Physico-Chemical Characterization And

Ionic LiquidLiquid----SupportedSupported Schiff Bases and their Transition Metal Complexes: Synthesis, PhysicoPhysico----ChemicalChemical Characterization and Biological Activities

A Thesis submitted to the UNIVERSITY OF NORTH BENGAL

For the Award of

DOCTOR OF PHILOSOPHY ininin CHEMISTRY

ByByBy Mr. SANJOY SAHA M.Sc. in Chemistry

Supervisor DR. BISWAJIT SINHA DEPARTMENT OF CHEMISTRY UNIVERSITY OF NORTH BENGAL OCTOBER-2018

Dedicated To My Beloved Parents

Abstract

Chapter I contains a brief overview on the ionic liquids (ILs), specially functionalized ionic liquids (FILs) along with the properties of the ionic liquids consisting of different cations and anions, their applications and the advantages of using ILs over conventional organic solvents. Chemistry of Schiff bases and their transition metal complexes as well as their applications in different fields were also briefly discussed. This chapter also contains a brief literature survey on related works as well as the object and application of the research works embodied in this dissertation. Chapter II briefly describes the spectroscopic and analytical techniques employed for the physico-chemical characterization of the synthesized compounds. This chapter also contains sources of the different chemicals used and describes the syntheses and physicochemical characterization of some amine functionalized ionic liquids required for the syntheses of various ionic liquid-supported Schiff bases used as ligands in subsequent chapters of this thesis. In chapter III Mn(II) and Co(II) complexes synthesized from the ionic liquid- supported Schiff base, 1-{2-(2-hydroxybenzylideneamino)ethyl}-3-methyl imidazolium bromide have been presented. Their structural characterization by various analytical and spectroscopic methods was described. Their antibacterial activities were tested by in vitro disc diffusion method against Escherichia coli and Bacillus subtilis to assess their minimum inhibition concentrations. Chapter IV describes syntheses of the ionic liquid supported Schiff base, 1-{2- [(2-hydroxybenzylidene)amino]ethyl}-3-methylimidazolium hexafluorophosphate and its Mn(II), Co(II) and Cu(II) complexes. Their physico-chemical characterizations by various spectroscopic (ESI-MS, 1H-NMR, 13 C-NMR, FT-IR and UV-Visible) and analytical (elemental analysis and magnetic susceptibility measurements) techniques were presented. Antibacterial activities against gram positive and negative bacteria by in vitro disc diffusion methods have been discussed. In chapter V, the syntheses of an air and moisture stable ionic liquid- supported Schiff base, 1-{2-(2-hydroxy-5-nitrobenzylideneamino)ethyl}-3- ethylimidazolium tetrafluoroborate and its Co(II), Ni(II) and Cu(II) complexes have been described. These compounds were characterized by different spectroscopic

i (powder X-ray diffraction, ESI-MS, UV-Visible, FT-IR, 1 H-NMR and 13 C-NMR) methods and analytical (elemental analysis, molar conductance and magnetic susceptibility measurements) techniques. The antibacterial studies of the synthesized compounds were explored and the metal complexes exhibited significant activities against the selected gram negative bacteria ( Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter aerogenes ) and gram positive bacteria (Staphylococcus aureus and Bacillus cereus ). In Chapter VI the syntheses of the Co(II), Ni(II) and Cu(II) complexes of the Schiff base, 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate have been described. These complexes were characterized by various analytical and spectroscopic methods. The antibacterial activities ( in vitro ) of the Schiff base and its complexes have been performed by disc diffusion method. The complexes showed reasonable antibacterial activities against the selected four gram negative bacteria ( E. coli, P. aeruginosa, P. vulgaris and E. aerogenes ) and two gram positive bacteria ( S. aureus and B. cereus ). Chapter VII describes the syntheses and physico-chemical characterization of the Schiff base, 1-{2-(2-hydroxy-5-bromobenzylideneamino)ethyl}-3- ethylimidazolium tetrafluoborate and its Fe(III) and Cr(III) complexes. Their physico- chemical characterization by various analytical and spectroscopic methods such as elemental analysis, UV-Visible, FT-IR, 1 H NMR, ESI MS, TGA/DTG, molar conductance and magnetic susceptibility measurements have been illustrated. Antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were also perfomed. Chapter VIII describes the synthesis, physico-chemical characterization and potential biological applications of some transition metal complexes of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy-5-chloro-benzylideneamino)ethyl}-3- methylimidazolium tetrafluoroborate. The geometrical structures of the complexes were established by different spectroscopic and analytical data. Their potential biological applications against gram positive ( Staphylococcus aureus and Bacillus cereus ) and gram negative ( Escherichia coli and Klebsiella pneumoniae ) bacteria were explored and discussed accordingly. Finally in chapter IX the concluding remarks on the research works embodied in this thesis were made.

ii PREFACE

I started the research work presented in this thesis entitled “ Ionic Liquid-Supported Schiff Bases and their Transition Metal Complexes: Synthesis, Physico-Chemical Characterization and Biological Activities ” in 2011 under the supervision of Dr. Biswajit Sinha, Professor, Department of Chemistry, University of North Bengal, India with an aim to synthesize the imidazolium based ionic liquid-supported Schiff bases and their transition metal complexes, their physico-chemical characterization and exploration of their biological activities, specially antibacterial and antimicrobial activities against naturally available bacteria. It is well known that metal ions play vital roles in a number of biological processes. The metal ions with biologically active ligands are a subject of considerable interest; therefore much attention was paid due to their numerous applications as antitumor, antibacterial and antifungal agents. Schiff bases have been studied extensively over the years due to their selectivity and sensitivity towards various transition metal ions. They may act as polydentate ligands for the complexation with different transition metal ions like Mn(II), Co(II), Ni(II), Cu(II), Mn(III), Fe(III), Cr(III), etc . Of late ionic liquids have drawn much interest in the context of green synthesis and catalysis, etc . Their merit lies in the ease with which their properties can be tuned by varying either the anion or the cation or the substitutions on the cation. The study of ionic liquids that are air and moisture stable has become a subject of extensive scientific investigations well documented in the literature. Catalytic utilization of the transition metal complexes prepared by these tunable ligands is very promising. Suitable changes of the steric or electronic environment about the metal complexes can have a dramatic influence on their physico-chemical properties. The functionalized ionic liquids (FILs) are favorite as ligands for the recovery of metal catalysts used in a series of chemical transformations such as olefin metathesis, hydrogenation, hydroformylation, Negishi cross-coupling reaction, Heck reaction, Suzuki and Stille coupling reactions, etc . Therefore studies on the ionic liquid (imidazolium based)-supported Schiff bases and their transition metal complexes would be quite interesting from the point of view: their stability, geometry, biological activity and potential applications in many fields.

iii Acknowledgement Words fall short to express my sincere gratitude and indebtedness to my supervisor, Dr. Biswajit Sinha, Professor, Department of Chemistry, University of North Bengal for his untiring guidance and valuable suggestions during the course of research work. His support and valuable suggestions were truly incomparable, encouraging and motivational. I am profoundly obliged to Prof. P. Ghosh, HEAD, Department of Chemistry, N.B.U and Prof. M. N. Roy, Coordinator, SAP-DRS-III, N.B.U for their constant touch, constructive criticism and valuable advices during the period of my research work. I also wish to express my deep sense of gratitude to the other faculty members of the Department of Chemistry, N.B.U for their cordial support. I am also thankful to all the non-teaching staff of this department for their helps. I sincerely thank my lab mates Dr. Dhiraj Brahmin, Dr. Abhijit Sarkar, Dr. Rajendra Pradhan, Mr. Bijan Kumar Pandit, Mr. Amarjit Kamath, Mr. Koushik Acharjee, Mr. Dipu Kumar Mishra, Mrs. Annaya Das and Mr. Uttam Kumar Singha for their helping hands during different stages of my research work in spite of their busy academic schedule and involvements. I am highly grateful to my colleagues especially Dr. R.P. Dhakal, Principal, Kalimpong College, Kalimpong for helping me in some or the other way. Special thanks are due to Dr. Malay Bhattachariya, Department of Tea Science, N.B.U & Sri. Goutam Basak, Raiganj University for their help and cordial cooperation. I also acknowledge the services of USIC (NBU), SAIF-NEHU (SHILONG), CDRI, (Lucknow), IIT (Chennai) in accomplishing various analytical and spectroscopic analyses. I am highly obliged to the Departmental Special Assistance Scheme under the University Grants Commission, New Delhi, India (SAP-DRS-III, NO.540/12/DRS/2013) for providing financial and instrumental assistance. Love and moral support from my parents (Mr. Bimal Chandra Saha & Mrs. Maya Saha), brothers (Tapabijoy Saha and Prasunjoy Saha) and my beloved wife (Srijani Saha) at critical junctures made me overcome all the hurdles and especially the effortless smiles of my beautiful daughter Arshia Saha enabled me to complete this thesis. Finally, I must thank the almighty God, without whose poise the whole episode could have had condensed to nothing.

Sanjoy Saha Department of Chemistry University of North Bengal Darjeeling-734013, West Bengal, India

TABLE OF CONTENTS

Topic Page No.

Abstract i-ii

Preface iii

Acknowledgement iv

Table of Contents v-x

List of Tables xi-xi

List of Figures xii-xviii

List of Schemes xix-xix

List of Appendices xx-xx

List of Abbreviation xxi-xxiv

CHAPTER I: General Introduction 1-27

Introduction 1-1

1.1 . Ionic liquids 1-4

1.2. Functionalized ionic liquids 4-7

1.2.1. Functionalized cations 4-5

1.2.2. Functionalized anions 6-6

1.3. Schiff base 7-11

1.4 . Transition Metal Complexes of Schiff Bases 11-13

1.5 . Literature Review 13-18

1.6. Object and Application of the Research work 19-19

References 20-27

CHAPTER II: Experimental Section 28-52

2.1. Materials 28-29

2. 2. Experimental Methods 29-41

2.1.1. Physico-chemical methods used to characterize synthesized compounds 29-35

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Topic Page No.

2.2.2. Mass measurements 35-36

2.2.3. Antibacterial assay 36-41

2.2.3.1. Gram negative bacteria 37-39

2.2.3.2. Gram positive bacteria 40-41

2.2.4. Synthesis of functionalized ionic liquids (FILs) 41-52

2.2.4.1. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium bromide, 41-44 [2-aemim][Br (1a )

2.2.4.2. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium 44-46 hexafluorophosphate, [2-aemim]PF 6 (1b )

2.2.4.3. Synthesis of 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, 46-49 [2-aeeim]BF 4 (1c )

2.2.4.4. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium 50-52 tetrafluoroborate, [2-aemim]BF 4 (1d )

References 52-52 CHAPTER III: Synthesis, characterization and antibacterial studies of Mn(II) and Co(II) complexes of an ionic liquid supported Schiff base: 53-67 [1-{2-(2-hydroxybenzylideneamino)ethyl}-3-methylimidazolium] bromide 3.1. Introduction 53-54

3.2. Experimental section 54-56

3.2.1. Materials and methods 54-55

3.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2a ) 55-55

3.2.3. Synthesis of the metal complexes ( 3a and 4 a) 55-56

3.3. Results and Discussion 57-65

3.3.1. FT-IR spectral studies 57-59

3.3.2. Mass spectral studies 59-61

3.3.3. 1H and 13 C-NMR spectral studies 61-63

3.3.4. Molar conductance measurements 62-62

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Topic Page No.

3.3.5. Electronic absorption spectral and magnetic moment studies 63-64

3.3.6. Antibacterial activities 64-65

4.4. Conclusion 65-65

References 66-67

CHAPTER IV: Mn(II), Co(II) and Cu(II) complexes of an ionic liquid- supported Schiff base, [1-{2-(2-hydroxybenzylideneamino)ethyl}-3-methyl 68-85 imidazolium]PF 6: Synthesis, Physico-chemical characterization and biological activities

4.1. Introduction 68-69

4.2. Experimental section 69-72

4.2.1. Materials and methods 69-70

4.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2b ) 70-70

4.2.3. Synthesis of metal complexes ( 3b , 4b and 5b ) 70-72

4.2.4. Antibacterial Activity 72-72

4.3. Results and Discussion 72-82

4.3.1. FT-IR spectral studies 72-75

4.3.2. Mass spectral studies 75-77

4.3.3. 1H and 13 C-NMR spectral studies 78-79

4.3.4. Electronic absorption spectral and magnetic moment studies 79-80

4.3.5. Antibacterial activities 80-82

4.4. Conclusion 82-82

Reference 83-85 CHAPTER V: Synthesis, structural characterization and exploration of antibacterial activities of Co(II), Ni(II) and Cu(II) complexes derived 86-105 from an ionic liquid-supported Schiff base: 1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethylimidazolium tetrafluoroborate 5.1. Introduction 86-87

5.2. Experimental section 87-90

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Topic Page No.

5.2.1. Materials and methods 87-88

5.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH ( 2c ) 88-88

5.2.3. Synthesis of the metal complexes ( 3c , 4c and 5c ) 88-90

5.2.4. Antibacterial assay 90-90

5.3. Results and Discussion 90-103

5.3.1. FT-IR spectral studies 90-93

5.3.2. Mass spectral studies 93-95

5.3.3. 1H and 13 C-NMR spectral studies 96-97

5.3.4. Powder X-ray diffraction analysis 97-99

5.3.5. Molar conductance measurements 100-100

5.3.6. Electronic absorption spectral and magnetic moment studies 100-101

5.3.7. Antibacterial activities 101-103

5.4. Conclusion 103-104

References 104-105 CHAPTER VI: Physico-chemical characterization and biological studies of newly synthesized metal complexes of an Ionic liquid-supported Schiff base: 106-123 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate 6.1. Introduction 106-107

6.2. Experimental section 107-110

6.2.1. Materials and Methods 107-108

6.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH ( 2d ) 108-108

6.2.3. Synthesis of the metal complexes ( 3d, 4d and 5d ) 108-110

6.2.4. Antibacterial assay 110-110

6.3. Results and Discussion 110-120

6.3.1. FT-IR spectral studies 110-113

6.3.2. Mass spectral studies 113-115 Contd….

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6.3.3. 1H and 13 C-NMR spectral studies 116-117

6.3.4. Molar conductance measurements 117-117

6.3.5. Electronic absorption spectral and magnetic moment studies 117-118

6.3.6. Antibacterial activities 118-120

6.4. Conclusion 120-121

References 121-123

CHAPTER VII: Synthesis, Physico-chemical Characterization and Antibacterial studies of Fe(III) and Cr(III) complexes with an Ionic 124-138 Liquid-supported Schiff base ligand 7.1. Introduction 124-125

7.2. Experimental section 125-128

7.2.1. Materials and Methods 125-126

7.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH ( 2d ) 126-126

7.3.3. Synthesis of the metal complexes ( 6d and 7d ) 127-128

7.3. Results and Discussion 129-136

7.3.1. FT-IR spectra 129-131

7.3.2. Mass spectra 131-132

7.3.3. 1H-NMR and 13 C-NMR spectra 132-132

7.3.4. Molar Conductance measurements 132-133

7.3.5. Electronic spectra and magnetic moment studies 133-133

7.3.6. Thermal analysis 134-134

7.3.7. Antibacterial studies 134-136

7.4 . Conclusion 136-136

References 136-138

Contd…

Topic Page No. CHAPTER VIII: Synthesis, Physico-chemical characterization and potential biological applications of Transition metal complexes obtained from an ionic liquid-supported Schiff base ligand: 1-{2-(2-hydroxy-5- 139-166 chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate

8.1. Introduction 139-140

8.2. Experimental section 140-147

8.2.1. Material and methods 140-141

8.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH ( 2e ) 141-141

8.2.3. Synthesis of the metal complexes ( 3e , 4e and 5e ) 142-144

8.2.4. Synthesis of the metal complexes ( 6e , 7e and 8e ) 144-147

8.2.5. Antimicrobial activity 147-147

8.3. Results and Discussion 147-163

8.3.1. FT-IR spectral studies 148-151

8.3.2. 1H and 13 C-NMR spectral studies 151-153

8.3.3. Powder X-ray diffraction analysis 153-156

8.3.4. Mass spectral studies 156-160

8.3.5. Electronic absorption spectra and magnetic moment studies 161-162

8.3.6. Antimicrobial activities 162-163

8.4. Conclusion 164-164

References 164-166

CHAPTER IX: Concluding Remarks 167-169

APPENDIX I 170-170

APPENDIX II 171-171

APPENDIX III 172-172

APPENDIX IV 173-174

BIBLIOGRAPHY 174-186

INDEX 187-190

LIST OF TABLES Table Page No.

2.1. List of reagents and solvents. 28-39

4.1. Antibacterial assay data of Schiff base ( 2b ) and its metal complexes 81-81 (3b , 4b and 5b ) against Escherichia Coli .

4.2. Antibacterial assay data of Schiff base ( 2b ) and its metal complexes ( 3b , 4b 81-81 and 5b ) against bacterial strains Bacillus subtilis .

5.1. Antibacterial activity data of Schiff base ( 2c ) and its metal complexes 102-102 (3c , 4c and 5c ) against E. Coli, S. aureus and B.cereus.

