DOCSLIB.ORG

Active-Site Zinc Ligands and Activated H20 of Zinc Enzymes (Amino Acid Sequence/Metalloenzymes/Metalloproteins/Structure-Function/X-Ray Crystallography) BERT L

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Active-Site Zinc Ligands and Activated H20 of Zinc Enzymes (Amino Acid Sequence/Metalloenzymes/Metalloproteins/Structure-Function/X-Ray Crystallography) BERT L Proc. Natl. Acad. Sci. USA Vol. 87, pp. 220-224, January 1990 Biochemistry Active-site zinc ligands and activated H20 of zinc enzymes (amino acid sequence/metalloenzymes/metalloproteins/structure-function/x-ray crystallography) BERT L. VALLEE* AND DAVID S. AULD Center for Biochemical and Biophysical Sciences and Medicine and Department of Pathology, Harvard Medical School, and Brigham and Women's Hospital Boston, MA 02115 Contributed by Bert L. Vallee, October 10, 1989 ABSTRACT The x-ray crystallographic structures of 12 Table 1. Reported crystal structures of zinc enzymes zinc enzymes have been chosen as standards of reference to Class Type identify the ligands to the catalytic and structural zinc atoms of other members of their respective enzyme families. Univer- I Oxidoreductase sally, H20 is a ligand and critical component ofthe catalytically Alcohol dehydrogenase active zinc sites. In addition, three protein side chains bind to II Transferase the catalytic zinc atom, whereas four protein ligands bind to the Aspartate carbamoyltransferase structural zinc atom. The geometry and coordination number III Hydrolase of zinc can vary greatly to accommodate particular ligands. Carboxypeptidase A Zinc forms complexes with nitrogen and oxygen just as readily Carboxypeptidase B as with sulfur, and this is reflected in catalytic zinc sites having DD carboxypeptidase > = Thermolysin a binding frequency of His >> Glu Asp Cys, three of Bacillus cereus neutral protease which bind to the metal atom. The systematic spacing between ,B-Lactamase the ligands is striking. For all catalytic zinc sites except the Alkaline phosphatase coenzyme-dependent alcohol dehydrogenase, the first two lig- Phospholipase C ands are separated by a "short spacer" consisting of 1 to 3 IV Lyase amino acids. These ligands are separated from the third ligand Carbonic anhydrase I by a "long spacer" of -20 to -120 amino acids. The short Carbonic anhydrase II spacer enables formation of a primary bidentate zinc complex, V Isomerase whereas the long spacer contributes flexibility to the coordi- None nation sphere, which can poise the zinc for catalysis as well as VI Ligase bring other catalytic and substrate binding groups into appo- None sition with the active site. The H20 is activated by ionization, polarization, or poised for displacement. Collectively, the data may relate to the specificity of these enzymes and their imply that the preferred mechanistic pathway for activating the of action. water-e.g., zinc hydroxide or Lewis acid catalysis-will be mechanisms determined by the identity of the other three ligands and their spacing. MATERIALS AND METHODS Computer and literature searches have served to ascertain In the last three decades the biological role of zinc, like that sequences, zinc content, and functional characteristics of of a number of transition metals, has become most readily families of enzymes corresponding to those of known struc- apparent in enzymatic catalysis. Zinc is the only metal, ture. A family of enzymes is here defined as a group of however, that is essential in the function of at least one their enzyme in each one of the six classes established by the proteins related by common ancestry as revealed by International Union of Biochemistry. Among these zinc homology and with identical or very similar functions. Both enzymes, the hydrolases are most abundant. Zinc enzymes the National Biomedical Research Foundation and Gen- occur in all phyla, leaving no doubt regarding the essentiality Bank/Los Alamos data base files of the Molecular Biology of this element to all forms of life. Computer Research Resource at Harvard Medical