IPRs by filing patent applications in India and overseas. RM Division enthuses scientists working in various divisions of the laboratory for filing patent applications by rendering guidance and assistance in drafting, scrutinizing and Dr. S. Chandrasekhar (left) is receiving the NASI-Reliance sending the patent applications to IPM Division at CSIR Industries Platinum Jubilee Award -2008 Hqrs. Concerted efforts for filing and follow-up have resulted in filing good number of patents in India and • International S&T Activities abroad and also licensing of one patent to M/s IPCA Research Management Division interfaces with IICT Laboratories, Mumbai. scientists and ISTAD at CSIR Hqrs. on all matters CUSTOMER SATISFACTION EVALUATION (CSE) connected with the International Science & Technology collaborations of the laboratory, like Customer evaluation of projects is a significant part of ❖ Project Management as feedback from the customer is International bilateral project proposals vital for better & timely deliverables and also gives a scope ❖ Security and sensitivity clearance of international for improvement in deliverables. This activity involves a lot bilateral projects of follow-up of clients to get the CSE reports from them. ❖ Bilateral DST projects Concerted efforts of RM Division has resulted in getting ❖ Permission of DG, CSIR for holding international good feedback from many clients putting IICT in No. 1 conferences in IICT. position among CSIR labs, in project performance during ❖ the period 2007-08. Conference funding ❖ Visits of foreign scientists/ research scholars and • Customer/FundingñSource Interface Management their CSIR/ MEA clearance. Customer Satisfaction Evaluation (CSE) was done for • 58 projects completed during 2007-08. An average CSE Foreign Deputations grading of the institute during the year 2007-08 is 4.26/ IICT scientists are deputed to attend various important 5. IICT stands at 1st place in grade point average among international seminars/workshops and also for training CSIR chemical labs. on sophisticated analytical instruments and to work with fellow scientists in reputed overseas universities.

Biennial Report 2007-2009 97 Research Management

135 Staff members were deputed abroad during the • Organization of Technology Led Entrepreneurship reporting period. RM Division coordinates in obtaining Programme (TLEP) necessary approvals and clearances for these CSIR has entrusted the job of organizing TLEP at IICT deputations. Subsequently, RM Division collects visit once in every year for a period of 5 years starting from reports from the deputed scientists, scrutinizes them the year 2008 onwards. HRDG of CSIR in collaboration and forwards to CSIR. with IICT organized Fifth Technology Led st th • Organisation of Institutional Events/Functions Entrepreneurship Programme during 1 June to 26 June 2008 at IICT, Hyderabad. The objective of this During the period, RM Division organized the PS Murti programme is to inculcate the spirit of entrepreneurship/ Memorial Lecture, National Science Day, Bhatnagar intrapreneurship amongst research scholars, so as to Memorial Lecture, National Technology Day, Sidhu enable them to learn how to take knowledge based Science Lecture, IICT Foundation Day, CSIR Foundation innovation, through a commercial outcome, managing Day and Founderís Day Lectures, where eminent all the major steps on the way. The skills learned during scientists / academicians delivered the lectures. Details this programme would help them to enhance their are given in the Annexures. expertise in technology commercialization and business development. The spirit of intrapreneurship in the participants would make them to take entrepreneurial roles in large organizations in the course of their employment subsequent to completion of their doctoral programme. The training programme is conducted by the faculties largely drawn from IIMs.

Dr. A.C. Kunwar, Acting Director, IICT is presenting a memento to Prof. Khakhar during the P.S. Murti Lecture (2009)

Inauguration of Technology Led Entrepreneurship Programme

• File Management and Safe Custodial Activity The project data/information of various in-house and externally funded projects is maintained very systematically by Research Management Division apart from the project reports and process know-how and design documents. In addition, Patent Files, Agency Prof. S.N. Puri delivering the CSIR Foundation Day Lecture Queries, HR/Awards Files are maintained. Total 1600 • Mobilisation of Funds files are being maintained, which can be retrieved RM Division handles mobilization of funds for organizing through computerized data base system. Technology Seminars, Workshops, Conferences both at National Transfer Documents, Know-how and Design Reports, and International levels, by contacting various funding ISO documented files are kept in safe custody in a agencies like, CSIR, DST, DBT , INSA, BRNS and systematic manner permitting a quick retrieval for use, interested industries and ministries. as and when required.