5.2. Antibacterial activity data of Schiff base ( 2c ) and its metal complexes 102-102 (3c , 4c and 5c ) against P. Aeruginosa, P. vulgaris and E. Aerogenes.

6.1. Antibacterial activity data of Schiff base ( 2d ) and its metal complexes ( 3d, 119-119 4d and 5d ) against E. Coli, S. aureus and B.cereus .

6.3. Antibacterial activity data of Schiff base ( 2d ) and its metal complexes ( 3d, 4d and 5d ) against P. aeruginosa, P. vulgaris and E. 119-119 aerogenes . 7.1. Biological assays data of 1-{2-(2-hydroxy-5-bromobenzyl amine)ethyl}-3-ethylimidazolium tetrafluoroborate (2d ); Fe(III) complex 135-135 (6d ) and Cr(III) complex ( 7d ).against E. coli and S.aureus. 8.1. Antibacterial activity of the ligand ( 2e ) and its metal complexes ( 3e 163-163 to 8e ).

LIST OF FIGURES

Figure Page No.

1.1. Some of the typical anions and cations used in ionic liquids preparation 2

1.2. Synthesis of imidazolium salt from alkyl halide 3

1.3. Metathesis reaction of imidazolium moiety. 4

1.4 . Synthesis of task specific ionic liquids 5

1.5. Mono-functionalized imidazolium cations and their potential applications. 5

1.6. Functionalized anions and their potential applications. 6

1.7. Synthesis of Schiff base from amine and carbonyl precursor. 8

1.8. Schiff bases with mono-, bi-, tri- and tetra donor atoms. 9

1.9. Synthesis of Ionic liquid-supported Schiff bases. 10

1.10. Keto-enol tautomerism of IL-supported Schiff base. 10

1.11. Extraction of Ni 2+ ion from aqueous solution. 11

1.12. Synthesis of Ionic liquid-supported Pd(II) complex. 13

1.13. Synthesis of TSIL. 14

1.14. Synthesis of TSIL using Michael reaction. 15

1.15. Synthesis of amine functionalized ionic liquid. 15

1.16. Synthesis of Cu[EDA-mim] 2 16

1.17. Synthesis of imidazolium dirhodium(II) carboxylate. 17

1.18. Synthesis of the chiral oxovanadium(IV) complex 18

1.19. Synthesis of IL-supported Schiff base 18

2.1. Atomic Absorption Spectrophotometer (Varian SpectrAA 50B) 30

2.2. (Magway MSB Mk1). 31

2.3. Melting point apparatus. 31

2.4. D8 Advanced Bruker. 32

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Topic Page No.

2.5. Perkin-Elmer Spectrum FT-IR spectrometer (RX-1). 33

2.6. Jasco V-530 double beam UV-VIS Spectrophotometer. 33

2.7. FT-NMR (Bruker Avance-II 400 MHz). 34

2.8. Systronic conductivity TDS-308 metre. 34

2.9. JMS-T100LC spectrometer. 35

2.10. 4000 Perkin–Elmer thermal analyzer. 35

2.11. Digital electronic analytical balance (Mettler Toledo, AG 285). 36

2.12. E. coli bacteria. 37

2.13. Pseudomonas aeruginosa bacteria 38

2.14. P. vulgaris bacteria. 38

2.15. Enterobacter aerogenes bacteria. 39

2.16. K. pneumoniae bacteria 39

2.17. B. subtilis bacteria. 40

2.18. B. cereus bacteria. 40

2.19. S. aureus bacteria. 41

2.20. 1-(2-aminoethyl)-3-methyllimidazolium bromide, [2-aemim]Br 42

2.21. FT-IR spectrum of of [2-aemim]Br 42

2.22. 1H NMR spectrum of [2-aemim]Br 43

2.23. 13 C NMR spectrum of [2-aemim]Br 43

2.24. ESI-MS spectrum of [2-aemim]Br 44

2.25. 1-(2-aminoethyl)-3-methyllimidazolium hexafluorophosphate, [2- 45 aeeim]PF 6

2.26. FT-IR spectrum of [2-aemim]PF 6 46

2.27. ESI-MS spectrum of [2-aemim]PF 6 46

2.28. 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2-aeeim]BF 4 47

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Topic Page No.

2.29. FT-IR spectrum of [2-aeeim]BF 4 48

1 2.30. H NMR spectrum of [2-aeeim]BF 4 48

13 2.31. C NMR spectrum of [2-aeeim]BF 4 49

2.32. ESI-MS spectrum of [2-aeeim]BF 4 49

2.33. 1-(2-aminoethyl)-3-methyllimidazolium tetrafluoroborate [2-aemim]BF 4 50

2.34. FT-IR spectrum of [2-aemim]BF 4 51

2.35. ESI-MS spectrum of [2-aemim]BF 4 51

3.1. FT-IR spectrum of LH ( 2a ) 58

3.2. FT-IR spectrum of MnII) complex ( 3a ) 58

3.3. FT-IR spectrum of Co(II) complex ( 4a ) 59

3.4. ESI-MS spectrum of LH (2a ) 60

3.5. ESI-MS spectrum of Mn(II) complex ( 3a ) 60

3.6. ESI-MS spectrum of Co(II) complex ( 4a ) 61

3.7. 1H-NMR spectrum of LH ( 2a ) 62

3.8. 13 C-NMR spectrum of LH ( 2a ) 63

3.9. UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): 64 (A) LH ( 2a ); (B) Mn(II) complex ( 3a ) and (C) Co(II) complex ( 4a ).

3.10. Inhibition zones for anti-bacterial activities: A, LH (2a ); B; the Mn(II) 65 complex ( 3a); C, the Co(II) complex ( 4a ) against Escherichia Coli .

4.1. FT-IR spectrum of LH ( 2b ) 73

4.2. FT-IR spectrum of Mn(II) complex ( 3b ) 74

4.3. FT-IR spectrum of Co(II) complex ( 4b ) 74

4.4. FT-IR spectrum of Cu(II) complex ( 5b ) 75

4.5. ESI-MS spectrum of LH (2b ) 76

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Topic Page No.

4.6. ESI-MS spectrum of Mn(II) complex ( 3b ) 76

4.7. ESI-MS spectrum of Co(II) complex ( 4b ) 77

4.8. ESI-MS spectrum of Cu(II) complex ( 5b ) 77

4.9. 1H-NMR spectrum of LH ( 2b ) 78

4.10. 13 C-NMR spectrum of LH ( 2b ) 79

4.11 .UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M ): (A) LH ( 2b); (B) Mn(II) complex (3b ); (C) Co(II) complex ( 4b ) and (D) Cu(II) 80 complex ( 5b ).

4.12. Inhibition zones for anti-bacterial activities: A, for LH ( 2b ); B, for Mn(II) complex ( 3b ); C, for Co(II) complex ( 4b ); D, for Cu(II) complex ( 5b ) against 82 Escherichia Coli .

5.1. FT-IR spectrum of LH ( 2c ) 94

5.2. FT-IR spectrum of Co(II) complex (3c ) 94

5.3. FT-IR spectrum of Ni(II) complex ( 4c ) 95

5.5. ESI-MS spectrum of Cu(II) complex ( 5c ) 95

5.6. ESI-MS spectrum of Co(II) complex ( 3c ) 94

5.7. ESI-MS spectrum of Ni(II) complex ( 4c ) 95

5.8. ESI-MS spectrum of Cu(II)complex ( 5c ) 95

5.9. 1H-NMR spectrum of LH (2c ) 96

5.10. 13 C-NMR spectrum of LH ( 2c ) 97

5.11. PXRD patterns of LH ( 2c ) 98

5.12. PXRD patterns of Co(II) complex (3c ) 98

5.13. PXRD patterns of Ni(II) complex (4c ) 99

5.14. PXRD patterns of Cu(II) complex (5c ) 99

5.15. UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): (A) LH ( 2c ); (B) Co(II) complex (3c ); (C) Ni(II) complex (4c ) and (D) Cu(II) 101 complex (5c ).

Contd…

Topic Page No.

5.16. Inhibition zones for the LH ( 2c ), Co(II) complex ( 3c ), Ni(II) complex ( 4c ) 103 and Cu(II) complex ( 5c )

6.1. FT-IR spectrum of LH ( 2d ) 111

6.2. FT-IR spectrum of Co(II) complex ( 3d ) 112

6.3. FT-IR spectrum of Ni(II) complex ( 4d ) 112

6.4. FT-IR spectrum of Cu(II) complex ( 5d ) 113

6.5. ESI-MS spectrum of LH (2d ) 114

6.6. ESI-MS spectrum of Co(II) complex ( 3d ) 114

6.7. ESI-MS spectrum of Ni(II) complex ( 4d ) 115

6.8. ESI-MS spectrum of Cu(II) complex ( 5d ) 115

6.9. 1H-NMR spectrum of LH ( 2d ) 116

6.10. 13 C-NMR spectrum of LH ( 2d ) 117

6.11 . UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M ): (A) LH ( 2d ); (B) Co(II) complex ( 3d ); (C) Ni(II) complex ( 4d ) and (D) 118 Cu(II) complex ( 5d )

6.12. Inhibition zones for the LH ( 2d ), Co(II) complex ( 3d ), Ni(II) complex 120 (4d) and Cu(II) complex ( 5d )

7.1. SEM image of Fe(III) complex ( 6d ) 128

7.2. SEM image of Cr(III) complex ( 7d ) 128

7.3. FT-IR spectrum of LH ( 2d ) 130

7.4. FT-IR spectrum of Fe(III) complex ( 6d ) 130

7.5. FT-IR spectrum of Cr(III) complex ( 7d ) 131

7.6. ESI-MS spectrum of Fe(III) complex ( 6d ) 131

7.7. ESI-MS spectrum of Cr(III) complex ( 7d ) 132

7.8. UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): 133 (A) LH ( 2d ); (B) Fe(III) complex ( 6d ) and (C) Cr(III) complex( 7d )

7.9. TGA analysis of Fe(III) complex (6d ) and Cr(III) complex (7d ) 134

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7.10. MIC of the Fe(III) complex ( 6d ) and Cr(III) complex ( 7d ) against S. 136 aureus.

8.1. SEM image of Co(II) complex ( 3e ) 143

8.2. SEM image of Ni(II) complex ( 4e ) 143

8.3. SEM image of Cu(II) complex ( 5e ) 144

8.4. SEM image of Mn(III) complex ( 6e ) 145

8.5. SEM image of Fe(III) complex ( 7e ) 146

8.6. SEM image of Cr(III) complex ( 8e ) 147

8.7. FT-IR spectra of ligand ( 2e ) 148

8.8. FT-IR spectra of Co(II) complex ( 3e ) 149

8.9. FT-IR spectra of Ni(II) complex ( 4e ) 149

8.10. FT-IR spectra of Cu(II) complex ( 5e ) 150

8.11. FT-IR spectra of Mn(III) complex ( 6e ) 150

8.12. FT-IR spectra of Fe(III) complex ( 7e ) 151

8.13. FT-IR spectra of Cr(III) complex ( 8e ) 151

8.14. 1H-NMR spectra of LH (2e ) 152

13 8.15. C-NMR spectra of LH (2e ) 152

8.16. PXRD spectra of LH (2e ) 153

8.17. PXRD spectra of Co(II) complex (3e ) 154

8.18. PXRD spectra of Ni(II)complex (4e ) 154

8.19. PXRD spectra of Cu(II) complex (5e ) 155

8.20. PXRD spectra of Mn(III) complex (6e ) 155

8.21. PXRD spectra of Fe(III) complex (7e ) 156

8.22. PXRD spectra of Cr(III) complex ( 8e ) 156

8.23. ESI-MS spectrum of LH ( 2e ) 157

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Topic Page No.

8.24. ESI-MS spectrum of Co(II)complex ( 3e ) 158

8.25. ESI-MS spectrum of Ni(II)complex ( 4e ) 158

8.26. ESI-MS spectrum of Cu(II)complex ( 5e ) 159

8.27. ESI-MS spectrum of Mn(III)complex ( 6e ) 159

8.28. ESI-MS spectrum of Fe(III)complex ( 7e ) 160

8.29. ESI-MS spectrum of Cr(III)complex ( 8e ) 160

8.30. The UV-Vis spectra of ligand ( 2e ) and its metal complexes ( 3e to 8e ) 162

8.31. MIC of the Cu(II) complex ( 5e ) against K. pneumoniae and B. cereus . 163

xviii

LIST OF SCHEMES

SCHEME Page No. 2.1. Synthesis of [2-aemim][Br] (1a ) 44 2.2. Synthesis of FILs ( 1b ), ( 1c ) and ( 1d ) 52 3.1. Synthesis of the ionic liquid-supported Schiff base, [1-{2-[(2- hydroxybenzylidene)amino]ethyl}-3-methyl-1H imidazolium] bromide 56 (2a ), and its M(II) complexes ( 3a and 4a ) from ( 2a ) 4.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-[(2- hydroxybenzylidene)amino]ethyl}-3-methylimidazolium 71 hexafluorophosphate (2b ), and its metal complexes ( 3b , 4b and 5b ) from (2b ) 5.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy- 5-nitrobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate 89 (2c ), and its M(II) complexes ( 3c , 4c and 5c ) from ( 2c ) 6.1. Synthesis of the ionic liquid supported Schiff base, 1-{2-[(2- hydroxy-5-bromobenzylidene)amino]ethyl}-3-ethylimidazolium 109 tetrafluoroborate ( 2d ), and its metal complexes ( 3d , 4d and 5d ) from (2d ) 7.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy- 5-bromobenzylidene)amine]ethyl}-3-ethylimidazolium tetrafluoroborate 127 (2d ), and its M(III) complexes ( 6d and 7d ) from ( 2d ) 8.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy- 5-chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate 142 (2e ), and its metal complexes ( 3e , 4e and 5e ) from ( 2e ) 8.2. Synthesis of the M(III) complexes ( 6e , 7e and 8e ) from ( 2e ) 145

xix

LIST OF APPENDICES

Appendix Page No.

I: List of Publications 170-170

II. List of Communicated Articles 171-171

III. List of Other Publications 172-172

IV: Participation in Seminar, Symposium & Conferences 173-174

List of Abbreviations

ILs Ionic Liquids RTIL Room temperature ionic liquid FILs Functionalized ionic liquids M. p Melting point r. t Room temperature h hour g gram mL Millilitre. ᵒ C Degree in Celsius scale. MIC Minimum inhibition concentration. ppm parts per million AAS Atomic Absorption Spectroscopy MeOH Methanol EtOH Ethanol DMSO Dimethylsulfoxide DMF Dimethylformamide THF Tetrahydrofuran mmol milimol TLC Thin Layer Chromatography FTIR Fourier Transform Infrared MS Mass Spectroscopy 1H NMR Proton Nuclear Magnetic Resonance 13 C NMR Carbon-13 Nuclear Magnetic Resonance SEM Scanning Electron Microscopy s Singlet t Triplet d Doublet m multiplet Mol. Mt. Molecular weight KBr Potassium bromide Contd...

xxi

% Percentage K Unit of temperature in Kelvin scale.