School Unambiguous identification ofzinc ligands and their modes were employed. The number of enzymes explicitly shown to of coordination both at the active and structural sites of zinc contain zinc by metal analysis and ofothers whose content is enzymes has been accomplished by x-ray crystallographic putative and inferred, based on their inhibition by metal- analysis. All other experimental approaches had proven to be binding agents and/or activation with zinc, greatly exceeds unsatisfactory. Structures have now been obtained for 12 the number of enzymes whose three-dimensional structures zinc enzymes representing four of the six enzyme classes have been determined. (Table 1). For these the details of coordination are now thoroughly known, and their structures therefore represent standards of reference. We here examine the zinc ligands at RESULTS the active sites of these enzymes and compare them with In the following, carboxypeptidases A and B of bovine those in the sequences of other members of the same protein pancreas, thermolysin, the neutral protease of Bacillus ther- family. The results should ultimately permit conclusions moproteolyticus, the neutral protease of Bacillus cereus, regarding the conformations of the protein ligands that are carbonic anhydrases I and II of human erythro-tytes, and the required so that they can interact with zinc; these, in turn, dimeric alcohol dehydrogenase of horse liver serve as the The publication costs of this article were defrayed in part by page charge Abbreviation: L1, L2, L3, and L4, the first, second, third, and fourth payment. This article must therefore be hereby marked "advertisement" zinc-binding ligand, respectively. in accordance with 18 U.S.C. §1734 solely to indicate this fact. *To whom reprint requests should be addressed. 220 Downloaded by guest on October 2, 2021 Biochemistry: Vallee and Auld Proc. Natl. Acad. Sci. USA 87 (1990) 221 69 72 196 In contrast to the carboxypeptidases, in this instance two histidine residues, His-142 (L1) and His-146 (L2), are nearest Bovine A LG I SR IW I T F LS I SYSa neighbors, separated by a short spacer of 3 amino acids; the * Rat Al TG SR VW V T F I S I S Y S Q 19 residue long spacer of thermolysin between His-146 (L2) and Glu-166 (L3) is significantly shorter than that of carbox- Rat A2 AG IAR V~NV V T F TL SYSQ ypeptidase. In all bacterial neutral proteases sequenced so far, five of the eight residues bordering Glu-166 (L3) are Bovine B C G FF AAR VW I S Y LT I SYSa identical, and the other three are closely similar (Fig. 2). Thus the short and long amino acid spacers are constant and Crayfish B GG I AR VN I A Y LT F S Y S Q characteristic for each metalloprotease family. However, RatB CGF AR VN I S Y LT 1| SYSQ while the metal ligands for both families are identical, 2 histidine and 1 glutamic acid, their order in the sequence (His, FIG. 1. Zinc ligands of carboxypeptidases. Lightly shaded boxes Glu, His versus His, His, Glu) is not; the other details pointed denote the enzyme(s) x-ray standard of reference for each family. out also differ distinctly. This contrasts with the mechanistic Asterisks denote those for which zinc was not measured directly. similarities that have been emphasized; the potential signif- Black vertical columns indicate the proposed metal binding ligands icance of these structural identities to those of function based on the structure of the standard of reference. requires further exploration.t Class IV: Lyases. X-ray crystal structures have been re- standards of reference for those members of their respective ported for-two of the three forms of carbonic anhydrase (EC families of known sequence but unknown three-dimensional 4.2.1.1)-I (9) and 11 (10)-present in human erythrocytes. structure. Our specific objective here is to compare the In this case three histidines bind the zinc ligands, and again identities of the zinc ligands at their putative catalytic and a H20 molecule fills the fourth coordination- site. A single structural zinc-binding sites and the amino