98 Biennial Report 2007-2009 Information Management

IICT - CCMB Library is a combined facility for two National Reports, CDs received through print subscriptions, Ph.D Laboratories, IICT and CCMB and has precious thesis etc. internationally acclaimed reference collections in frontier SciFinder areas of chemical, engineering and life sciences. It plays It is a paid database from American Chemical Society. a vital role in acquisition, organization, and dissemination SciFinder is a research discovery tool that allows the user of knowledge. It is consulted not only by the Institutional to explore the CAS databases that contain literature from users but also by researchers in and around Hyderabad. It many scientific disciplines, including biomedical sciences, has an impressive collection of both of print and electronic chemistry, engineering, materials science, agricultural resources including books, journals, technical reports, science etc. One can explore one single source for standards, patents, theses and other material. It has scientific information in journal and patent literature from adequate infrastructure to meet its requirements. The main around the world. thrust of the library continues to be the improvement of the Following are the special tasks that have been achieved quality of services and facilities, achieving higher degree of during the period. userís satisfaction and modernization of its activities and E-Resources operations. By virtue of E-Journal consortium of CSIR, IICT scientists Print holdings include books, dictionaries, handbooks, can access around six thousand journals in their desktops. encyclopedias, reference book series and back volumes Access to few more on-line journals are made available by of journals. These total print collections are more than a the library as add on to print subscriptions of IICT. lakh in number. Library subscribes to around 400 National CA on CD and International journals. Chemical Abstracts on CD-ROM (CA on CD), provides the The library is one of the few signature libraries in Andhra user with complete access to the Chemical Abstracts on Pradesh, which has a complete collection of Chemical easy-to-search CD-ROMís. CA on CD includes a broad Abstracts from the year of its inception i.e. 1907. Libraryís spectrum of technical and scientific information including computer infrastructure has been upgraded and user rooms Biochemistry, Physical, Inorganic, and Analytical Chemistry, were created in Library to facilitate usage of CD-Rom Applied Chemistry and Chemical Engineering, databases and browsing of E-Resources. Online databases Macromolecular Chemistry, and Organic Chemistry. and E-Journals are made available at Userís desktops. References may be in the form of journals, patents, technical reports, dissertations, conference proceedings, DATABASES and books. It is updated monthly and includes indexing The CD-Rom databases include Chemical Abstracts, Indian information. Each monthly update contains all the and ASTM Digital Library, collection of Companyís Annual information for the calendar year-to-date.