[2-aemim]Br (1a) [1-(2-aminoethyl)-3-methylimidazolium bromide

[2aemim]PF 6 (1b) 1-(2-aminoethyl)-3-methylimidazolium hexafluorophosphate

[[2aeeim]BF 4 (1c) [1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate

[2aemim]BF 4 (1d) [1-(2-aminoethyl)-3-methylimidazolium tetrafluoroborate LH (2a) 1-{2-[(2- hydroxybenzylidene)amino]ethyl}-3- methylimidazolium bromide Mn(II) complex (3a) [Di(1-{2-(2- hydroxybenzylideneamino)ethyl}-3- methylimidazolium)Mn(II)]bromide CoII) complex (4a) [Di(1-{2-(2- hydroxybenzylideneamino)ethyl}-3- methyl imidazolium)Co(II)]bromide LH (2b) 1-{2-[(2- hydroxybenzylidene)amino]ethyl}-3- methylimidazolium hexafluorophosphate Mn(II) complex (3b) [Di(1-{2-(2- hydroxybenzylideneamino)ethyl}-3- methyl imidazolium)Mn(II)] hexafluorophosphate

Contd…

xxii

Co(II) complex (4b) [Di(1-{2-(2- hydroxybenzylideneamino)ethyl}-3- methylimidazolium)Co(II)] hexafluorophosphate

Cu(II) complex (5b) [Di(1-{2-(2- hydroxybenzylideneamino)ethyl}-3- methylimidazolium)Cu(II)] hexafluorophosphate LH (2c) 1-{2-[(2-hydroxy-5- nitrobenzylidene)amino]ethyl}-3- ethylimidazolium tetrafluoroborate Co(II) complex (3c) [Di(1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethyl imidazolium)Co(II)]tetrafluoroborate. Ni(II) complex (4c) Di(1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethyl imidazolium)Ni(II)]tetrafluoroborate. Cu (II) complex (5c) Di(1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethyl imidazolium)Cu(II)]tetrafluoroborate. LH (2d) 1-{2-[(2-hydroxy-5- bromobenzylidene)amino]ethyl}-3- ethylimidazolium tetrafluoroborate Co (II) complex (3d) [Di(1-{2-(2-hydroxy-5- bromobenzylideneamino)ethyl}-3-ethyl imidazolium)Co(II)]tetrafluoroborate. Ni (II) complex (4d) [Di(1-{2-(2-hydroxy-5- bromobenzylideneamino)ethyl}-3-ethyl imidazolium)Ni(II)]tetrafluoroborate. Cu (II) complex (5d) Di(1-{2-(2-hydroxy-5- bromobenzylideneamino)ethyl}-3-ethyl imidazolium)Cu(II)]tetrafluoroborate

Contd… xxiii

Fe(III) complex (6d) Di(1-{2-(2-hydroxy-5- bromobenzylideneamino)ethyl}-3-ethyl imidazolium) aqua chloro Fe(III)] tetrafluoroborate. Cr(III) complex (7d) Di(1-{2-(2-hydroxy-5- bromobenzylideneamino)ethyl}-3-ethyl imidazolium) aqua chloro Cr(III)] tetrafluoroborate LH (2e) 1-{2-[(2-hydroxy-5- chlorobenzylidene)amino]ethyl}-3- methylimidazolium tetrafluoroborate. Co(II) complex (3e) [Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium)Co(II)]tetrafluoroborate Ni(II) complex (4e) [Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium)Ni(II)]tetrafluoroborate Cu(II) complex (5e) [Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium)Cu(II)]tetrafluoroborate Mn(III) complex (6e) Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium) aqua chloro Mn(III)] tetrafluoroborate Fe (III) complex (7e) Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium) aqua chloro Fe(III)] tetrafluoroborate Cr (III) complex (8e) Di(1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methyl imidazolium) aqua chloro Cr(III)] tetrafluoroborate.

xxiv

CHAPTER I

Introduction Growing environmental consciousness has motivated the chemists around the world to search for environment benign solvents, non-polluting media for chemical synthesis as alternatives to the conventional volatile organic solvents. Chemical reactions generally depend on three conditions: solvent, reaction temperature and atmosphere. Among these conditions, a chemist can easily optimize the solvent system for a particular reaction keeping in view: i) solubility of the reactants, ii) reaction temperature and pressure, iii) product separation and purification, etc . The majority of solvents that used in academic and industrial laboratories are molecular liquids belong to the group of volatile organic compounds (VOC). These solvents are responsible for a large number of environmental problems and have a great impact on cost, safety and health. Furthermore, recovery and reuse of these chemicals are often associated with energy-intensive distillation and sometimes contamination. In the past few decades there have been numerous advances in synthetic organic methodologies that bypass the use of hazardous chemicals or VOC as solvents. Research in different chemical fields has led to search substitutes for toxic organic solvents and has proposed ionic liquids (ILs) as alternative solvents. Ionic liquids are almost identical with conventional molecular solvents, particularly in showing unique solubility against organic and inorganic materials. The interesting feature of ILs is that their formulations can be tailored at the molecular level by selection of desired constituent ions. ILs are now widely known solvents for different organic transformations and offer possibilities for improvement in the control of product distribution, enhanced reactivity, ease of product recovery, catalyst immobilization and recycling, etc . 1.1. Ionic Liquids (ILs) Ionic liquids are defined as organic salts that are typically composed of a large, asymmetric organic cation associated with an organic or inorganic counter anion and melt below 100 °C [1-3]. They are considered as nonaqueous green solvents or neoteric solvents and have drawn much attention worldwide. The interesting feature, i.e ., tenability of their physical and chemical properties by variation of ions makes these materials with almost unlimited possibilities, especially

General Introduction when considering an estimation of approximately 10 6 possible combinations of known cations and anions to form ionic liquids [4]. Typical IL cations are nitrogen containing such moieties such as alkylammonium, N,N/-dialkylimidazolium and N- alkylpyridinium or phosphorous containing moieties such as alkylphosphonium. The - - - - - common anions may include halides, BF 4 , PF 6 , CH 3CO 2 , CF 3CO 2 , NO 3 , - [(CF 3SO 2)2N] , etc . Some of the typical cations and anions used for the synthesis of ionic liquids are illustrated in Fig 1.1.

Fig 1.1. Some of the typical anions and cations used in ionic liquids preparation.

Ionic liquids have led to a new green chemical revolution owing to their unique physico-chemical properties [5, 6] such as: i) They have very low vapor pressure, low flammability and high ionic conductivity, ii) ILs possess an extensively wide temperature range of liquid state, so they are thermally stable and are applicable to reactions under high thermal conditions, iii) ILs can dissolve a large number of organic and inorganic materials and behave as highly polar aprotic solvent, iv) Most of the ILs exhibit limited or no toxicity. Due to these unique features, ILs are widely employed as solvents or reagents in a variety of applications like organic catalysis [7- 11], inorganic synthesis [12], biocatalysis [13-18], polymerization [19, 20] and engineering fluids [21-22] etc . Another important property of ILs is observed in the versatility of their design. Chemical modification of the structure of ILs can be

General Introduction tailored for a specific application. Due to this flexibility in structure modifications they have recently been investigated as solvents or materials for different pharmaceutical applications too [23-25]. Imidazolium-based ionic liquids are an important class of ILs among all the types of ionic liquids [26-28]. Their negligible vapor pressure allows their use to detect the size and shape of metal nanoparticles (NPs) through in situ X-ray photoelectron spectroscopy (XPS) or transmission electron microscopy (TEM) analyses [29, 30]. The supramolecular three-dimensional structural arrangement of imidazolium based ILs has a direct impact on their physicochemical properties and assists to illustrate their influence over several organic transformations [31]. Another remarkable property of these inidazolium- based ILs is their ability to dissolve large number of organic and inorganic compounds independently because of their polarities. This is due to their natural segregation in two main domains: polar and nonpolar [32]. As a result, polar substrates are preferentially dissolved in polar domains and vice versa [33-37]. The synthesis of ILs can generally be divided into two steps: first the formation of the desired cation and then anion exchange or metathesis. 1-methylimidazole is generally required for the preparation of imidazolium based ionic liquids. This is readily available at a reasonable cost from commercial sources and provides access to a large number of cations. Other N-substituted imidazoles are relatively expensive. 1- alkylimidazole can be synthesized easily in the laboratory [38] by refluxing imidazole with alkyl halide at 80 °C. A scheme is illustrated in Fig 1.2

. Fig 1.2 . Synthesis of imidazolium salt from alkyl halide

The anion exchange reaction is usually performed in suitable organic solvents [39]. This process was reported to give good yields and applied to synthesize various ILs - - - - - containing a wide variety of anions like PF 6 , BF 4 , SbF 6 , [CF 3SO 3] , [CF 3SO 2] and

General Introduction

Fig 1.3. Metathesis reaction of imidazolium moiety.

- (CF 3SO 2)2N , etc . The anion exchange reaction of the imidazolium moiety is illustrated in Fig 1.3.The lack of significant vapor pressure prevents the purification of ILs by distillation. Actually volatile impurities can be separated from ionic liquids by distillation. It is suggested to remove the impurities from the starting materials and to apply such synthetic process that generates few side products [39, 40]. Most of the ILs based on common cations and anions are colorless. But it is observed the products are often yellow colored, particularly during the quaternization step. The amount of impurity making this color is extremely small, often being undetectable in 1H-NMR or CHN microanalysis. 1.2. Functionalized ionic liquids [FILs] Functionalized ionic liquids (FILs) may be defined as ionic liquids in which a functional group such as hydroxyl, amino, sulfonic acid or carboxyl group and so on is introduced to the cation or anion (mostly cation) of the ILs [41]. The incorporation of this functionality makes the compound with a capacity to behave not only as a reaction medium but also as a reagent or catalyst for different chemical reactions [42, 43]. Conceptually, the functionalized ion is considered as possessing two elements. The first is a core that contains the ionic charge and acts as the locus for the second element, i.e. , the substituent group. In most of the cases, it is observed that the functional group of the FILs is cation-tethered. The FILs usually display similar physicochemical properties to those observed in case of pure ILs. 1.2.1. Functionalized Cations Although, the FILs are defined as ionic liquids in which functional group is incorporated to the cations or anions (or both) of the IL, subsequent research has focused on the introduction of functionality into the cations [44]. The most of the

General Introduction

Fig 1.4 . Synthesis of task specific ionic liquids

FILs have been prepared by quaternization of the imidazoles with a functionalized alkyl halide to afford the corresponding functionalized imidazolium halides in usually good yield [45]. General synthesis of FILs with functionalized cations from 1- alkylimidazoles is illustrated in Fig 1.4. FILs are designed to extract metal ions from an aqueous solution. While certain FILs have been developed to pull metals into the IL phase. The use of metal complexes dissolved in ionic liquids for catalytic reactions has been an interesting field of ionic liquid research to date. Still, this system has a tendency to leach dissolved catalyst into the co-solvents that are employed to extract the product of the reaction from the ionic liquid [46-48]. Some mono-functionalized cations and their field of applications [49, 50] are represented in Fig 1.5.

Fig 1.5 . Mono-functionalized imidazolium cations and their potential applications.

General Introduction

1.2.2. Functionalized Anions It is observed, compared to the FILs with functionalized cations, much less interest has been shown to the synthesis of ionic liquid systems with functionalized anions. Some examples with their potential applications [49] are shown in Fig 1.6.

Fig 1.6. Functionalized anions and their potential applications.

Although some of the important applications of FILs have been highlighted in Fig 1.5 and 1.6, they have potential catalytic applications which has attracted the researchers worldwide to continue work in this field. Furthermore, these ILs often play a decisive role in the synthesis of nanoparticles and nanostructures as particle stabilizing agents. Hence, ILs are usually considered as to be highly polar, yet, often weakly coordinating solvents. Solvatochromatic investigation reveals that ionic liquids have properties similar to those of small-chain alcohols and other polar, aprotic solvents (DMSO, DMF, etc. ) [51-53]. So, their polarity is intermediate between water and chlorinated organic solvents and varies within the region depending on the nature of the IL components. By changing the nature of the ions present in ionic liquids, the properties of the ionic liquids can be altered. For example, the solubility of water in ILs can be changed from complete miscibility to almost total immiscibility, tailoring - - the anions from Cl and PF 6 . ILs are found to be immiscible with alkanes and other non-polar organic solvents and hence can be used in two-phase systems. Similarly,

General Introduction hydrophobic ILs can be designed and used in aquous/IL biphasic systems. They are alternatives to the conventional organic solvents in liquid/liquid separation [54-56]. From the synthetic perspective the important features of an ionic liquid are: і) catalyst solubility, catalyst activity, immobilization to extraction processes; іі ) reagent solubility and ііі ) product extractability. Solubility of metal ions in ILs can be divided into processes involving the dissolution of sample metal salts, often through coordination with anions from the ionic liquid and the dissolution of metal coordination complexes in which the metal coordination remains unaffected. Simple metal compounds are poorly soluble in non- coordinating ILs. Addition of lipophilic ligands enhances the solubility of metal ions in ionic liquids. Ionic complexes are observed to be more soluble in ILs than the neutral complexes. Transition metal salts and complexes are used as homogeneous catalyst in ionic liquid systems [57-60]. ILs have also been used as inert additives to stabilize transition metal catalyst in an organic solvent systems [61, 62]. The extremely low solubility of ionic liquid component solubilizes the catalyst upon concentration and removal of organic solvent and product. By this way, ILs preventing catalyst decomposition and enabling recycling and reuse of catalyst in batch processes [63, 64]. On the contrary, the biological properties of ILs are dependent on both their cations and anions. Usually ILs, with long alkyl substituents, exhibit anti-microbial activity and weak mutagenic properties towards plants. It is seen that large numbers of ionic liquids exhibited no significant toxicity for animals [65]. In addition, ILs have many favorable features to replace organic solvents for the formation of pharmaceutical compounds. They often led to higher yields, better selectivity and simple product isolation. The reaction process involving ionic liquids may be homogeneous or heterogeneous phases, providing a higher flexibility in manipulating the reactions. ILs are preferable for both chemical and enzymatic synthesis of drug molecules [66-75]. 1.3. Schiff Bases Schiff bases are termed as “privileged” ligand due to their simple synthesis procedures and vast range of applications in different field [76]. These organic compounds are very much available, versatile and based on the characteristics of

General Introduction precursors they show different denticities and functionalities. The nature, number and relative position of the donor sites of a Schiff base permit a good control over the geometry of the metallic centers. Owing to the structural diversity and preparative accessibility they play essential roles both in the synthetic and structural research [77]. Most of the Schiff bases and their corresponding metal complexes have been investigated owing to their important and attracting properties, such as, their ability to bind oxygen, photo chromatic properties, catalytic activity in hydrogenation of olefins and complexing capability towards toxic metals [78-82]. Schiff bases play a vital role in the enzymatic or unenzymatic transminating reactions of the carbonyl compounds with amino acid [83]. They also provide options for generating substrate chirality and increasing the solubility and stability of homogeneous and heterogeneous catalyst [84]. Furthermore, Schiff bases are considerably used in medicinal and pharmaceutical field. The presence of toxophoric linkage ( i.e. , -HC=N- linkage) in the structure allows them to show biological applications including antibacterial [85, 86], antifungal [87] and antitumor activity [88]. Schiff bases are organic materials containing azomethine linkage (-HC=N-) generally formed by condensation of the primary amines with a carbonyl compound [89, 90]. Hugo Schiff in 1864 first reported this organic compound [91]. The common structural property of Schiff bases is presence of the azomethine group in their structure, with the general formula RHC=N-R/ (where R and R / are alkyl, aryl, cycloalkyl or heterocyclic groups). The common synthetic path of synthesis of Schiff bases is mentioned in Fig 1.7.

Fig 1.7. Synthesis of Schiff base from amine and carbonyl precursor.

Like aldehydes, ketones may be used in the synthesis of Schiff bases although ketones produce these compounds less readily than aldehydes. Furthermore, Schiff bases derived from the aliphatic aldehydes are less stable and easily polymerize [92]. The

General Introduction aromatic aldehydes having potent conjugated systems are more stable. The lone pair of electrons on the sp 2 hybrid orbital of nitrogen atom of azomethine linkage has substantial chemical and biological significance [93] and exhibit excellent chelating capability, when applied incorporation with one or more donor atoms adjoining to the azomethine linkage. The coordination nature of the Schiff bases depends on the carbonyl and amine molecules employed in condensation reaction. They may behave as bi-, tri-, tetra-, penta- or polydentate ligand based on the number of donor atoms present in the particular structure. Examples are given in Fig 1.8.

Fig 1.8. Schiff bases with mono-, bi-, tri- and tetra donor atoms.

Salicylaldehyde and its derivatives are most applicable carbonyl precursors for the preparation of a wide variety of Schiff bases [94, 95]. Now a days extensive research is going on the modification of Schiff base ligand to extend their applications in the area of synthesis and catalysis. Ionic liquid-supported Schiff base ligand is the results of such modification, where amine functionalized ionic liquids are condensed with aromatic aldehydes [96]. Formation of Ionic liquid-supported Schiff bases is represented in Fig 1.9.

General Introduction

Fig 1.9. Synthesis of Ionic liquid-supported Schiff bases.

Ionic liquid-supported Schiff bases are found to be most convenient and attractive ligand for the forming of complexes with different metal ions owing to some important reasons. Mainly, steric and electronic consequences around the metal centre can be finely altered by a suitable selection of bulky or electron donating or withdrawing substituent included into the Schiff bases [97]. Again, the donor sites (N and O) of the coordinated Schiff bases show two opposite electronic effects: the phenolate oxygen atom is hard donor and stabilizes the higher oxidation states of the metal atom; whereas the imine nitrogen atom is borderline donor and stabilizes the lower oxidation state of the corresponding metal ion [98]. Their basicity also exhibits a vital role in the synthesis and stabilization of the complexes. The functional groups such as –OH and –SH, available in the Schiff bases can generate tautomerism in them leading to complexes with various geometries. The keto-enol tautomerism of Ionic liquid-supported Schiff base is shown in Fig 1.10.

Fig 1.10. Keto-enol tautomerism of IL-supported Schiff base.

Ionic liquid-supported Schiff bases have vast range of applications in synthetic, catalytic and biological field. They are used to make suitable air stable and water

General Introduction soluble catalyst for various types of organic transformations to establish methodology for C-C coupling reactions [99]. These novel Schiff base ligands are also applied in the metal catalyzed coupling reactions to get excellent yields [100, 101]. Furthermore, they are designed for the binding of metal ions from aqueous solutions. Example of such kind of Schiff base [5] applied in the extraction of Ni 2+ ion from aqueous solution is shown in Fig 1.11.

Fig 1.11 . Extraction of Ni 2+ ion from aqueous solution.