acid sequences in amino acid short spacer separates L1 (His-94) from L2 their immediate vicinities. However, we stress some general (His-96); the seven amino acids surrounding these ligands in implications of our findings that may pertain to the functions 15 different carbonic anhydrases are 95% similar (Fig. 3). A of zinc and other metal active sites and, hence, the design of 22-amino acid, long spacer arm supplies L3 (His-119). Four of enzymatically active model systems and the discernment of the eight amino acids surrounding it are identical for 15 the mechanisms of such enzymes. carbonic anhydrases sequenced, and the remaining four Class III: Hydrolases. Metalloexoproteinases. Carboxy- amino acids show a high degree of similarity. peptidase A (EC 3.4.17.1) has been considered a prototype Class I: Oxidoreductases. Horse liver alcohol dehydroge- for all zinc proteases (1, 2). It contains 1 mol of zinc essential nase (EC 1.1.1.1) is a NAD(H)-dependent dimeric enzyme for activity per mol of Mr 34,600. X-ray structure analysis of containing two zinc atoms per monomer. It represents the the bovine A and B enzymes has revealed that zinc binds to only zinc enzyme examined by x-ray crystallography (11) so the same three protein ligands (L1-L3) in both enzymes- far in which the active-site zinc ligands differ somewhat from His-69, Glu-72, and His-196-and a H20 molecule (3, 4). all others studied. The catalytic zinc (Fig. 4) is bound to one His-69 (L1) and Glu-72 (L2) are separated by 2 amino acid histidine and two cysteine residues; Cys-46 (L1) is separated residues, henceforth referred to as the "short spacer," and from His-67 (L2) by a 19-amino acid segment, constituting the Glu-72 and His-196 (L3) are separated by 123 amino acid short spacer. This is the only relatively long nearest-neighbor residues, henceforth referred to as the "long spacer." These short spacer distance of L1 and L2 in any one of these zinc residues are completely conserved for six carboxypeptidase enzymes.
Load more

Recommended publications
  • Recent Advances in Titanium Radical Redox Catalysis
    JOCSynopsis Cite This: J. Org. Chem. 2019, 84, 14369−14380 pubs.acs.org/joc Recent Advances in Titanium Radical Redox Catalysis Terry McCallum, Xiangyu Wu, and Song Lin* Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States ABSTRACT: New catalytic strategies that leverage single-electron redox events have provided chemists with useful tools for solving synthetic problems. In this context, Ti offers opportunities that are complementary to late transition metals for reaction discovery. Following foundational work on epoxide reductive functionalization, recent methodological advances have significantly expanded the repertoire of Ti radical chemistry. This Synopsis summarizes recent developments in the burgeoning area of Ti radical catalysis with a focus on innovative catalytic strategies such as radical redox-relay and dual catalysis. 1. INTRODUCTION a green chemistry perspective, the abundance and low toxicity of Ti make its complexes highly attractive as reagents and Radical-based chemistry has long been a cornerstone of 5 1 catalysts in organic synthesis. synthetic organic chemistry. The high reactivity of organic IV/III radicals has made possible myriad new reactions that cannot be A classic example of Ti -mediated reactivity is the reductive ring opening of epoxides. This process preferentially readily achieved using two-electron chemistry. However, the − high reactivity of organic radicals is a double-edged sword, as cleaves and functionalizes the more substituted C O bond, the selectivity of these fleeting intermediates can be difficult to providing complementary regioselectivity to Lewis acid control in the presence of multiple chemotypes. In addition, promoted epoxide reactions. The synthetic value of Ti redox catalysis has been highlighted by their many uses in total catalyst-controlled regio- and stereoselective reactions involv- 6−10 ing free-radical intermediates remain limited,2 and the synthesis (Scheme 1).