Biennial Report 2007-2009 99 Information Management

ScienceDirect DRI: Digital Repository of IICT As the e access to Science Direct was discontinued (DRI), is a digital archive of the research output of IICTís through CSIR consortium, alternate arrangement by scientists, has been designed and initiated. It is a subscribing to the most referred Science Direct journals mechanism for making research more widely available to along with their e version was made to satisfy the Science academics and others. This knowledge base covers journal Direct journal requirement of the Instituteís users. Other articles, technical reports, presentation/lectures, preprints, journal articles required by the users have been provided Thesis, images etc. One can browse the documents by from the other Libraries of CSIR and other organizations at author, division, subject and date. Both simple and the earliest by procuring a copy through cooperation. advanced search facilities have been provided. Publications Web of Science from the year 1990 till 2007 and PhD Thesis from the year The Web of Science was provided through CSIR 1945 till 2008 are available. Publications of remaining years, consortium, provides seamless access from approximately Newsletters, Annual Reports, Biennial Reports till date etc 10,000 of the most prestigious, high impact research will be scanned/uploaded shortly. The software that was journals in the world along with a unique search method, chosen amongst the landscape of software platforms for cited reference searching. With the help of ìAnalyzeî tool, building DRI is Dspace (Dspace 1.5) with Java, Apache publication and citation data can be analyzed by several Ant, PostgreSQL, and Apache Tomcat on Linux OS. fields. Beilstein CrossFire Patent Databases CrossFire Commander and CrossFire Server are an Through E-Journal consortium two major patent databases integrated client/server application for searching the are available to IICT researchers namely Derwent World CrossFire Database. It represents a unique, deeply indexed Patents Index and Delphion. Derwent database is source of experimental data in organic, inorganic and searchable to give patent titles and abstracts using clear, organometallic chemistry. It contains: descriptive, industry-specific terms. Delphion with patent collections & searching options analyses the data providing Substances new insights into retrieved results. These are available at Fully searchable chemical structures. Substance records users desktops. show physical, chemical and bioactivity data ñ including Library Home Page pharmacodynamics and (eco-) toxicology data from different publications. Library Home page http://libdoc was designed and maintained by this division serves as a one point access Reactions to all the above E-Resources mentioned. Its features have Fully searchable single and multi-step reactions, many been enhanced by adding more utilities. with reaction procedure texts. One of the important features is the addition of ìsearchî Citations facility for retrieving desired parameter of the research output Indexed from the primary organic, inorganic and (i.e. Publications/Patents/Theses) of IICT from the available data. Search of publications can be done by Author or organomatellic chemistry journal literature going back to Journal Title or Year or Keyword. More than Seven thousand 1772 and patent literature. (7,000) entries are available. Ph.D Theses can be searched Archiving of IICT Publications either by Title, Guide, Author or Year. Patents data search It is essential to preserve IICTís research outputs and can be searched by Title, Inventor, Reference Number and make it readily available for reference. Reprints of research Date of Approval. This project is developed in JAVA (JSP, papers of IICT scientists are collected/ downloaded from Servlets, Jdbc) with back end of MS SQL Server 2000, source publications, indexed and bound into volumes and Web Logic Server and operating system is Windows 2000 Server. displayed in the library. Besides E-Journals subscribed by the Library, access has IMA Services to Industry & Outside agencies also been provided to various open access journals and IMA provides library utilization facilities to industries, and other information related to Chemistry and Chemical other agencies on membership basis. Apart from internal Sciences which are freely available on the Internet. Trial users, library facilities have been extended to research access of several databases and E-Journals have also scholars from any university registered for Ph.D and been provided for the benefit of users as and when available. corporate sector through membership in the library.