The Schiff base quickly decolorizes green aqueous solutions containing Ni 2+ with which it is placed into contact, the color moving completely into the ionic liquid phase. In Schiff bases azomethine (-HC=N-) linkage is essential for biological activity, ionic liquid-supported Schiff base ligands were also reported to possess remarkable antibacterial and microbiocidal activities [102]. 1.4. Transition Metal Complexes of Schiff Bases Transition metal complexes of Schiff base are well known to chemist since 1840, when bis(salicyldimino)Cu(II) was isolated as dark green crystalline solid, by the reaction of cupric acetate with salicylaldehyde and aqueous ammonia [103]. They are one of the most adaptable and thoroughly studied systems in coordination chemistry due to easy synthesis techniques and the synthetic flexibility, enable designs of compounds with different structural properties [104, 105]. The Schiff bases and its transition metal complexes are being studied extremely by researchers owing to their interesting chemical and physical properties and huge applications in different scientific areas [106-108]. These complexes have also important applications in clinical [109] and analytical [110] fields. Again, some of the complexes are applied as model molecules for biological oxygen transporter system [111]. The transition metals are involved in many biological reactions that are very essential to life process

General Introduction

[112, 113]. The Schiff base metal complexes have useful applications in different field of human interest [114-119]. A large number of paper have been published on relationship between metal ions and their corresponding metal complexes as antitumor and antibacterial agents which is a subject of great interest [120-122]. Schiff base their metal complexes were well established since the mid nineteenth century. The work of two famous scientists Jorgensen and Werner on these metal complexes was gained interest of chemists in the area of coordination chemistry [123]. Pfeiffer and his group [124] mentioned a series of complexes synthesized from Schiff bases of salicylaldehyde and its derivatives. The main privilege of the salicyladiimines ligand is the considerable flexibility of the synthetic procedures facilitating in the synthesis of a wide variety of complexes with a given metal ion whose properties often depend on the ligand structure. Transition metal complexes of Schiff bases are usually formed by adding a metal salts with the Schiff base ligands under suitable experimental conditions. Detailed discussion on synthesis and structural characterization of Schiff base and its metal complexes are available in numerous literatures [125, 126]. In recent years, more attention has been grown on the Schiff base ligands carrying both amino (-NH 2) and hydroxyl (-OH) groups for coordination with suitable metals ions [127]. This is due to the facts that they can be employed for generating substrate chirality, altering the metal centered electronic factor and increasing the solubility and stability of either homogenous or heterogeneous catalysts [128]. Many research articles [129-134] covering the area of synthesis to physico-chemical and biochemically relevant studies on Schiff bases metal complexes revealed that such complexes are very much relevant with the development of modern coordination chemistry. Furthermore, Schiff bases are capable to stabilize various metal ions in different oxidation states and thus control the activity of metals ions in wide variety of effective catalytic transformations [135]. In this regard, the transition metal complexes of Ionic liquid-supported Schiff bases, obtained from different aromatic aldehydes and amine functionalized ionic liquids have become a subject of major interest [100, 101]. The complexes are extensively used as catalyst in numerous numbers of organic transformations as this type of catalyst can easily be reused for five or six steps

General Introduction

Fig 1.12. Synthesis of Ionic liquid-supported Pd(II) complex. without much loss of activity and showing an example of sustainable and green methodology. Most of the catalysts are hydrophilic in nature, results in easy separation and recycling of the catalyst from the product. An example is given in Fig 1.12.Thus the ionic liquid-supported Schiff base complexes of transition metal ions have played a key role in many organic transformations to enhance the yield and product selectivity. The suitable path of synthesis and thermal stability of the metal complexes have contributed notably for their possible application in catalysis [99]. The transition metal ions combined such Schiff base ligands show high catalytic activities in reactions of industrial importance and academic interests. It is known that almost all the transition metal complexes of Schiff base ligand exhibits excellent antiviral, anticancer, antibacterial and antimicrobial activity [136, 137]. The potential biological activity can related to the presence of nitrogen atom with a lone pair of electron in it and that the nitrogen can participate in hydrogen bonding with OH or NH groups present in bio-molecules. 1.5 Literature review Ionic liquids may be considered as a new and remarkable class of solvents that has a long and interesting history. The first ionic liquids ethyl ammonium nitrate was reported in 1914 by the famous scientist Walden and his coworkers [138] and this IL is a liquid at room temperature. Osteryoung and his group prepared ethylpyridinium bromotrichloroaluminate(III) ([EtPy][AlBrCl 3]) and characterized its chemical and electrochemical properties [139]. In 1983, Hussey first mentioned the term “ionic liquid” to these special molten salts [140]. Wilkes et al. , in 1992, reported the

General Introduction

synthesis of 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF 4]) and1- ethyl-3-methylimidazolium acetate ([emim[OAc]), and introduced the field of modern research on ionic liquids [141]. Dupont and his coworkers in 1996, developed an important ionic liquid, 1-butyl-3-methyl imidazolium hexafluorophosphate

([bmim][PF 6]), that exhibits hydrophobic nature [142] and strongly simulated chemists to apply them as solvents for different types of chemical reactions especially in organic reactions. In 1998 the formation of ILs by large, assymetric ions derived from the antifungal drug miconazole was reported by Davis et al ,. [143]. The report explianed the possibilities for formulating salts that remain in the liquid state at low temperature, even while introducing functional groups in the ion structure and promoted the introduction of the concept of task-specfic ionic liquid [144]. The same group reported the synthesis of functionalized cations for task-specfic ionic liquids, starting from 1-(3 aminopropyl)imidazole and uses of ILs containing functionalized ions [145, 146]. A schematic route for the synthesis of TSILs was given in Fig 1.13.

Fig 1.13. Synthesis of TSIL.

Wasserscheid et al. [147] introduced a complimentary method for TSIL synthesis using the Michael reaction which is shown in Fig 1.14. Song and his co-worker mentioned the synthesis of amine-functionalized ionic liquid and used it as an efficient nucleophilic scavenger in solution phase combinatorial synthesis [148]. The synthesis of amine-functionalized IL is depicted in Fig 1.15.

General Introduction

Fig 1.14. Synthesis of TSIL using Michael reaction.

Fig 1.15. Synthesis of amine functionalized ionic liquid.

Gu et al., [149] reported the synthesis of SO 3H-functionalized ILs, which showed a dual role as both a reusable catalyst and a solvent for oligomerization of various olefins. Song et al ., [150] investigated on the synthesis of functionalised ionic liquids and their applications as recoverable catalysts for organic reactions and metal scavenger. The same group [151] also reported the synthesis and use of IL grafted Mn(III) Schiff base complex as a highly efficient and recyclable catalyst for the epoxidation of chalcones. Singer et al , [152] reported the synthesis and X-ray crystal structure of a metal chelate prepared from an imidazolium based TSIL with an

General Introduction

Fig 1.16. Synthesis of Cu[EDA-mim] 2 (Adapted from Ref. No. 152). ethylaminediacetic acid as the chelating moiety. The ligand reported by them formed 1:2 (M:L) complex with Cu 2+ ion and the reaction is illustrated in Fig 1.16. Ranu et al [153] published several research papers related to the use of ionic liquids as catalyst as well as a reaction medium for useful transformations. Nicasio and Perez group [154] showed the synthesis of IL based Cu + complex and its use as catalyst for the transfer of :CHCO 2Et unit from ethyldiazo acetate to several saturated and unsaturated substrates with high yields under the biphasic condition with [bmim]PF 6 and hexane as the reaction medium. D.C. Forbes et al [155] reported the formation and application of an imidazolium dirhodium(II) carboxylate metal complex as an active catalyst in the intermolecular cyclopropanation reaction of styrene using ethyl diazoacetate. The pictorial representation is given in Fig 1.17.

General Introduction

Fig 1.17. Synthesis of imidazolium dirhodium(II) carboxylate. Adapted from Ref. No. 155.

The synthesis of some IL-supported Schiff bases by condensation of some aromatic aldehydes with the amine functionalized ionic liquids without solvent was reported by Li et al [156]. The recovery often posess great difficulties and immobilization seems to be a good strategy but the nature of the insoluble supports may suffer from limited activity and accessibility to substrates. Zhao and Peng et al ., [157, 158] revealed that IL bonded to chiral salen Mn(II) complex can enhance catalytic efficiency and recovery of the in situ formed complex which often showed great difficulties. Yin and his co-workers [159] synthesized chiral oxovanadium(IV) Schiff base complex functionalized by ionic liquid for enantioselective oxidation of methyl aryl sulphides. The synthesized complex was detected as an efficient catalyst and could be isolated conveniently by simple precipitation with addition of hexane and was recycled several times without loss of activity and enantioselectivity. The synthesis of the complex was shown in Fig 1.18.

General Introduction

Fig 1.19 Synthesis of the chiral oxovanadium(IV) complex. Adapted from Ref. No. 159.

Shi et al [160] synthesized the hydrophobic amino-functionalized ionic liquid and reported its extraction behavior for Cu 2+ ion as a model cation. The IL, owing to the presence of an amino group, is capable of chelating Cu 2+ ion and was successfully applied as standard reference material to the analysis of Cu 2+ ion in environmental water. Kumar and his group [161, 162] reported the synthesis, structural, characterization and microbiocidal activities of ionic liquid tagged Schiff bases. They also used ionic liquid-supported aldehydes as a scavenger to remove primary amines in the synthesis of secondary amines in the solution phase. The synthesis of novel imidazolium ionic liquid-supported Schiff is shown in Fig 1.19.

Fig 1.19. Synthesis of IL-supported Schiff base. Adapted from Ref. No. 161.

The same group recently synthesized air stable, water soluble Pd(II) complex of an ionic liquid tagged Schiff base. The complex was used as an efficient catalyst for Suzuki-Heck cross coupling reaction in water medium [163].

General Introduction

1.6. Object and Application of the Research work Chemistry of functionalized ionic liquids can be regarded as young chemistry, which has drawn chemist’s attention not only in organic transformations but also in catalysis especially immobilizing phase for biphasic catalysis, biocatalysis, biotransformation [164-165], pharmaceuticals and extending its wave to every laboratory including academia and industry. Recently, metal-containing functionalized ionic liquids have been found to be more promising salts as they can merge the features of ionic liquids with the catalytic properties of the incorporated transition metal ions [166-167]. In the field of catalysis, there is always a requirement for the invention of an efficient, vigorous and cost effective catalyst that can overcome the drawbacks of the existing catalysts [168-169]. Moreover, environmental awareness and economic consideration compel chemists to develop such a catalytic system that can be revived and reused, especially when harmful metal ions are involved [170-171]. The biological properties of the ionic liquids depend on both their cations and anions [172]. Generally, ILs with long alkyl substituent display significant antibacterial, antimicrobial activity and weak mutagenic properties towards plants although they show less toxicity against animals [172]. In recent years considerable attention has been focused on the modification of Schiff base ligands as their transition metal complexes have wide application in the area of synthesis, catalysis, pharmaceutical and biological activities [173, 136]. However, the synthesis of transition metal complexes from ionic liquid-supported Schiff base ligands and their biological applications in broad range remain unexplored. This research work focuses on: i) the synthesis and physico-chemical characterization of ionic liquid-supported Schiff bases and their transition metal complexes and ii) Exploration of the antibacterial activities of the synthesized compounds against some naturally available gram positive and gram negative bacteria.

General Introduction

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27 CHAPTER II

Experimental Section 2.1. Materials All the chemicals were of analytical grade and were used without further purification. The most of the solvents were of spectroscopic grade and used as received from the commercial sources. The list of reagents and solvents used is given in Table 2.1.

Table 2.1. List of reagents and solvents. Chemicals M.W (g/mol) Source CAS No.

1-methyl 82.1 Hi-Media. Lab. Pvt. Ltd. 616-47-7 imidazole 1-ethyl imidazole 96.13 Sigma-Aldrich, 7098-07-9 Germany 2- 204.89 Sigma-Aldrich, 2576-47-8 bromoethylamine Germany hydrobromide Sodium 109.79 Sigma-Aldrich, 4316-42-1 tetrafluoroborate Germany Potassium hexa 184.06 Sigma-Aldrich, 17084-13-8 fluorophosphates Germany Salicyldehyde 122.12 S. D. Fine Chemicals, 90-02-08 India 5-bromo 201.019 Sigma-Aldrich, 1761-61-5 salicyldehyde Germany 5-chloro 156.57 Sigma-Aldrich, 635-93-8 salicyldehyde Germany 2-hydroxy-5-nitro 167.12 Sigma-Aldrich, 97-51-8 benzaldehyde Germany Cupric acetate 181.63 S.D.Fine Chemicals, 37829K02 India Cobalt acetate 177.021 Merck, India 6147-53-1 Nickel acetate 176.78 Thomas Baker 6018-89-9 Manganese 173.03 Sigma-Aldrich, 638-38-0 acetate Germany Ferric chloride 162.195 Thomas Baker 7705-08-0

Experimental Section

Chromium 266.44 Thomas Baker 10060-12-5 chloride Methanol 32.04 S. D. Fine Chemicals, 67-56-1 India Dimethylsulfoxid 78.13 S. D. Fine Chemicals, 67-68-5 e India Acetonitrile 41.05 S. D. Fine Chemicals, 75-05-8 India Water 18.015 Merck, India 7732-18-5 Sodium 39.99 Merck, India 1310-73-2 hydroxide Ethanol 46.07 S. D. Fine Chemicals, 64-17-5 India Chloroform 119.38 S. D. Fine Chemicals, 67-66-3 India Diethyl ether 74.12 S. D. Fine Chemicals, 60-29-7 India

2.2. Experimental Methods 2.2.1. Physico-chemical methods used to characterize synthesized compounds Different physico-chemical techniques have been used to characterize the structure of Schiff base ligands and their metal complexes. A brief account of these methods is given below. a) Elemental analysis: Elemental micro-analyses (C, H and N) of all the synthesized compounds were performed by using Perkin–Elmer (Model 240C) analyzer. The metal contents in the complexes were determined with the help of Atomic Absorption Spectrophotometer (Varian SpectrAA 50B) by using standard metal solutions procured from Sigma-Aldrich, Germany.

Experimental Section

Fig 2.1. Atomic Absorption Spectrophotometer (Varian SpectrAA 50B)

b) Magnetic susceptibility measurement: Magnetic susceptibilities were measured at room temperature with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1). The MSB works on the basis of a stationary sample and moving magnets. The pairs of magnets are placed at opposite ends of a beam so placing the system in balance. Introduction of the sample between the poles of one pair of magnets produces a deflection of the beam that is registered by means of phototransistors. A current is made to pass through a coil mounted between the poles of the other pair of magnets, producing a force restoring the system to balance. At the position of equilibrium, the current through the coil is proportional to the force exerted by the sample and can be measured as a voltage drop. The solid sample is tightly packed into weighed sample tube with a suitable length ( l) and noted the sample weight ( m). Then the packed sample tube was placed into tube guide of the balance and the reading ( R) was noted. The gram susceptibility,

χ g , is calculated using: ( R − R ) χ = C × l × 0 )1( g Bal m × 10 9 where l = the sample length (in cm), m = the sample mass (in g), R = the reading for the tube plus sample, R0 = the empty tube reading and CBal = the balance calibration constant. Thus molar susceptibility is χ M = χ g × M. Wt of the sample .

Experimental Section

The molar susceptibility is the corrected with diamagnetic contribution. The effective magnetic moment, µeff , is then calculated by using the following expression:

µ eff = 83.2 T × χ A B.M )2( where χ A is the corrected molar susceptibility.

Fig 2.2. (Magway MSB Mk1).

c) Melting point: The melting point of the ligand and complexes were determined by open capillary method with the aid of melting point apparatus.

Fig 2.3. Melting point apparatus

Experimental Section

d) Thin layer chromatography: The purity of the prepared compounds was confirmed by thin layer chromatography (TLC) on silica gel plates and the plates were visualized with UV-light and iodine as and when required. e) Powder X-ray diffraction (PXRD): Powder X-ray diffraction (XRD) data were obtained on a D8 Advanced Bruker using Cu K α radiation (2 θ= 0-90˚).

Fig 2.4. D8 Advanced Bruker.

f) Infrared spectra: Infrared spectra (KBr pellets) were recorded on a Perkin- Elmer Spectrum FT-IR spectrometer (RX-1) operating in the region 4000 to 400 cm -1. KBr for IR spectroscopy from Sigma-Aldrich, Germany was used for preparing the pellets after drying the salt in a drying pistol over anhydrous CaCl 2 for 24 hours and then kept in vacuum desiccators over anhydrous CaCl2 before use.

Experimental Section

Fig 2.5. Perkin-Elmer Spectrum FT-IR spectrometer (RX-1)

g) Electronic spectra: Electronic spectra of the ligands and its complexes in methanol were recorded on a Jasco V-530 double beam UV-VIS spectrophotometer at 298.15 K. It was coupled with a thermostatic arrangement and maintained at 298.15 K. A quartz cell of 1 cm path length was used for the spectral measurements.

Fig 2.6. Jasco V-530 double beam UV-VIS spectrophotometer

Experimental Section

h) 1H-NMR and 13 C-NMR: 1H-NMR and 13 C-NMR was recorded on a FT- NMR (Bruker Avance-II 400 MHz) spectrometer at room temperature by using

DMSO-d6 and D 2O as solvents.