    [Show full text]
  • Asymmetric Lewis Acid Catalysis Directed by Octahedral Rhodium Centrochirality† Cite This: Chem
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue Asymmetric Lewis acid catalysis directed by octahedral rhodium centrochirality† Cite this: Chem. Sci.,2015,6,1094 Chuanyong Wang,‡a Liang-An Chen,‡b Haohua Huo,a Xiaodong Shen,a Klaus Harms,a Lei Gongb and Eric Meggers*ab A rhodium-based asymmetric catalyst is introduced which derives its optical activity from octahedral centrochirality. Besides providing the exclusive source of chirality, the rhodium center serves as a Lewis acid by activating 2-acyl imidazoles through two point binding and enabling a very effective asymmetric induction mediated by the propeller-like C2-symmetrical ligand sphere. Applications to asymmetric Michael additions (electrophile activation) as well as asymmetric a-aminations (nucleophile activation) Received 9th October 2014 are disclosed, for which the rhodium catalyst is found to be overall superior to its iridium congener. Due Accepted 7th November 2014 to its straightforward proline-mediated synthesis, high catalytic activity (catalyst loadings down to 0.1 DOI: 10.1039/c4sc03101f mol%), and tolerance towards moisture and air, this novel class of chiral-at-rhodium catalysts will likely www.rsc.org/chemicalscience to become of widespread use as chiral Lewis acid catalysts for a large variety of asymmetric transformations. Creative Commons Attribution 3.0 Unported Licence. Lewis acids are capable of activating a large variety of carbon- now wish to report for the rst time that rhodium can also serve heteroatom and carbon–carbon bond forming reactions and as the combined source of centrochirality and Lewis acidity in chiral Lewis acids have therefore become indispensable tools substitutionally labile octahedral metal complexes.
    [Show full text]
  • Research in the Department of Homogeneous Catalysis
    Homogeneous Catalysis – Overview Research in the Department of Homogeneous Catalysis Researchers in our department continue focusing on the development of new catalysis concepts within the areas of organocatalysis and transition metal catalysis. We explore new catalysts, expand the substrate scope of certain catalytic reactions, apply asymmetric catalysis in natural product and pharmaceutical synthesis, and study mechanisms of homogenous catalytic reactions (B. List, K.-R. Pörschke, M. Klußmann, N. Maulide). Since leadership of the department of homogenous catalysis was taken over by Professor Benjamin List in 2005, it has grown significantly from ca. 15 members to currently > 50 members, including the groups of Professor K.-R. Pörschke, who has been a group leader at the institute since two decades now, Dr. M. Klußmann (group leader since 2007), and now also of Dr. N. Maulide, who has joined the department in 2009. The group of Professor List primarily advances enantioselective organocatalysis as a fundamental approach complementing the already more advanced fields of biocatalysis and transition metal catalysis. The List group has a profound interest in developing “new reactions”, designs and identifies new principles for the development of organocatalysts, expands the scope of already developed catalysts such as proline, uses organocatalysis in the synthesis of natural products and pharmaceuticals, and also investigates the mechanism by which organocatalysts activate their substrates. Furthermore, in 2005 the group has first conceptualized and then significantly advanced another approach to asymmetric catalysis, asymmetric counteranion directed catalysis (ACDC). Initially, merely an idea, this approach has progressed within the department but now also at other institutions around the globe, into a truly general strategy for asymmetric synthesis and has found utility in organocatalysis but also in transition metal catalysis and Lewis acid catalysis.
    [Show full text]
  • L. Lewis Acid Catalysis
    L. LEWIS ACID CATALYSIS Background Twenty amino acids is not enough. The breadth of chemistry handled by enzymes requires that additional chemical species be employed in catalysis. So-called cofactors are non-amino acid components of enzymes that may be either associated or bonded to proteins and contribute to rate acceleration. Roughly one-third of all enzymes studied to date employ metal ion cofactors. Metal cations can play one of two roles; they may act as Lewis acids or as redox reagents. As Lewis acids, they function in a role similar to general acids, stabilizing negative charge in the enzyme active site. This chapter will focus on Lewis acid catalysis in reactions that employ water as a nucleophile. Lewis acid catalysis can be observed to play a role in either (a) activating water as a nucleophile or (b) activating the electrophile for nucleophilic attack. Activation of Water as a Nucleophile As noted earlier, water is a poor nucleophile due to the build up of positive charge on the oxygen that accompanies attack upon an electrophile. General base catalysis overcomes that issue by promoting deprotonation of the water molecule as it attacks. Another approach is to stabilize the hydroxide ion within the enzyme active site. While the metal ion itself is a Lewis acid (electron pair acceptor), the hydrated metal ion is a Bronsted acid (a proton donor) according to Equation L.1. n+ (n-1)+ + M(H2O)6 ⇔ M(H2O)5(OH) + H Eq L.1 In this instance Lewis acidity and Bronsted acidity are linked. The capacity of the metal cation to stabilize negative charge from a hydroxide (hydroxo in inorganic-speak) ligand is a reflection of the Lewis acidity of the cation.