100 Biennial Report 2007-2009 CSIR Network Projects

A. GREEN TECHNOLOGIES FOR ORGANIC CHEMICALS on sponsorships basis. (CMM-006): B. GLOBALLY COMPETITIVE CHEMICALS PROCESSES This project was conceived and identified by CSIR with AND PRODUCTS (COR-003) IICT as nodal laboratory based on the expertise and The project was undertaken during the 10th Five Year competence available within CSIR laboratories for Plan with IICT as the nodal laboratory. The other implementation during 10th Five Year Plan. The other participating labs are NCL, NEERI, IHBT, CSMCRI, RRL participating labs are CIMAP, IHBT, IIIM (RRL, Jammu), (Trivandrum), RRL (Bhubaneswar), RRL (Jammu), IIP, NEIST (RRL, Johat), NIST (RRL, Thiruvananthapuram), CIMAP and CFRI. The major objectives of the project NCL, CSMCRI, CFRI, RRL (Bhubaneswar), CECRI, IIP are to develop globally competitive chemical entities, and NEERI. The major objectives of the project are to processes and products of high commercial value. The develop new products/process/catalysts/ reagents/ research in this Network project led to the development techniques, which attribute green concept, making of 18 processes, 3 of which were transferred .The project feasible green products and processes. The constituent also resulted in 8 Patents (filed), 42 research CSIR laboratories collectively developed 16 Technologies publications, facilitated in 9 Ph.Ds and the training of out of which 6 technologies were transferred. This 22 students. network project also resulted in 41 research publications, 5 patents and facilitated the award of 9 IICTís contributions to the network project is as follows. PhDs. Technologies/Processes developed & transferred IICTís, contribution to the Network project is as follows: ❖ Upscaling of Taxol side chain and Technologies / Processes developed & transferred ❖ Diltiazem using the supported catalysts. ❖ Heptafluoropropane - Demonstrated to Sponsor Lab scale and bench scale demonstration for the DRDO above processes have been given to Sponsors SMS ❖ Trifluoroethanol-Demonstrated to Sponsor NFI, Surat Pharmaceutical Pvt. Ltd ., Hyderabad Technologies / Processes developed Technologies/Processes developed ❖ HFC-32-Process optimized at laboratory level ❖ Ammoxidation of p-methyl anisole to p-methoxy benzonitrile at laboratory scale. ❖ Bench scale fermentation process for the production of L-lactic acid using waste potato starch (generated ❖ Oxidation of cyclohexane to benzene from potato processing industries) Co or Au anchored SBA-15 catalysts yielded >15% ❖ Preparative methods are developed for (E)11- cyclohexane conversion at 1 MP pressure in the Hexadecene-1-ol, (E)11-Hexadecenyl acetate to temperature range of 50 to 1600C under batch control a serious pest on Brinjal, Brinjal Shoot & conditions. Fruit Borer (BSFB) (Leucinodes orbonalis) ❖ Methanol / DME synthesis ❖ Synthetic routes are established for the preparation Catalyst composition and methodology was of (E,Z)-4,7-Tridecadienyl acetate and (E,Z,Z) - 4,7,10 indentified for the synthesis of Methanol / DME at -Tridecatrienyl acetate, the two pheromone laboratory level. components of greasy cutworm (Agrotis ipsilon), a serious test on vegetable crops. ❖ Dipotassium Rhodizonate, Dipotassium Croconate, Barium Croconate Croconic acid dyes have been ❖ Gamma linolenic acid from agro products. prepared at gram level for NIR dyes. Processes are ready for release to interested clients Processes are ready for release to interested clients on sponsorships basis.

Biennial Report 2007-2009 101 NIPER, Hyderabad

National Institute of Pharmaceutical Education and • To prepare professionals to suit to the need of Research (NIPER), is functioning with IICT as its mentor pharmaceutical industry institute, in terms of the M.O.U. between the CSIR and • Expose the students and scholars to high tech areas Department of Pharmaceuticals, Ministry of Chemicals & such as drug discovery, pharmacogenomics, Fertilizers, Government of India, New Delhi. It is one of the toxicogenomics, RNAi & DNA technology, six NIPER like institutes, which have been setup by the bioinformatics, drug design and molecular modeling, Ministry in 2007. As a NIPER like institute, NIPER, molecular biology and herbal research etc. Hyderabad has the status as a center of excellence for higher education, research and development in • Develop and practice e-learning for the professionals pharmaceutical sciences. It has the following as its and training for teachers, researchers, regulators in the objectives : respective fields. • Enhancement of creativity, motivation, drive and inculcate • Create a world class institute of teaching and research professionalism in the field of pharmaceutical Sciences. • To bring synergy between academic, R&D, technology It offers M.S. (Pharma) 2 years course, in the specialization and industry through training and exposure for such of Medicinal Chemistry, Pharmacology & Toxicology and environment. Pharmaceutical Analysis. The selection for admission to this course is through JEE for NIPER-Mohali. Presently, it • Bridging collaborations between pharmacy, has 45 students of IInd year and 57 students of Ist year. It is biotechnology, information technologies and prepare for expected that the Ph.D programme may commence in meeting global challenges early 2010.

102 Biennial Report 2007-2009 Human Resource Development

Biennial Report 2007-2009 103 104 Biennial Report 2007-2009