Fig 2.7. FT-NMR (Bruker Avance-II 400 MHz).

i) Conductivity: Specific conductance was measured at (298.15 ± 0.01) K with a Systronic conductivity TDS-308 meter. The conductance measurements were carried out by using a dip-type immersion conductivity cell, CD-10 with a cell constant of 1.0 ± 10% cm -1. The instrument was standardized by using 0.1 (M) KCl solution. Measurements were made in a thermostatic water bath maintained at the experimental temperature with an accuracy of ± 0.01 K.

Fig 2.8. Systronic conductivity TDS-308 meter.

Experimental Section

j) Mass Spectra: Mass spectra were recorded on a JMS-T100LC spectrometer.

Fig 2.9. JMS-T100LC spectrometer.

k) Thermal Analysis (TGA): Thermal analysis (TGA) was performed in a temperature range of 25-800 oC (heating rate 10 oC/min) with 4000 Perkin–Elmer thermal analyzer in Al 2O3 crucible under nitrogen atmosphere.

Fig 2.10. 4000 Perkin–Elmer thermal analyzer.

2.2.2. Mass measurements Mass measurements were carried out on digital electronic analytical balance (Mettler Toledo, AG 285, Switzerland) as shown in figure 3.23.

Experimental Section

Fig 2.11. Digital electronic analytical balance (Mettler Toledo, AG 285).

This Digital balance can measure mass to a very high precision and accuracy. The mass measurements were accurate to ± 0.01 mg. 2.2.3. Antibacterial assay Antibacterial activity of the synthesized compounds were studied in vitro against gram positive and gram negative bacterial strains by agar disc diffusion method and paper disc method [1-4]. All the bacterial strains were procured from MTCC, Chandigarh; India. The nutrient agar (Hi-Media Laboratories Limited, Mumbai, India) was autoclaved at 12l °C and 1 atm for 15-20 minutes. The sterile nutrient media was kept at 45-50 °C, after that 100 µL of bacterial suspension containing 10 8 colony-forming units (CFU)/mL were mixed with sterile liquid nutrient agar and poured into the petri plates. Upon solidification of the media, filter disc (5mm diameter) was individually soaked with different concentration (suitable for the sample) of each extract and placed on the solidified nutrient agar media plates. The different concentrations were made by diluting with DMSO. The plates were incubated for 24 h at 37 °C. The diameter of the zone of inhibition (including disc diameter of 5 mm) was measured with a scale. The lowest concentration of sample extract that inhibited bacterial growth was considered as minimum inhibitory concentration (MIC). MIC was measured by Broth Micro dilution susceptibility method. In this work, the synthesized compounds were tested against some gram

Experimental Section positive and gram negative bacteria. The details regarding these bacteria were given below: 2.2.3.1. Gram negative bacteria 2.2.3.1a. Escherichia coli Escherichia coli (E. coli ) is a gram-negative, anaerobic, rod- shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination [5].

Fig 2.12. E. coli bacteria.

2.2.3.1b. Pseudomonas aeruginosa P. aeruginosa is a common gram-negative, rod-shaped bacterium that causes disease in plants and animals, including humans. P. aeruginosa is a multidrug resistant pathogen, recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – especially hospital- acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. Treatment of P. aeruginosa infections can be difficult due to its natural resistance to antibiotics. When more advanced antibiotic drug regimens are needed adverse effects may result [5].

Experimental Section

Fig 2.13. Pseudomonas aeruginosa bacteria.

2.2.3.1c. Proteus vulgaris P. vulgaris is a rod-shaped, nitrate-reducing, and catalase-positive, hydrogen sulfide-producing, gram-negative bacterium that inhabits the intestinal tracts of humans and animals. It can be found in soil, water, and fecal matter. It is an opportunistic pathogen of humans. It is known to cause wound infections and other species of its genera are known to cause urinary tract infections [5].

Fig 2.14. P. vulgaris bacteria.

2.2.3.1d. Enterobacter aerogenes It is a gram negative, catalyse positive, indole negative, rod-shaped bacterium. E. aerogenes is nosocomial and pathogenic bacterium that causes opportunistic infections including most types of infections. The majority is sensitive to most antibiotics designed for this bacteria class, but this is complicated by their inducible resistance mechanism which means that they quickly become resistant to standard antibiotics during treatment, requiring a change in antibiotic to avoid

Experimental Section worsening of the sepsis. Some of the infections caused by E. aerogenes result from specific antibiotic treatments, venous catheter insertions and surgical procedures. E. aerogenes is generally found in the human gastrointestinal tract and does not generally cause disease in healthy individuals. It has been found to live in various wastes and soil [5].

Fig 2.15. Enterobacter aerogenes bacteria.

2.2.3.1e. Klebsiella pneumoniae K. pneumoniae is a gram-negative, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. Although found in the normal flora of the mouth, skin, and intestines, it can cause destructive changes to human and animal lungs if aspirated (inhaled), specifically to the alveoli (in the lungs) resulting in bloody sputum. In recent years, Klebsiella species have become important pathogens in nosocomial infections. It naturally occurs in the soil, and about 30% of strains can fix nitrogen in anaerobic conditions. Its nitrogen-fixation system has been much-studied due to agricultural interest as K. pneumoniae has been demonstrated to increase crop yields in agricultural conditions [5].

Fig 2.16. K. pneumoniae bacteria

Experimental Section

2.2.3.2. Gram positive bacteria 2.2.3.2a. Bacillus subtilis B. subtilis is a gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants and humans. B. subtilis is rod-shaped, and can form a tough, protective endospore, allowing it to tolerate extreme environmental conditions [5].

Fig 2.17. B. subtilis bacteria. 2.2.3.2b. Bacillus cereus B. cereus is a gram-positive, rod-shaped, aerobic, beta hemolytic bacterium commonly found in soil and food. Some strains are harmful to humans and cause food borne illness, while other strains can be beneficial as probiotics for animals [5].

Fig 2.18. B. cereus bacteria.

Experimental Section

2.2.3.2c. Staphylococcus aureus S. aureus is a gram-positive, round-shaped bacterium that is frequently found in the nose, respiratory tract, and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus is not always pathogenic, it is a common cause of skin infections such as a skin abscess, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of cell- surface proteins that bind and inactivate antibodies [5].

Fig 2.19. S. aureus bacteria.

2.2.4. Synthesis of functionalized ionic liquids (FILs) 2.2.4.1. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium bromide, [2- aemim][Br (1a) The functionalized ionic liquid was synthesized with slight modification of a literature procedure [6]. A mixture of 1-methylimidazole (4.10 g, 0.05 mol) and 2- bromoethylamine hydrobromide (10.25 g, 0.05 mol) was taken in a round bottomed flask equipped with air condenser and added ethanol (50 mL) as solvent. The reaction mixture was refluxed under nitrogen atmosphere at 80 °C for 24 h. On completion of the reaction, the solvent was distilled off and the residue was recrystallized from ethanol and ethyl acetate. The resultant white powder was dissolved in methanol and then NaOH (2.00 g, 0.05mol) was added to react for 8 h at room temperature. The excess NaOH were filtered off and the solvents were evaporated under vacuum. The

Experimental Section obtained product was washed successively with diethyl ether. After drying for 6 h under vacuum at 80 °C, the expected ionic liquid was obtained as dark brown oil (Fig 2.20).

Fig 2.20. 1-(2-aminoethyl)-3-methyllimidazolium bromide, [2-aemim]Br.

[2-aemim]Br ( 1a ): Dark brown oil; 7.11 g (yield, 67 %). Anal. Calcd. for C 6H12 N3Br (213): C, 34.97; H, 5.87; N, 20.39 %. Found: C, 34.71; H, 5.77; N, 20.11 %. FT-IR (KBr, cm -1): 3429 (N-H), 2994, 1624 (C=N), 1172, 756, 621. 1H NMR (400 MHz,

D2O) δ: 3.83 (t, 2H, NH 2-CH2); 4.49 (s, 3H, C H3), 4.55 (t, 1H, N-CH2), 7.40 (s, 1H, 13 NC H), 7.49 (s, 1H, NC H), 8.54 (s, 2H, N H2), 8.81 (s, 1H, N( H)CN); C-NMR (400

MHz, D2O) δ: 124.58, 123.12, 122.44, 53.46, 50.12, 39.08.. ESI-MS (CH 3OH, m/z ): 126.20 [(M-Br)+]. The 1H NMR, 13 C NMR, FT-IR and ESI-MS spectra are given below.

Fig 2.21. FT-IR spectrum of [2-aemim]Br

Experimental Section

Fig 2.22 . 1H NMR spectrum of [2-aemim]Br.

Fig 2.23. 13 C NMR spectrum of [2-aemim]Br.

Experimental Section

Fig 2.24. ESI-MS spectrum of [2-aemim]Br.

Scheme 2.1. Synthesis of [2-aemim]Br (1a ).

2.2.4.2. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium hexafluorophosphate, [2-aemim]PF 6 (1b) Following literature procedure [7] a mixture of 1-methylimidazole (4.10 g, 0.05 mol) and 2-bromoethylamine hydrobromide (10.25 g, 0.05 mol) in 25 mL of acetonitrile was heated with constant stirring at 80 °C for 4 h. On completion, the solvent was removed by distillation, and the residue was recrystallized from ethanol

Experimental Section

to afford the hydrobromide of [2-aemim][Br] as a white solid. Then KPF 6 (9.20 g,

0.05 mol) was added to hydrobromide of [2-aemim][Br] in 20 mL of CH 3CN/H 2O (1:1, v/v). The solution was left for 24 h at room temperature and then NaOH (2.00 g, 0.05 mol) was added for neutralization. Solvents were evaporated under vacuum. This was followed by the addition of CH 3OH (2 mL) and CHCl 3 (10 mL). The precipitated KBr were filtered off and the solvents were evaporated. The obtained yellow oil was washed successively with chloroform (10 mL × 3) and ether (10 mL × 3). After drying for 6 h under vacuum at 80 °C, the expected ionic liquid was obtained (Fig 2.25).

Fig 2.25. 1-(2-aminoethyl)-3-methyllimidazolium hexafluorophosphate, [2-aemim]PF 6

[2-aemim]PF 6 (1b ): Yellow oil; 9.35 g (yield, 69 %). Anal. Calcd. for

C6H12 F6N3P (271): C, 26.58; H, 4.46; N, 15.50. Found: C, 26.32; H, 4.42; N, 15.36 %. FT-IR (KBr, cm -1): 3429 (N-H), 3106, 2365, 1617 (C=N), 1175, 846 (P-F). 1H NMR

(400 MHz, D2O) δ: 3.26 (t, 2H, NH 2-CH2); 3.83 (s, 3H, C H3), 4.44 (t, 1H, N-CH2), 13 7.39 (s, 1H, NC H), 7.48 (s, 1H, NC H), 8.52 (s, 2H, N H2), 8.79 (s, 1H, N( H)CN); C-

NMR (400 MHz, D2O) δ: 136.87, 124.53, 122.97, 53.35, 36.01, 27.88. ESI-MS + 1 13 (CH 3OH, m/z ): 126.20 [(M-PF 6) ]. The H NMR, C NMR, FT-IR and ESI-MS spectra are given below.

Experimental Section

Fig 2.26. FT-IR spectrum of [2-aemim]PF 6.

Fig 2.27 . ESI-MS spectrum of [2-aemim]PF 6.

3.2.4.3. Synthesis of 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2- aeeim]BF 4 (1c )

The amino functionalized ionic liquid [2-aeeim]BF 4 was synthesized by following a literature procedure [7]. 1-ethylimidazole (4.80 g, 0.05 mol) and 2- bromoethylamine hydrobromide (10.25 g, 0.05 mol) were taken in acetonitrile (25 mL), the mixture was heated with constant stirring at 80 °C for 4 h. The solvent was

Experimental Section removed by distillation and the resulting residue was washed with ethanol and then 20 ml of CH 3CN/H 2O (1:1, v/v) and NaBF 4 (5.5 g, 0.05 mol) were added. The mixture was left for 24 h at room temperature with constant stirring and then neutralized by NaOH (2.00 g, 0.05 mol). Solvents were evaporated in vacuo followed by adding methanol (20 mL) and chloroform (2 mL), the precipitated NaBr was filtered off and the solvents were evaporated under vacuum. The obtained yellow oily product was washed throughly with chloroform and ether. After drying for 6 h under vacuum at 80 °C, the expected ionic liquid was obtained as yellow oil (Fig 2.28).

Fig 2.28. 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2-aeeim]BF 4

[2-aeeim]BF 4 (1c) : Yellow oil; 7.6 g (yield, 67 %). Anal. Calcd. for C7H14 F4N3B (227): C, 37.04; H, 6.22; N, 18.51. Found: C, 37.02; H, 6.12; N, 18.38 %. FT- IR (KBr, cm -1): 3447 (N-H), 3086, 2896, 1626 (C=N), 1452, 1084 (B-F); 1H NMR (400

MHz, D2O) δ : 336 (m, 2H, NH 2-CH2), 3.40 (t, 1H, N-CH2), 4.16 (s, 3H, C H3), 4.50

(t, 1H, N-CH2), 7.40 (s, 1H, NC H), 7.50 (s, 1H, NC H), 8.61 (s, 2H, N H2), 8.87 ( s, 1H, 13 N( H)CN). C NMR (400 MHz, D2O) δ: 123, 122.50, 119.85, 49.02, 45.55, 45.24 and + 1 13 44.64. ESI-MS (CH 3OH, m/z ): 140 ([M-BF 4] ). The H NMR, C NMR, FT-IR and ESI-MS spectra are given below.

Experimental Section

Fig 2.29 . FT-IR spectrum of [2-aeeim]BF 4.

1 Fig 2.30. H NMR spectrum of [2-aeeim]BF 4.

Experimental Section

13 Fig 2.31. C NMR spectrum of [2-aeeim]BF 4.

Fig 2.32. ESI-MS spectrum of [2-aeeim]BF 4.

Experimental Section

2.2.4.4. Synthesis of 1-(2-aminoethyl)-3-methyllimidazolium tetrafluoroborate, [2-aemim]BF 4 (1d) This amine functionalized ionic liquid was prepared by following the same procedure [6] as mentioned above. In this reaction, 1-methylimidazole (4.10 g,

0.05mol), 2-bromoethylamine hydrobromide (10.25 g, 0.05mol) and NaBF 4 (5.5 g, 0.05 mol) were used. The product was obtained as yellow oil (Fig 2.33).

Fig 2.33. 1-(2-aminoethyl)-3-methyllimidazolium tetrafluoroborate, [2-aemim]BF 4

[2-aemim]BF 4 (1d ): Yellow oil; 7.56 g (yield, 71 %). Anal. Calcd. for

C6H12 F4N3B (213): C, 33.84; H, 5.68; N, 19.73. Found: C, 33.58; H, 5.42; N, 19.65 %. FT-IR (KBr, cm -1): 3439 (N-H), 2369, 2055, 1634 (C=N), 1297, 1087 (B-F). 1H

NMR (400 MHz, D2O) δ: 3.22 (t, 2H, NH 2-CH2); 4.23 (s, 3H, C H3), 4.43 (t, 1H, N-

CH2), 7.42 (s, 1H, NC H), 7.49 (s, 1H, NC H), 8.67 (s, 2H, N H2), 8.75 (s, 1H, 13 N( H)CN); C-NMR (400 MHz, D2O) δ: 137.07, 124.28, 122.33, 54.37, 39.58, 37.53. + 1 13 ESI-MS (CH 3OH, m/z ): 126.20 [(M-BF4) ]. The H NMR, C NMR, FT-IR and ESI- MS spectra are given below.

Experimental Section

Fig 2.34. FT-IR spectrum of [2-aemim]BF 4.

Fig 2.35. ESI-MS spectrum of [2-aemim]BF 4.

Experimental Section

Scheme 2.2. Synthesis of FILs ( 1b ), ( 1c ) and ( 1d ).

References [1] Clinical and Laboratory Standards Institute (NCCLS), Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, 9 th ed. M2-A9, Wayne, PA, 2006. [2] Clinical and Laboratory Standards Institute (NCCLS) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard, 7 th ed. M7-A7, Wayne, PA, 2006. [3] P.W. Su, C.H. Yang, J.F. Yang, P.Y. Su, L.Y. Chuang, Molecules., 20(6) (2015) 11119. [4] C. Valgas, S.M.D. Souza, E.F. Smânia, Jr. A. Smânia., Brazilian journal of microbiology, 38(2) (2007) 369. [5] https://books.google.co.in/books. [6] Y. Hua, S. Huab, F. Li, Y. Jianga, X. Baib, D. Li, L. Niua, Biosensors and Bioelectronics. 26 (2011) 4355. [7] G. Song, Y. Cai, Y. Peng, J. Comb. Chem . 7 (2005) 561.