    [Show full text]
  • Bulky Aluminum Lewis Acids As Novel Efficient and Chemoselective
    Erschienen in: Synlett ; 1999 (1999), 5. - S. 584-586 https://dx.doi.org/10.1055/s-1999-2667 584 Bulky Aluminum Lewis Acids as Novel Efficient and Chemoselective Catalysts for the Allylation of Aldehydes Andreas Marx, Hisashi Yamamoto* Graduate School of Engineering, Nagoya University, CREST, Chikusa, Nagoya 464-8603, Japan Fax +81(52)789-3222; E-mail: [email protected] position of the bulky phenol ligands resulted in further ac- Abstract: Bulky aluminum Lewis acids such as MAD and MABR celeration of the rate. Thus, methylaluminum bis(4-bro- are introduced as new efficient catalysts in substoichiometric 8,9 amounts for the allylation of aldehydes with allyltributylstannane. mo-2,6-di-tert-butyl-phenoxide) (MABR) performed In addition, chemoselective allylation of a less hindered or aromatic the reaction between 1 and 2 to yield the desired product aldehyde was achieved with catalytic amounts of the carbonyl re- 3 in excellent yield (93%) within 1 h at -20 °C (Table 1, ceptor aluminum tris(2,6-diphenyl-phenoxide) (ATPH). Entry 5). It turned out that MABR is the reagent of choice Keywords: allylation, allyltributylstannane, Lewis acid catalysis, for the catalytic allylation of aldehydes with allyltributyl- MABR, ATPH stannane. It is noteworthy that aluminum tris(2,6-diphe- nylphenoxide) (ATPH)8,9 which is known to complex carbonyl functionalities very tightly due to its bowl-like The Lewis acid promoted allylation of aldehydes using shape11 is capable of promoting catalytic allylation of ben- allystannanes or their less reactive counterparts allylsi- zaldehyde as well (Table 1, Entry 6). Bulkiness of the phe- lanes is a versatile synthetic tool.1 Numerous Lewis acids noxide ligands in the organoaluminum Lewis acids seems ◊ to be a prerequisite for catalytic activity and efficiency.
    [Show full text]
  • Lecture 13 Electrophilic Aromatic Substitution I 5.1 Principles
    NPTEL – Chemistry – Principles of Organic Synthesis Lecture 13 Electrophilic Aromatic Substitution I 5.1 Principles The reaction occurs in two stages: the electrophile adds to one carbon atom of the aromatic ring, yielding a carbocation in which the positive charge is delocalized, and a proton is then eliminated from the adduct. H E H E H E E -H E 5.2 Formation of Carbon-Carbon Bonds 5.2.1 Friedel-Crafts Acylation Acylation of aromatic rings is generally peroformed using acid chloride or acid anhydride as an acylating agent in the presence of Lewis acid. O Z RCOCl, AlCl Z 3 R H2O Mechanism AlCl3 RCOCl RC=O + AlCl4 H H RC=O COR Z Z COR Z Joint initiative of IITs and IISc – Funded by MHRD Page 1 of 26 NPTEL – Chemistry – Principles of Organic Synthesis In some circumstances, carboxylic acid is used as an acylating agent in the presence of a proton acid. HO OH O 2 PhOH, H2SO4 O O -H2O O O Phenolphthalein Indicator Intramolecular reactions are of particular value to construct cyclic systems. These reactions are usually carried out using dibasic acid anhydrides. For example, the synthesis -tetralone has been accomplished from benzene and succinic anhydride using AlCl3 in 80% yield. O O OH OH AlCl3 reduction + O O O O SOCl2 Cl AlCl3 O O Joint initiative of IITs and IISc – Funded by MHRD Page 2 of 26 NPTEL – Chemistry – Principles of Organic Synthesis Examples: 5 mol% Tb(OTf)3 CO H 2 PhCl O D.-M. Cui, C. Zhang, M. Kawamura, S.
    [Show full text]
  • Template for Electronic Submission to ACS Journals
    Max-Planck-Institut für Kohlenforschung Journal Article published in: J. Am. Chem. Soc., 2018, 140, 12671–12676, ACS Publications https://doi.org/10.1021/jacs.8b07092 This article may be used for non-commercial purposes. Scalable and Highly Diastereo- and Enantioselective Catalytic Diels−Alder Reaction of α,β-Unsaturated Methyl Esters Tim Gatzenmeier, Mathias Turberg, Diana Yepes, Youwei Xie, Frank Neese, Giovanni Bistoni and Benjamin List* Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany *Correspondence to: [email protected] ABSTRACT: Despite tremendous advances in enantiose- unsaturated N-acyl oxazolidinones, aldehydes, ketones, lective catalysis of the Diels–Alder reaction, the use of sim- and trifluoroethyl esters as dienophiles. Also some simple, ple α,β-unsaturated esters, one of the most abundant and unactivated α,β-unsaturated esters, such as methyl or ethyl useful class of dienophiles, is still severely limited in scope acrylate and crotonate, in combination with cyclopentadiene due to their low reactivity. We report here a catalytic asym- can engage in highly enantioselective Diels–Alder reactions metric Diels–Alder methodology for a large variety of α,β- catalyzed either by chiral alkyldichloroboranes introduced unsaturated methyl esters and different dienes based on by Hawkins6 or Corey’s cationic oxazaborolidines (CBS),5c,7 extremely reactive silylium imidodiphosphorimidate (IDPi) which undoubtedly represent the most versatile family of Lewis acids. Mechanistic insights from accurate domain- chiral Lewis acids to date. In addition, various organocata- based local pair natural orbital coupled-cluster (DLPNO- lytic approaches have been described for α,β-unsaturated CCSD(T)) calculations rationalize the catalyst control and aldehydes and ketones via asymmetric iminium ion or stereochemical outcome.
    [Show full text]
  • Studies of the Catalytic Activity of Iron (III) Porphyrins for the Protection of Carbonyl Groups in Homogeneous Media
    catalysts Article Studies of the Catalytic Activity of Iron (III) Porphyrins for the Protection of Carbonyl Groups in Homogeneous Media Gabriel Kaetan Baio Ferreira, Charles Carvalho and Shirley Nakagaki * Laboratório de Bioinorgânica e Catálise, Departamento de Química—Centro Politécnico, Universidade Federal do Paraná (UFPR), Curitiba PR 81531980, Brazil; [email protected] (G.K.B.F.); [email protected] (C.C.) * Correspondence: [email protected]; Tel.: +55-41-3361-3180 Received: 8 March 2019; Accepted: 31 March 2019; Published: 4 April 2019 Abstract: The protection of carbonyl groups that produce acetal products is a key reaction in fine chemistry due to the high reactivity of aldehydes and ketones in certain media. This process can be catalyzed by protic or Lewis acids. Since metalloporphyrins often possess free axial positions in the central metal, they can be applied as Lewis acid catalysts, allowing the additional coordination of substrates. Therefore, three ferric complexes were selected to be evaluated as catalysts for the acetalization of benzaldehyde with ethanol and triethyl orthoformate (TEOF) in the homogeneous phase: (i) 5,10,15,20-tetrakis(phenylporphyrin) iron (III) chloride (Fe0F); (ii) 5,10,15,20-tetrakis(2,6-difluorphenylporphyrin) iron (III) chloride (Fe2F); and (iii) 5,10,15,20-tetrakis (pentafluorphenylporphyrin) iron (III) chloride (Fe5F). The complex Fe5F showed the highest catalytic activity, and kinetic parameters were evaluated for this reaction, exhibiting an increasing rate of reaction of about 550-fold in comparison with the non-catalyzed reaction. The reaction scope was also investigated, and Fe5F was found to be active for the acetalization of benzaldehyde and acetophenone, with different protective agents such as alcohols, glycols, glycerol, and epoxide being selective for the formation of cyclic acetals.