CHAPTER III

Synthesis, characterization and antibacterial studies of Mn(II) and Co(II) complexes of an ionic liquid supported Schiff base: [1-{2-(2-hydroxybenzylideneamino)ethyl}-3-methyl-1H imidazolium] bromide *

3.1. Introduction Ionic liquids (ILs) are generally based on inorganic or organic anions paired with large, usually asymmetric organic cations, have low melting points below 373 K although many are in fact liquid at/below ambient temperature [1, 2]. They are worthy of extensive investigation because of their unique physical and chemical properties such as nonvolatile, nonflammable, thermally stable and recyclable. In addition to the properties just mentioned, ILs exhibit a wide electrochemical window, high ionic conductivity, a broad temperature range of the liquid state and frequently possess excellent chemical inertness as well [3-5]. The hydrophobicity/hydrophilicity and other physical features of ionic liquids including density, melting point, conductivity, polarity, Lewis acidity, viscosity, enthalpy of vaporization can be altered by manipulating the structure of cations and anions [6] and issues such as their toxicity and biodegradability are now being researched to judge them as potentially green replacements for traditional molecular solvents [7]. To date, ILs have been used in organic synthesis, catalysis, industrial processing, electrochemistry, pharmaceutics, biotechnology, nano-chemistry, analytical chemistry and separation technology. Ionic liquids shaped for a particular function are referred to functionalized ionic liquids (FILs). Recently, much attention has been paid to the preparation and application of FILs with special tasks, such as carrying hydroxyl, amino, sulfonic acid, carbonyl, etc [8-12]. The increasing popularity of the FILs lies in the fact that both the cationic and anionic parts can be altered and applied to a specific application. Again, the incorporation of functional groups can exhibit a particular capability to the ILs by increasing catalytic stability and reducing catalytic leaching [12, 13]. Imidazolium

*Published in J. Serb. Chem. Soc., 81 ( 2016 ) 1151–1159.

Chapter III based systems play important roles in biochemical processes [14] for having varied pharmacological properties. Schiff bases and their metal complexes play a significant role in the field of coordination chemistry and have been studied extensively because of their remarkable chemical and physical properties. The azomethine linkage in the structures of Schiff bases has been ascribed for their biological actions like antibacterial and analytical activities [15, 16]. Particularly transition metal complexes of Schiff bases with oxygen and nitrogen donors are of particular interest, [17] because of their ability to possess unusual configuration and structure-related bioactivities [18, 19]. Hence in this chapter the synthesis and physico-chemical characterizations of an imidazolium ionic liquid-supported Schiff base, [1-{2-(2- hydroxybenzylideneamino)ethyl}-3-methyl-1H imidazolium] bromide and its Mn(II) and Co(II) complexes were reported. The synthesized Schiff base ligand and metal complexes were tested for in vitro antibacterial activity against two commonly known gram negative bacteria Escherichia coli and gram positive bacteria Bacillus subtilis. 3.2. Experimental Section 3.2.1. Materials and Methods All the reagents were of analytical grade and used without further purification. 1-methyl imidazole and 2-bromoethylamine hydrobromide were procured from Sigma

Aldrich, Germany. Salicylaldehyde, Mn(OOCCH 3)2.4H 2O, Co(OOCCH 3)2.4H 2O and all other chemicals were used as received from SD fine Chemicals, India. The solvents methanol, petroleum ether, chloroform, DMF and DMSO were used after purification by the standard methods describe in the literature. The amino functionalized ionic liquid, 1-(2-aminoethyl)-3-methylimidazolium bromide, [2- aemim]Br (1a ) was synthesized by following a literature procedure [20]. The synthesis and physicochemical characterization of the ionic liquid have been described earlier in chapter II. FT-IR spectra were recorded in KBr pellets with a Perkin-Elmer Spectrum FT- IR spectrometer (RX-1) operating in the region 4000 to 400 cm -1. 1H-NMR spectra were recorded at room temperature on a FT-NMR (Bruker Advance-II 400 MHz) spectrometer by using DMSO-d6 and D 2O as solvents. Chemical shifts are quoted in ppm downfield of internal standard tetramethylsilane (TMS). Elemental micro-

Chapter III analyses (C, H and N) were conducted by using Perkin–Elmer (Model 240C) analyzer. Metal contents were determined with the aid of AAS (Varian, SpectrAA 50B) by using standard metal solutions from Sigma-Aldrich, Germany. Mass spectra were recorded on a JMS-T100LC spectrometer. The purity of the synthesized compounds was checked by thin layer chromatography (TLC) on silica gel plates. The UV-Visible spectra were recorded in methanol with a JascoV-530 Spectrometer. Magnetic susceptibilities were measured at room temperature with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1). Molar conductance was measured with a Systronics conductivity TDS meter (Model- 308) with a cell (Type CD -30, cell constant 0.10±10%) at (298.15±0.01) K. Antibacterial activities ( in vitro ) of the synthesized ligand and the complexes were studied by disc diffusion method against two bacteria, viz. , Bacillus subtilis. and Escherichia coli. with respect to the standard drug Ampicilin. 3.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2a) A mixture of salicylaldehyde (1.22 g, 10 mmol) and [2-aemim]Br (2.06 g, 10 mmol) was stirred at room temperature for 12 h without a solvent, followed by washing with diethyl ether (3 × 30 mL) and vacuum evaporation which gave the product as brown oil: 2.11g (yield: 68%). Anal. Calcd. for C 13 H16 N3OBr (310): C, 50.34; H, 5.20; N, 13.55. Found: C, 50.11; H, 5.09; N, 13.20 %; FT-IR (KBr, cm -1): 3429 (O-H), 3143, 1626 (C=N), 1579, 1454 (C-O), 1279, 623 (C-Br); 1H-NMR: (400

MHz, DMSO-d6): δ 3.95 (s, 3H, C H3), 4.68 (t, 1H, N-CH2), 4.58 (t, 1H, N-CH2), 7.83–7.72 (m, 4H, Ar-H), 6.98 (s, 1H, NC H), 6.95 (s, 1H, NC H), 9.20 (s, 1H, 13 N=C H), 9.29 (s, 1H, N( H)CN), 8.31 (s, 1H, O H). C-NMR: (400 MHz, DMSO-d6): δ 136.98, 136.36, 135.07, 124.58, 123.93, 123.13, 122.55, 119.58, 53.46, 52.77, + + 50.93, 36.38 and 35.86. ESI-MS (CH 3OH, m/z ) 230, [(M-Br) , M= (C13 H16 N3O) ]. 3.2.3. Synthesis of the metal complexes (3a and 4a) To an ethanolic solution (20 mL) of ligand, LH (0.50 g, 1.30 mmol), metal acetate, viz. , Mn(CH 3COO) 2.4H 2O (0.173 g, 0.65 mmol) or Co(CH 3COO) 2.4H 2O (0.16 g, 0.65 mmol) dissolved in ethanol was added and the mixture was refluxed for 8 h until the starting materials were completely consumed as monitored by TLC. On completion of the reaction, solvent was evaporated and the reaction mixture was cooled to room temperature.

Chapter III

The precipitate was filtered, washed with ethanol (10 mL × 3) and dry ether (10 mL × 3), respectively and finally dried in a desiccator to obtain the solid product. The complexes are soluble in N, N -dimethylformamide, dimethylsulphoxide, acetonitrile and methanol. A schematic representation of the synthesis was shown in Scheme 3.1.

Scheme 3.1. Synthesis of the ionic liquid-supported Schiff base, [1-{2-(2- hydroxybenzylideneamino)ethyl}-3-methyl-1H imidazolium] bromide (2a ), and M(II) complexes ( 3a and 4a ) from ( 2a ).

3.2.2.1. Mn(II) complex (3a): Brown solid; 0.59 g (yield, 67 %). Anal. Calc. for C26 H30 MnN 6O2Br 2 (673): 46.38; H, 4.49; N, 12.48; Mn, 8.16. Found: C, 46.22; H, 4.43; N, 12.36; Mn, 8.06; FT-IR (KBr, cm -1): 3398 (O-H), 1616 (C=N), 1444 (C-O), 756 (Br), 565 (M-O), 460 (M-N). UV-Vis (Methanol) λmax/nm: 211, 255, 314. ESI- + + MS (CH 3OH, m/z): 513 ([M-2Br] , M= [C 26 H30 MnN 6O2] ). 3.2.2.2. Co(II) complex (4b): Dark brown solid; 0.60 g (yield, 68 %). Anal.

Calc. for C26 H30 CoN 6O2Br 2 (677.30): C, 46.11; H, 4.46; N, 12.41; Co, 8.20. Found: C, 46.02; H, 4.33; N, 12.39; Co, 8.10; FT-IR (KBr, cm -1): 3423 (O-H), 1601 (N-H), 1449 (C-O), 761 (Br), 590 (M-N), 475 (M-O). UV-Vis (Methanol) λmax/nm: 220, + + 248, 403. ESI-MS (CH 3OH, m/z ) 517 ([M-2Br] , M= [C 26 H30 MnN 6O2] )].

Chapter III

3.3. Results and Discussion The complexes are moisture sensitive, stable in vacuum desiccator and soluble in N, N -dimethylformamide, dimethylsulphoxide, acetonitrile and methanol. All the isolated compounds were found to be hygroscopic in nature and were characterized by different analytical and spectroscopic methods. 3.3.1. FT-IR spectral studies FT-IR spectra of the complexes ( 3a and 4a ) were compared to that of the free ligand in order to determine the coordination sites involved in the complexation. The ligand showed a strong broad band at 3429-3143 cm -1; this band was attributed to the hydrogen bonded -OH of the phenolic group with H–C(=N) group of the ligand (OH…N=C) [21]. The broad band appeared in the range 3398-3423 cm -1 in the spectra of Mn(II) and Co(II) complexes, respectively were due to absorption of water molecules as reported Gruzdev et al [22]. The band at 1454 cm -1 was observed for phenolic -CO of the free ligand shifted to lower frequency region 1444-1449 cm -1 for the complexes [23] on chelation. In the ligand a band corresponding to the azomethine group (-C=N) was found at 1626 cm -1. On complexation, this band gets shifted to the range of 1616-1601 cm -1. This indicated the involvement of N-atom of azomethine (- C=N) group in the complex formation [24]. Therefore IR spectra suggested that the ligand ( 2a ) coordinateed to metal ions (Mn 2+ and Co 2+ ) through the N- atom of azomethine (-C=N) group and the O-atom of phenolic (O-Ar) group. The peak at the range of 756-761 cm -1 in the spectra of complexes, was assigned for bromide. The new bands appearing in the regions 565-590 cm -1 and 460-475 cm -1 in the spectra of 3a and 4a complexes could be assigned to M-O and M-N stretching frequencies, respectively [25]. FT-IR spectra of the Schiff base, LH ( 2a ) and its Mn(II) and Co(II) complexes ( 3a and 4a ) are given in Figs 3.1-3.3.

Chapter III

Fig 3.1. FT -IR spectrum of LH ( 2a ).

Fig 3.2. FT -IR spectrum of Mn(II) complex ( 3a ).

Chapter III

Fig 3.3. FT -IR spectrum of Co(II) complex ( 4a ) .

3.3.2. Mass spectral studies The mass spectra of the ligand ( 2a) showed a molecular ion peaks ( m/z ) at + + 230, which was assigned to M , [C 13 H16 N3O] ion peak. The Mn(II) complex ( 3a ) + + exhibited a peak ( m/z ) at 513 which was due to [M-2Br] (M= [C26 H30 MnN 6O2] ) ion. A peaks ( m/z ) at 517 in the ESI-MS spectrum of Co(II) complex (4a ) attributed to the + + at [M-2Br] (M= [C26 H30 CoN 6O2] ).ion. The different molecular ion peaks, observed in the mass spectra of the Mn(II) and Co(II) complexes, were assigned to different fragmentations of the metal complexes by successive rupture of different bonds in order to form stable ions. The ESI-MS spectra of the ligand and complexes are shown in Figs 3.4-3.6.

Chapter III

Fig 3.4 . ESI-MS spectrum of LH ( 2a ).

Fig 3.5 . ESI-MS spectrum of Mn(II) complex ( 3a ).

Chapter III

Fig 3.6. ESI-MS spectrum of Co(II) complex (4a ).

3.3.3. 1H and 13 C-NMR spectral studies 1H-NMR and 13 C-NMR spectra of Schiff base ( LH ) were recorded in DMSO- 1 d6 (Shown in Fig 3.7 and Fig 3.8.). H-NMR of the LH ( 2a ) showed singlet at 9.20 ppm assignable to proton of the azomethine group (-CH=N-) probably due to the effect of the ortho -hydroxyl group in the aromatic ring. A singlet at 8.31 ppm can tentatively be attributed to hydroxyl proton. The LH ( 2a ) showed downfield shift of the –OH proton was due to intramolecular (O-H...N) hydrogen bond [26]. 13 C-NMR spectra of ligand exhibited peaks at δ 136.98 and 136.36 presumably due to the phenolic (C-O) and imino (-CH=N) carbon atoms (due to Keto-imine tautomerism). The chemical shifts due to the aromatic carbons appeared at δ 124.58, 123.13, 122.55 and 119.58.

Fig 3.7. 1H-NMR spectrumof LH ( 2a ).

3.3.4. Molar conductance measurements

The molar conductance of the complexes ( 3a and 4a) (Λm) were obtained from the relation Λm = 1000 × κ/c, where c and κ stand for the molar concentration and specific conductance of the metal complexes, respectively. The complexes (1.8 × 10 −3 M) were dissolved in N, N -dimethylformamide and their specific conductivities were measured at 25 oC. The molar conductances were found to be in the range 212-238 Ω- 1 cm -1 mol -1 indicating their 1:2 electrolytic behaviour [27].

Chapter III

Fig 3.8. 13 C-NMR spectrum of LH ( 2a ).

3.3.5. Electronic absorption spectral and magnetic moment studies UV-Visible spectra of the Schiff base ( 2a ) and its metal complexes (Given in Fig 3.9) were recorded in methanol at ambient temperature. The electronic absorption spectrum of ligand showed three absorption bands at 318, 255 and 214 nm, respectively due to n →π*, π→π * transitions and transitions involved with the imidazolium moiety [28, 29]. Mn(II) complex ( 3a ) showed three absorption bands at 314, 255 and 211 nm; that was the ligand band at 318 nm showed hypsochromic shift probably due to coordination with Mn 2+ (d 5) ion. Co(II) complex ( 4a ) also displayed 4 4 4 4 three absorption bands at 220, 248 and 403 nm due to A2→ T1(P), A2→ T1(F) and 4 4 A2→ T2 transitions, respectively. Thus UV-Visible spectra of both the complexes ( 3a and 4a ) suggested no Jahn-Teller distortion and tetrahedral geometry was proposed for both the complexes [30].

Chapter III

Fig 3.9. UV-visible spectra in methanol (concentration of the solutions 1 × 10-4 M): (A) LH ( 2a ); ( B) Mn(II) complex ( 3a ) and ( C) Co(II) complex ( 4a ).

This fact was also substantiated by the results obtained from FT-IR, ESI-MS, UV- Visible spectra and the measured magnetic moments (5.86 and 4.67 B.M, respectively for 3a and 4a complex). 3.3.6. Antibacterial activities The Schiff base ligand ( 2a ) and their metal complexes ( 3a and 4e ) were studied against the gram negative bacteria Escherichia coli and gram positive bacteria Bacillus subtilis. to assess their potentials as antibacterial agents. Stock solutions of synthesised compounds were prepared by dissolving the compounds in water and serial dilutions of the solutions were made in sterile distilled water for different concentrations to determine the minimum inhibition concentration (MIC). The concentrations of the tested compounds were 31.25, 62.5, 125 and 250 µg mL -1 in comparison to the standard drug Ampicilin. The nutrient agar medium was poured into 0.5 mL culture contained in Petri dishes and well diffusion technique [31, 32] was

Chapter III performed. Petri dishes were placed in an incubator at 37 oC for 24 h. No significant inhibition zones surrounding the well were observed against the complexes (minimum

Fig 3.10 . Inhibition zones for anti-bacterial activities: A, LH (2a ); B; the Mn(II) complex ( 3a ); C, the Co(II) complex ( 4a ) against Escherichia Coli . inhibition concentration against Escherichia coli was shown in Fig 3.10), but the ligand showed very low antibacterial activities with well diameters in the range of 1.0-1.2 mm at the concentration 250 µg mL -1 against the bacteria studied. 3.4. Conclusion Here in this work, the synthesis and physico-chemical characterization of an imidazolium ionic liquid-supported Schiff base, i.e ., 1-{2-(2- hydroxybenzylideneamino)ethyl}-3-methylimidazolium bromide, and its Mn(II) and Co(II) complexes were described. Different analytical and spectral studies revealed that the Schiff base acts as bidentate ligand that coordinated through the azomethine nitrogen and phenolic oxygen atoms to Mn(II) and Co(II) ions and thus formed tetrahedral 1:2 (M:L) complexes. The synthesized compounds were tested for their antibacterial activities against the bacteria Escherichia coli and Bacillus subtilis . The observed minimum inhibition (MIC) concentration, suggested that the synthesized complexes have no significant antibacterial activities against the bacteria Escherichia coli and Bacillus subtilis .