    [Show full text]
  • New Conceptual Understanding of Lewis Acidity, Coordinate Covalent Bonding, and Catalysis Joshua A
    Duquesne University Duquesne Scholarship Collection Electronic Theses and Dissertations Summer 2009 New Conceptual Understanding of Lewis Acidity, Coordinate Covalent Bonding, and Catalysis Joshua A. Plumley Follow this and additional works at: https://dsc.duq.edu/etd Recommended Citation Plumley, J. (2009). New Conceptual Understanding of Lewis Acidity, Coordinate Covalent Bonding, and Catalysis (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1052 This Immediate Access is brought to you for free and open access by Duquesne Scholarship Collection. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Duquesne Scholarship Collection. For more information, please contact [email protected]. NEW CONCEPTUAL UNDERSTANDING OF LEWIS ACIDITY, COORDINATE COVALENT BONDING, AND CATALYSIS A Dissertation Submitted to the Bayer School of Natural and Environmental Sciences Duquesne University In partial fulfillment of the requirements for the degree of Doctor of Philosophy By Joshua A. Plumley August 2009 NEW CONCEPTUAL UNDERSTANDING OF LEWIS ACIDITY, COORDINATE COVALENT BONDING, AND CATALYSIS By Joshua A. Plumley Approved August 2009 __________________________________ __________________________________ Jeffrey D. Evanseck Ellen Gawalt Professor of Chemistry and Biochemistry Assistant Professor of Chemistry and Dissertation Director Biochemistry Committee Member Committee Member __________________________________ __________________________________ Douglas J. Fox
    [Show full text]
  • Novel Lewis Acidic Zeolites As Heterogeneous Catalysts for Liquid Phase Chemistry
    Novel Lewis acidic zeolites as heterogeneous catalysts for liquid phase chemistry By Abbas Al-Nayili Submitted to the Department of Chemistry In Partial Fulfilment of the Requirements for the Degree of Doctor Philosophy in Chemistry at the Cardiff Catalysis Institute (CCI) Supervisor: Dr. CERI HAMMOND 2017 Declaration This work has not been submitted in substance for any other degree or award at ths or any other university or place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed …………………………… (candidate) Date …………………..... Statement 1 This thesis is being submitted in partial fulfilment of the requirements for the degre of ……PhD……….. (insert MCh, MD, MPhil, PhD, etc, as appropriate). Signed …………………………… (candidate) Date …………………..... Statement 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the thesis has not been edited by a third party beyond what is permitted by Cardiff University’s Policy on the Use of Third Party Editors by Research Degree Students. Other sources are acknowledged by explicit references. The views expressed are my own. Signed …………………………… (candidate) Date …………………..... Statement 3 I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter -library loan, and for the title and summary to be made available to outside organisations. Signed …………………………… (candidate) Date …………………..... Statement 4: Previously Approved Bar on Access. I hereby give consent for my thesis, if accepted, to be available online in the Univers ity’s Open Access repository and for inter -library loans after expiry of a bar on access previously approved by the Academic Standards and Quality Committee.