Chapter III

References [1] S.A. Forsyth, J.M. Pringle, D.R. MacFarlane, Aust. J. Chem., 57 (2004) 113. [2] D.R. MacFarlane, K.R. Seddon, Aust. J. Chem., 60 (2007) 3. [3] P. Wasserscheid, W. Keim, Angew. Chem., Int., Ed. 39 (2000) 3773. [4] B. Singh, S.S. Sekhon, Chem. Phys. Lett., 414 (2005) 34. [5] A. Noda, M. Watanabe, Electrochim. Acta., 45 (2000) 1265. [6] U. Doma ńska, R. Bogel-Łukasik, J. Phys. Chem. B., 109 (2005) 12124. [7] C.C. Tzschucke, C. Markert, W. Bannwarth, S. Roller, A. Hebel, R. Haag, Angew. Chem., Int., Ed. 41 (2002) 3964. [8] J.H. Davis Jr., Chem. Lett., 33 (2004) 1072. [9] F. Yi, Y. Peng, G. Song, Tetrahedron Lett., 46 (2005) 3931. [10] J. Li, Y. Peng, G. Song, Catal. Lett., 102 (2005) 159. [11] J.H. Davis Jr., K. J. T. Forrester, J. Merrigan, Tetrahedron Lett., 49 (1998) 8955. [12] J.J. Jodry, K. Mikami, Tetrahedron Lett., 45 (2004) 4429. [13] S.G. Lee, Chem. Commun., 14 (2006) 1049. [14] J.G. Lambardino, E.H. Wiesman, J. Med. Chem., 17 (1974) 1182. [15] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 235. [16] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 1384. [17] N.E. Borisova, M.D. Reshetova, Y A. Ustynyuk, Chem. Rev., 107 (2007) 46. [18] A. Goku, M. Tumer, H. Demirelli, R.A. Wheatley, Inorg. Chim. Acta., 358 (2005) 1785. [19] A.M. Mahindra, J.M. Fisher, Rabinovitz, Nature., 303 (1983) 64. [20] Y. Hua, S. Huab, F.Li, Y. Jianga, X. Baib, D.Li, L. Niua, Biosensors and Bioelectronics., 26 (2011) 4355. [21] G.-Y. Yeap, S.-T. Ha, N. Ishizawa, K. Suda, P.-L. Boey, W.A.K. Mahmood, J. Mol. Struct., 658 (2003) 87. [22] M.S. Gruzdev, L.M. Ramenskaya, U.V. Chervonova, R.S. Kumeev, Russian Journal of General Chemistry.,79 (2009) 1720. [23] E. Canpolat, M. Kaya, Turk. J. Chem., 29 (2005) 409. [24] G.A. Kohawole, K.S. Patel, J. Chem. Soc., Dalton Trans., 6 (1981) 1241.

Chapter III

[25] D.M. Adams, Metal-Ligand and Related Vibrations: A Critical Survey of the Infrared and Raman Spectra of Metallic and Organometallic Compounds, Edward Arnold (Publishers) Ltd London, England, 1967. [26] Z. Popovic, V. Roje, G. Pavlovic, D.M. Calogovic, G. Giester, J. Mol. Struct. 597 (2001) 39. [27] W.J. Geary, Coord. Chem. Rev., 7 (1971) 81. [28] R.M. Silverstein, F.X. Webster, Spectrometric Identification of Organic Compounds, 6 th ed., Wiley India Pvt. Ltd., New Delhi, 2014. [29] F. Peral, E. Gallego, J. Mol. Struc., 415 (1997) 187. [30] A.P. Lever, Inorganic Electronic Spectroscopy, 2 nd ed., Elsevier, New York, 1984. [31] Clinical and Laboratory Standards Institute (NCCLS) Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, 9 th ed., M2-A9, Wayne, PA, 2006. [32] Clinical and Laboratory Standards Institute (NCCLS) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard, 7 th ed., M7-A7, Wayne, PA, 2006.

CHAPTER IV

Mn(II), Co(II) and Cu(II) complexes of an ionic liquid-supported Schiff base, [1-{2-(2-hydroxybenzylideneamino)ethyl}-3-methyl imidazolium]PF 6: Synthesis, Physico-chemical characterization and biological activities *

4.1. Introduction Ionic liquids (ILs) are defined as organic salts formed by the combination of bulky organic cations with a wide variety of anions that are generally liquid at room temperature [1]. ILs are made up of large ions that are held together by electrostatic interactions. Due to these interactions, the properties of ILs are considerably different from those of molecular liquids [2]. ILs have been widely studied as alternatives to volatile organic solvents for organic synthesis in homogeneous as well as biphasic processes [3-5]. Such compounds have received attraction in synthetic chemistry in recent years due to their excellent characteristics, such as low vapour pressure, inflammability, high thermal and chemical stability, outstanding solubility and the possibility of easy recycling, etc [6, 7]. Based on these properties, ILs have emerged as a novel class of compounds that have been employed in many fields, such as electrochemistry, organic synthesis, catalysis, gas separation, etc . The use of ionic liquids has also received much attention as eco-friendly reaction media in organic synthesis [5, 8]. The hydrophobicity/hydrophilicity of ionic liquids can be altered by manipulating the structures of the cations and anions [9]. In recent years, a number of ionic liquids have been identified as solvents for the dissolution of biopolymers such as cellulose, starch, wood, lignin, feather, wool, etc [10–17]. Recently, many workers have focused on the preparation and application of functionalized ionic liquids (FILs) for special tasks, such as those carrying hydroxyl, amino, sulfonic acid or carboxyl groups and so on [18–24]. The FILs have shown great promise not only as alternative green solvents, but also as reagents or catalysts in many organic transformations [25]. Among many potential organic compounds, Schiff bases are widely employed as ligands in coordination chemistry [26]. These ligands are readily available, versatile and, depending on the nature of the starting materials (primary amines and carbonyl 68

Chapter IV precursors), they exhibit various denticities and functionalities [27]. Schiff bases and their complexes are widely applied in biochemistry, material science, catalysis, encapsulation, activation, transport and separation phenomena, hydrometallurgy, etc [28, 29]. Schiff bases have been reported to show a variety of biological actions, such as antibacterial, antifungal, herbicidal, clinical and analytical activities by virtue of the azomethine linkage [30, 31]. Schiff base metal complexes have been the subject of intensive study due to their industrial and biological applications [32–37]. Salicylaldehyde and its derivatives are useful carbonyl precursors for the synthesis of a large variety of Schiff bases with wide variety of interesting properties. Hence in this chapter, an attempt was made to synthesize an ionic liquid supported Schiff base 1-{2-[(2-hydroxybenzylidene)amino]ethyl}-3- methylimidazolium hexafluorophosphate, and its Mn(II), Co(II) and Cu(II) complexes. The synthesized compounds were characterized by various analytical techniques and tested for their biological activities against gram positive / negative bacteria. 4.2. Experimental Section 4.2.1. Materials and Methods All the reagents were of analytical grade and used without further purification. 1-methyl imidazole, 2-bromoethylamine hydrobromide and potassium hexafluorophosphate were procured from Sigma Aldrich, Germany. Salicylaldehyde,

Metal acetates [Mn(CH 3COO) 2, 4H 2O, Co(CH 3COO) 2, 4H 2O and Cu(CH 3COO) 2,

H2O] and all other chemicals were purchased from SD fine Chemicals, India and used as received. The solvents methanol, petroleum ether, chloroform, DMF and DMSO were used after purification by the standard methods describe in the literature. The

FIL, 1-(2-aminoethyl)-3-methylimidazolium tetrafluorophosphate, [2-aemim]PF 6 (1b ) was synthesized by following a literature procedure [38]. The synthesis and physicochemical characterization of the ionic liquid have been illustrated earlier in chapter II. FT-IR spectra were recorded in KBr pellets with a Perkin-Elmer Spectrum RX-I FT-IR spectrometer, operating in the region 4000 to 400 cm -1. 1H-NMR and 13 C-NMR spectra were recorded at room temperature on a FT-NMR BRUKER

ADVANCE II 400 MHz spectrometer by using DMSO-d6 and D 2O as solvents.

Chapter IV

Chemical shifts are quoted in ppm downfield of internal standard tetramethylsilane (TMS). Melting points were recorded by open capillary method. Elemental microanalyses (C, H and N) were conducted by using Perkin–Elmer (Model 240C) analyzer. Metal content was determined with the aid of AAS (Varian, SpectrAA 50B) by using standard solution from Sigma-Aldrich, Germany. Mass spectra were recorded on a Agilent 1100 LC equipped with an MSD trap. The purity of the Schiff base and its complexes were confirmed by thin layer chromatography (TLC) on silica gel plates and TLC visualization was done by UV-light and iodine. Antibacterial activities ( in vitro ) of the synthesized ligand and the complexes were studied by disc diffusion method against commonly known bacteria, viz. , Bacillus subtilis and Escherichia coli . with respect to the standard drug Ampicilin .

4.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2b) The ionic liquid supported Schiff base ligand (LH) was synthesized by slight modification of a literature procedure [39]. A mixture of Salicylaldehyde (1.22 g, 10 mmol) and [2-aemim]PF 6 (2.71 g, 10 mmol) in 10 mL methanol was taken in a round bottomed flask equipped with air condenser and stirred at room temperature for 12 h. After completion of the reaction, as indicated by TLC, the reaction mixture was diluted with methanol (10 mL). The precipitate was then filtered, washed with cold ethanol and dried to afford the expected ligand as a pale yellow solid: 2.6 g (yield: 70

%); M. p. 132-133 ºC, Anal. Calcd. for C 13 H16 N3OPF 6 (375): C, 41.61; H, 4.30; N, 11.20. Found: C, 40.81; H, 4.19; N, 10.99 %. FT-IR (KBr, cm -1): 3430 (O-H), 1640 1 (C=N), 1278 (C-O), 837 (P-F); H NMR (400 MHz, DMSO-d6): δ 3.40 (s, 3H, C H3),

4.52 (t, 2H, N-CH2), 4.63 (t, 2H, N-CH2), 7.71–7.89 (m, 4H, Ar-H), 7.94 (s, 1H, NC H), 8.07 (s, 1H, NC H), 9.17 (s, 1H, N=C H), 9.31 (s, 1H, N( H)CN), 8.23 (s, 1H, 13 OH); C-NMR (400 MHz, DMSO-d6): δ 135.95, 135.87, 133.92, 123.00, 122.95, 122.40, 121.45, 119.55, 53.39, 52.69, 50.82, 38.89, 35.46. UV-Vis (Methanol) + + λmax/nm: 217, 248, 334. ESI-MS (CH 3OH, m/z): 230 ([M-PF 6] , M= [C 13 H16 N3O] ). 4.2.3. Synthesis of the metal complexes (3b, 4b and 5b) The ligand, ( 2b ) (0.50 g, 1.30 mmol) was taken in a round bottomed flask and dissolved in EtOH (20 mL). Solution of ethanolic metal acetate salt Mn(II), Co(II) and Cu(II)), viz. , (0.65 mmol) was added and the reaction mixture was refluxed for 4 hours until the starting materials were completely consumed as monitored by TLC.

Chapter IV

Solvents were evaporated and the reaction mixture was brought to room temperature. The precipitate was collected by filtration, washed successively with cold ethanol. The product was dried in vacuum desiccator to obtain the solid product. The complexes are soluble in N,N-dimethylformamide, dimethylsulphoxide, and methanol. The reaction scheme is shown in Scheme 4.1.

Scheme 4.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-[(2- hydroxybenzylidene)amino]ethyl}-3-methylimidazolium hexafluorophosphate (2b ), and its metal complexes ( 3b, 4b and 5b ) from ( 2b ).

4.2.2.1. Mn(II) complex ( 3b): Brown solid; 0.67 g (yield, 65 %) M. p.: 162- o 164 C; Anal. Calc. for C26 H30 MnF 12 N6O2P2 (803.42): C, 38.87; H, 3.76; N, 10.46; Mn, 6.84. Found: C, 38.46; H, 3.56; N, 10.32, Co, 6.49 %. FT-IR (KBr, cm -1): 3448 (O-H), 1635 (C=N), 1281 (C-O), 838 (P-F), 620 (M-O), 558 (M-N). UV-Vis + (Methanol) λmax/nm: 210, 254, 318. ESI-MS (CH 3OH, m/z): 515 ([M+2H-2PF 6] , + M= [C 26 H30 MnN 6O2] ). 4.2.2.2. Co(II) complex (4b): Dark brown solid; 0.71 g (yield, 68 %). M. p. o 157-159 C; Anal. Calc. for C26 H30 CoF 12 N6O2P2 (807.42): C, 38.68; H, 3.75; N, 10.41; Co, 7.30. Found: C, 38.41; H, 3.59; N, 9.97, Ni, 7.13 %. FT-IR (KBr, cm -1): 3423 (O-H), 1637 (C=N), 1309 (C-O), 842 (P-F), 622 (M-O), 558 (M-N). UV-Vis + (Methanol) λmax/nm: 211, 249, 334, 390. ESI-MS (CH 3OH, m/z): 516 ([M-H-2PF 6] , + M= [C26 H30 CoN 6O2] ). 4.2.2.3. Cu(II) complex (5b): Dark green solid; 0.70 g (yield, 67 %). M. p. o 167-169 C; Anal. Calc. for C26 H30 CuF 12 N6O2P2 (812): C, 38.46; H, 3.72; N, 10.35; Cu, 7.83. Found: C, 38.01; H, 3.69; N, 10.11; Cu, 7.56 %. FT-IR (KBr, cm -1): 3423 (O-H), 1633 (C=N), 1314 (C-O), 843 (P-F), 621 (M-O), 559 (M-N). UV-Vis

Chapter IV

+ (Methanol) λmax/nm: 220, 337, 397. ESI-MS (CH 3OH, m/z): 524 ([M+3H-2PF 6] , + M= [C26 H30 CuN 6O2] ). 4.2.4. Antibacterial Activity The newly synthesized metal complexes along with the ligand were tested against the gram-negative bacterium Escherichia coli (ATCC 69905) and the gram- positive bacterium Bacillus subtilis (ATCC 6633) . Stock solutions of compounds were prepared by dissolving the compounds in distilled water and serial dilutions of the compounds were prepared in sterile distilled water for different concentrations to determine the minimum inhibition concentration (MIC). The concentrations of the tested compounds were 31.25, 62.5, 125 and 250 µg/mL in comparison to the standard drug Ampicillin. The nutrient agar medium was poured into 0.5 mL culture containing Petri plates. Then the well diffusion technique [40, 41] was performed. Petri plates were incubated at 37 °C for 24 h. 4.3. Results and Discussion All the isolated compounds were found to be air stable and were characterized on the basis of elemental and different spectroscopic analysis. 4.3.1. FT-IR spectral studies In order to have a conclusive idea about the coordination mode of the ligand (2b ) to the metal ion and structure of the metal complexes, the main IR bands of metal complexes were compared with those of the ligand. FT-IR spectra of the ligand showed a strong broad absorption band at 3430.12-3151 cm -1; this band was assigned to the hydrogen bonded -OH of the phenolic group with H–C(=N) group of the ligand (OH…N=C) [42, 43]. The complexes ( 3b , 4b and 5b ) showed broad band at 3423- 3448 cm -1 which could be assigned to the presence of the hydrated water or ethanol molecules. The band for phenolic C-O of free ligand was observed at 1278 cm -1. Upon complexation, this band was shifted to higher wave number 1281-1314 cm -1 for all the complexes. This fact suggested the involvements of phenolic C-O in the coordination process [44]. This interpretation was further confirmed by the appearance of M-O band at 620-622 cm -1 in the spectra of the metal complexes. In the ligand a band corresponding to the azomethine group (-C=N) was found at 1640 cm -1. On complexation, this band shifted to lower wave number range of 1633-1637 cm -1. This indicated the involvement of N- atom of azomethine (-C=N) group in the

Chapter IV complex formation [45]. This was further established by the appearance of a new weak to medium intensity absorption band in the region 558-559 cm -1 that was due to M-N stretching vibration for the metal complexes [46]. The bands in the range of 838- 845 cm -1 for the spectra of the ligand and metal complexes were assigned for P-F stretching frequency. The IR spectra of the free Schiff base ( 2b ) and its metal complexes ( 3b , 4b and 5b ) are given in Figs 4.1-4.4.

Fig 4.1. FT -IR spectrum of LH ( 2b ).

Fig 4.2. FT -IR spectrum of Mn(II) complex ( 3b ).

Chapter IV

Fig 4.3. FT -IR spectrum of Co(II) complex ( 4b ).

Fig. 4.4. FT -IR spectrum of Cu(II) complex ( 5b ).

4.3.2. Mass spectral studies The mass spectra of the ligand, ( 2b ) showed a molecular ion peaks ( m/z ) at + + 230, which was assigned to [M-PF 6] , M= [C 13 H16 N3O] ion. The Mn(II) complex + (3b ) displayed a peak ( m/z ) at 515 which was due to [M-2H-2PF 6] (M=

Chapter IV

+ [C26 H30 MnN 6O2] ) ion. A peaks ( m/z ) at 516 in the ESI-MS spectrum of Co(II) + + complex ( 4b ) was assigned for the [M-2PF 6] (M= [C26 H30 CoN 6O2] ).ion. The ESI- MS spectrum of Cu(II) complex ( 5b ) exhibited a peak ( m/z ) at 524 which was + + detected for [M+3H-2PF 6] (M= [C26 H30 CuN 6O2] ) ion. The different molecular ion peaks, appeared in the mass spectra of the complexes, were attributed to different fragmentations of the metal complexes by successive rupture of different bonds in order to form stable ions. The ESI-MS spectra of the ligand and complexes are shown in Figs 4.5-4.8.