    [Show full text]
  • Cornerstone Works for Catalytic 1,3-Dipolar Cycloaddition Reactions
    HETEROCYCLES, Vol. 82, No. 1, 2010 87 HETEROCYCLES, Vol. 82, No. 1, 2010, pp. 87 - 200. © The Japan Institute of Heterocyclic Chemistry Received, 27th January, 2010, Accepted, 3rd August, 2010, Published online, 10th August, 2010 DOI: 10.3987/REV-10-666 CORNERSTONE WORKS FOR CATALYTIC 1,3-DIPOLAR CYCLOADDITION REACTIONS Shuji Kanemasa* Institute for Materials Chemistry and Engineering, Advanced Education in Utilization of Fossil Resources, Kyushu University, 6-1 Kasugakoen, Kasuga 816-8580, [email protected]) Abstract – This review covers the following subjects: (1) The chemistry of N-metalated azomethine ylide as a new 1,3-dipole containing a metal atom is studied. This 1,3-dipole, generated from (N-alkylideneamino)alkanoates upon treatment with a Lewis acid and amine base, undergoes rapid 1,3-dipolar cyclo- additions toward electron-deficient alkenes. Especially, !,"-unsaturated carbonyl substrates show high rate acceleration to give pyrrolidine-2,4-dicarboxylates in a highly regio- and endo-selective manner. (2) This 1,3-dipolar cycloaddition reaction of (N-alkylideneamino)acetate can be switched into anti-selective Michael addition reaction by modification of substrate structures as well as reaction conditions. (3) Two types of heterocyclic chiral auxiliaries are demonstrated for the asymmetric 1,3-dipolar cycloadditions. One types are attached at the "-position of !,"-unsaturated esters. The resulting chiral !,"-unsaturated esters are successfully applied to the stereoselective asymmetric cycloadditions of N-metalated azomethine ylides. The other types include 4-benzyl-2,2,5,5-tetramethyloxazolidine-3-acrylamides which are based on the conformational control of the acrylamide reaction site and that of steric shielding of 4-benzyl amoiety.
    [Show full text]
  • Asymmetric Catalysis in Aqueous Media*
    Pure Appl. Chem., Vol. 79, No. 2, pp. 235–245, 2007. doi:10.1351/pac200779020235 © 2007 IUPAC Asymmetric catalysis in aqueous media* Shu– Kobayashi Graduate School of Pharmaceutical Sciences, The University of Tokyo, The HFRE Division, ERATO, Japan Science and Technology Agency (JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Abstract: Lewis acid catalysis has attracted much attention in organic synthesis because of unique reactivity and selectivity attained under mild conditions. Although various kinds of Lewis acids have been developed and applied in industry, these Lewis acids must be gener- ally used under strictly anhydrous conditions. The presence of even a small amount of water handles the reactions owing to preferential reactions of the Lewis acids with water rather than the substrates. In contrast, rare earth and other metal complexes have been found to be water- compatible. Several catalytic asymmetric reactions in aqueous media, including hydroxy- methylation of silicon enolates with an aqueous solution of formaldehyde in the presence of Sc(OTf)3–chiral bipyridine ligand or Bi(OTf)3–chiral bipyridine ligand, Sc- or Bi-catalyzed asymmetric meso-epoxide ring-opening reactions with amines, and asymmetric Mannich- type reactions of silicon enolates with N-acylhydrazones in the presence of a chiral Zn cata- lyst have been developed. Water plays key roles in these asymmetric reactions. Keywords: reactions in aqueous media; Lewis acids; catalytic asymmetric reactions; hydroxymethylation of silicon enolates; Sc(OTf)3–chiral bipyridine ligand. INTRODUCTION Organic reactions in aqueous media are of current interest owing to the key role played by water as a solvent for green chemistry [1].
    [Show full text]