Fig 4.5 . ESI-MS spectrum of LH ( 2b ).

Chapter IV

Fig 4.6 . ESI-MS spectrum of Mn(II) complex ( 3b ).

Fig 4.7. ESI-MS spectrum of Co(II) complex ( 4b ).

Chapter IV

Fig 4.8 . ESI-MS spectrum of Cu(II) complex ( 5b ).

4.3.3. 1H and 13 C-NMR spectral studies The 1H-NMR and 13 C-NMR spectra of Schiff base ( 2b ) were recorded in 1 DMSO-d6 (Shown in Fig 4.9 and Fig 4.10). H-NMR of the LH ( 2b ) showed singlet at 9.17 ppm which was due to proton of the azomethine group (-CH=N-) most probably because of the effect of the ortho -hydroxyl group in the aromatic ring. A singlet at 8.23 ppm could be assigned for hydroxyl proton. The LH ( 2b ) displayed downfield shift of the –OH proton that was due to intramolecular (O-H...N) hydrogen bond [46]. 13 C-NMR spectra of ligand exhibited peaks at δ 135.95 and 135.87 assumably due to the phenolic (C-O) and imino (-CH=N) carbon atoms (due to Keto-imine tautomerism). The chemical shifts related to the aromatic carbons appeared at δ 123.60, 122.95, 122.40, 121.45 and 119.55.

Fig 4.9. 1H-NMR spectrumof LH ( 2b ).

Chapter IV

Fig 4.10. 13 C-NMR spectrum of LH ( 2b ).

4.3.4. Electronic absorption spectral and magnetic moment studies The UV-Visible spectra of the ligand and the metal complexes (shown in Fig 4.11) were recorded at room temperature using methanol as solvent. The electronic spectrum of LH ( 2b ) showed three absorption bands at 334, 248 and 217 nm due to n→π*, π→π * and transitions involved with the imidazolium moiety, respectively [47, 48]. The Mn(II) complex ( 3b ) exhibited three bands at 318, 254 and 210 nm. The ligand band at 334 nm showed a hypsochromic shift probably for coordination with Mn 2+ (d 5) ion. The electronic spectra of the Co(II) complex ( 3b ) exhibited three bands at 334, 249 and 210 nm and a shoulder around 390 nm. The bands were assigned to

Chapter IV

4 4 4 4 4 4 A2→ T1(P), A2→ T1(F) and A2→ T2 transitions, respectively. The experimental magnetic moment values were 5.79 and 3.87 B.M. for 3b and 4b respectively . So, The UV-Vis spectra along with the magnetic moment values of Mn(II) complex and Co(II) complex proposed tetrahedral geometry for both the cases [49]. UV-visible spectra of Cu(II) complex ( 5b ) showed d →π* metal-ligand charge transfer transition 2 2 (MLCT) in the region 397 nm had been assigned to the combination of B1g → Eg and 2 2 B1g → B2g transitions in a distorted square planar environment [50, 51]. The observed magnetic moment for Cu(II) complex ( 5b ) was 1.81 B.M. consistent with the presence of an unpaired electron.

Fig 4.11. UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): (A) LH ( 2b ); (B) Mn(II) complex ( 3b ); (C) Co(II) complex ( 4b ) and (D) Cu(II) complex ( 5b ).

4.3.6. Antibacterial activities The newly synthesized metal complexes ( 3b , 4b and 5b ) along with the ligand (2b ) were screened against the gram negative bacteria Escherichia Coli and gram positive bacteria. Bacillus subtilis. No clear inhibition zone surrounding the well were formed against the ligand and its Cu(II) complex. (Minimum inhibition concentration

Chapter IV against Escherichia coli was shown in Fig 4.12), whereas Mn(II) and Co(II) complex showed antibacterial activities with well diameter in the range of 3.5-1.3 mm, respectively at the concentrations of 125, 250, 750 and 1000 µg/mL against the bacteria studied. The result was given in Table 4.1 and Table 4.2.

Table 4.1. Antibacterial assay data of Schiff base ( 2b ) and its metal complexes ( 3b , 4b and 5b ) against Escherichia Coli . Compound 250 µg/mL 125 µg/mL 62.5 µg/mL 31.25 µg/mL

LH (2b) - - - -

Mn(II) complex (3b) 1.5mm 1.3 mm - -

Co(II) complex (4b) 2.5 mm 2.3 mm 2.2 mm 2.0 mm

Cu(II) complex (5b) - - - -

Table 4.2. Antibacterial assay data of Schiff base ( 2b ) and its metal complexes ( 3b , 4b and 5b ) against Bacillus subtilis . Compound 250 µg/mL 125 µg/mL 62.5 µg/mL 31.25 µg/mL

LH (2b) - - - -

Mn(II) complex (3b) 2.6 mm 2.3 mm 1.8 mm -

Co(II) complex (4b) 3.5 mm 3.2 mm 3.0 mm 2.8 mm

Cu(II) complex (5b) - - - -

Chapter IV

Fig 4.12 . Inhibition zones for anti-bacterial activities: A, for LH ( 2b ); B, for Mn(II) complex ( 3b ); C, for Co(II) complex ( 4b ); D, for Cu(II) complex ( 5b ) against Escherichia Coli .

4. 4. Conclusion In this study, synthesis, characterization and biological activities of the synthesized ionic liquid supported Schiff base and its metal complexes were reported. The complexes were formed in 1:2 (metal: ligand) ratio as confirmed by the spectral analysis. The results of different analytical and spectroscopic data revealed that the complexes had different coordination geometries. The Schiff base ligand played as a bidentate ligand and coordinated to metal ions through phenolic oxygen and the azomethine nitrogen. Again the synthesized ligand and the Cu(II) complex showed no antibacterial activities where as the Mn(II) and Co(II) complexes exhibited minimum activity against the two commonly known bacteria, viz. , Bacillus subtilis and Escherichia coli.

Chapter IV

References [1] J.P. Hallett, T. Welton, Chem. Rev., 111 (2011) 3508. [2] J.S. Wilkes, Green Chem., 4 (2002) 73. [3] A.J. Carmichael, M.J. Earle, J.D. Holbrey, P.B. McCormac, K R. Seddon, Org. Lett., 1(1999) 997. [4] N.V. Plechkova, K.R. Seddon, Chem. Soc. Rev., 37 (2008) 123. [5] T. Welton, Chem. Rev., 99 (1999) 2071. [6] K.R. Seddon, J. Chem. Technol. Biotechnol., 68 (1997) 351. [7] P. Wasserscheid, W. Keim, Angew. Chem., Int. Ed., 39 (2000) 3772. [8] R. Sheldon, Chem. Commun., (2001) 2399. [9] M.G. Freire, L.M.N.B.F. Santos, A.M. Fernandes, J.A.P. Coutinho, I.M. Marrucho, Fluid Phase Equilib., 261 (2007) 449. [10] H. Xie, S. Li, S. Zhang, Green Chem., 7 (2005) 606. [11] R.P. Swatloski, S.K. Spear, J.D. Holbrey, R.D. Rogers, J. Am. Chem. Soc., 124 (2002) 4974. [12] A. Biswas, R.L. Shogren, D.G. Stevenson, J.L. Willett, P.K. Bhowmik, Carbohydr. Polym., 66 (2006) 546. [13] M. Zavrel, D. Bross, M. Funke, J. Büchs, A.C. Spiess, Bioresour. Technol., 100 (2009) 2580. [14] S.S.Y. Tan, D.R. MacFarlane, J. Upfal, L.A. Edye, W.O.S. Doherty, A.F. Patti, J.M. Pringle, J.L. Scott, Green Chem., 11 (2009) 339. [15] C. Azubuike, H. Rodríguez, A. Okhamafe, R. Rogers, Cellulose., 19 (2012) 425. [16] J. Gao, Z.-G. Luo, F.-X. Luo, Carbohydr. Polym., 89 (2012) 1215. [17] M.E. Zakrzewska, E. Bogel-Lukasik, R. Bogel-Lukasik, Energy Fuels., 24 (2010) 737. [18] J.H. Davis, Jr., Chem. Lett., 33 (2004) 1072. [19] J. Fraga-Dubreuil, J.P. Bazureau, Tetrahedron Lett., 42 (2001) 6097. [20] W. Miao, T.H. Chan, Org. Lett., 5 (2003) 5003. [21] F. Yi, Y. Peng, G. Song, Tetrahedron Lett., 46 (2005) 3931. [22] E.D. Bates, R.D. Mayton, I. Ntai. J.H. Davis, J. Am. Chem. Soc., 124 (2002) 926.

Chapter IV

[23] A.C. Cole, J.L. Jensen, I. Ntai, K.L.T. Tran, J. Am. Chem. Soc., 124 (2002) 5962. [24] J. Li, Y. Peng, G. Song, Catal. Lett., 102 (2005) 159. [25] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.P. Cheng, Angew. Chem., Int. Ed., 45 (2006) 3093. [26] S. Chandra, K. Gupta, Trans. Met. Chem., 27 (2002) 196. [27] A.J. Atkins, D. Black, A.J. Blake, A. Marin-Bocerra, S. Parsons, L. Ruiz- Ramirez, M. Schröder, Chem. Commun., (1996) 457. [28] B. Rihter, S. Srittari, S. Hunter, J. Masnovi, J. Am. Chem. Soc., 115 (1993) 3918. [29] G. Occhipinti, V.R. Jensen, H.R. Bjrsvik, J. Org. Chem., 72 (2007) 3561. [30] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 235. [31] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 1384. [32] C.M. Liu, R.G. Xiong, X.Z. You, Y.J. Liu, K.K. Cheung, Polyhedron., 15 (1996) 4565. [33] S.S. Djebbar, B.O. Benali, J.P. Deloume, Transition Met. Chem., 23 (1998) 44. [34] Y.J. Hamada, IEEE Trans. Electron Devices., 44 (1997) 1208. [35] R. Ramesh, M. Sivagamasundari, Synth. React. Inorg. Met. Org. Chem., 33 (2003) 899. [36] S.K. Bharti, G. Nath, R. Tilak, S.K. Singh, Eur. J. Med. Chem., 45 (2010) 651. [37] K. Cheng, Q.Z. Zheng, Y. Qian, L. Shi, J. Zhao, H L. Zhu, Bioorg. Med. Chem., 17 (2009) 7861. [38] G. Song, Y. Cai, Y. Peng, J. Comb. Chem., 7 (2005) 561. [39] Y. Peng, Y. Cai, G. Song, J. Chen, Synlett., (2005) 2147. [40] Clinical and Laboratory Standards Institute (NCCLS) Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, 9th ed. M2-A9, Wayne, PA, (2006). [41] Clinical and Laboratory Standards Institute (NCCLS) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard, 7th ed., M7-A7, Wayne, PA, (2006). [42] M. Yıldız, Z. Kılıc, T. Hökelek, J. Mol. Struct., 1 (1998) 441.

Chapter IV

[43] G.-Y. Yeap, S.-T. Ha, N. Ishizawa, K. Suda, P.-L. Boey, W.A.K. Mahmood, J. Mol.Struct., 658 (2003) 87. [44] G.A. Kohawole, K.S. Patel, J. Chem. Soc., Dalton Trans., 6 (1981) 1241. [45] M.A. Mahmoud, S.A. Zaitone, A.M. Ammar. S.A. Sallam, J. Mol Struct., 1180 (2006) 60. [46] B. Li, Y.-Q. Li, W.-J. Zheng, M.-Y. Zhou, Arkivoc., 11 (2009) 165. [47] R.M. Silverstein, ‘Spectrometric Identification of Organic Compounds’, 7 th ed., John Wiley & Sons, (2005). [48] F. Peral, E. Gallego, J. Mol. Struc., 415 (1997) 187. [49] A.P. Lever, ‘Inorganic Electronic Spectroscopy’, 2 nd ed. Elsevier, New York, (1984). [50] C. Natarajan, P. Tharmaraj, R. Murugesan, J. Coord.Chem., 26 (1992) 205. [51] S. Dehghanpour, N. Bouslimani, R. Welter, F. Mojahed., Polyhedron., 26 (2007) 154.

CHAPTER V

Synthesis, structural characterization and exploration of antibacterial activities of Co(II), Ni(II) and Cu(II) complexes derived from an ionic liquid-supported Schiff base: 1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethylimidazolium tetrafluoroborate

5.1. Introduction Ionic liquids (ILs) may be defined as “ionic materials”, with low melting points (below 100 °C) generally composed of inorganic or organic anions paired with large, usually asymmetric organic cations. ILs pose a plethora of unique physicochemical and solvation characteristics that can be tuned for specific applications and often producing interesting results when employed instead of traditional molecular solvents [1, 2]. In addition, most ILs show negligible vapor pressure 3 as well as high thermal stability [4-6]. Due to these attractive features they are termed as neoteric solvents or green solvents. In recent years, ILs were extensively studied for their wide electrochemical window, high ionic conductivity [7] and a broad temperature range of the liquid state. Moreover, the physical properties of ILs including density, melting point, polarity, Lewis acidity, viscosity and enthalpy of vaporization can all be tuned by changing their cation and anion pairing [8]. IL-based solvent system typically exhibits enhanced reaction kinetics resulting in the efficient use of time and energy [1]. Due to these properties, ILs are treated as a new generation of solvents for catalysis, ecofriendly reaction media for organic synthesis and a successful replacement for conventional media in chemical processes [1,9]. Recently, many researchers have focused on the synthesis of new ionic liquids called functionalized ionic liquids (FILs) with different functional groups in the cationic moiety [10-15]. Such functionalization of the cation can easily be done in a single reaction step and thus both the cationic and anionic moieties of the FILs can be altered as required for specific applications like increased catalytic stability and reduced catalyst leaching etc [16,17]. Of note Schiff base being a salient class of multidentate ligand has played a key role in coordination chemistry. They exhibit varied denticities, chelating

Chapter V capability [18-20], functionalities [21] and diverse range of biological, pharmacological and antitumor activities. Schiff-bases containing hetero-atom such as N, O, and S are drawn special interest for their varied ways of coordination with different transition metal ions and having unusual configurations [22-24]. The present chapter describes the syntheses and physico-chemical characterizations of an IL- supported Schiff base, 1-{2-(2-hydroxy-5-nitrobenzylideneamino) ethyl}-3- ethylimidazolium tetrafluoroborate and its Co(II), Ni(II) and Cu(II) complexes. The ligand and its metal complexes were screened for their in vitro antibacterial activities against gram negative bacteria Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Enterobacter aerogenes and gram positive bacteria Staphylococcus aureus and Bacillus cereus. The complexes and the ligand were found most effective against the tested gram negative/positive bacteria. 5.2. Experimental Section 5.2.1. Materials and Methods Analytical grade chemicals were used for synthesis without further purification. 1-ethyl imidazole, 2-bromoethylamine hydrobromide, 5-nitro-2- hydroxybenzaldehyde and NaBF 4 (sodium tetrafluoroborate) were purchased from Sigma Aldrich, Germany. Metal acetates and other reagents were used as obtained from SD Fine Chemicals, India. CH 3OH, petroleum ether, CHCl 3, DMF and DMSO were used after purification by standard methods described in the literature. The FIL,

1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2-aeeim]BF 4 (1c ) was synthesized by following a literature procedure [25]. The synthesis and structural characterization of the [2-aeeim]BF 4 (1c ) have been earlier described in chapter II. FT-IR spectra were recorded by KBr pellets on a Perkin-Elmer Spectrum FT- IR spectrometer (RX-1). 1H-NMR spectra were recorded on a FT-NMR (Bruker

Avance-II 400 MHz) spectrometer by using D 2O and DMSO-d6 as solvents. Powder X-ray diffraction (XRD) data were obtained on INEL XRD Model Equinox 1000 using Cu K α radiation (2 θ= 0-90˚). Elemental microanalysis (CHN analysis) was performed on Perkin–Elmer (Model 240C) analyzer. Metal content was obtained from AAS (Varian, SpectrAA 50B) by using standard metal solutions procured from Sigma-Aldrich, Germany. Mass spectra were obtained on a JMS-T100LC spectrometer. The purity of the synthesized products was confirmed by thin layer

Chapter V chromatography (TLC) Merck 60 F254 silica gel plates (layer thickness 0.25 mm) and the spots were visualized using UV-light. The UV-Visible spectra were obtained from

JascoV-530 double beam Spectrophotometer using CH 3OH as solvent. Specific conductance was measured at (298.15 ± 0.01) K with a Systronic conductivity TDS- 308 metre. Magnetic susceptibility was measured with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1) at ambient temperature. The melting point of synthesized compounds was determined by open capillary method. Antibacterial activity ( in vitro ) of the synthesized ligand and complexes were evaluated by well diffusion method against six bacterial strains (Two gram positive and four gram negative). The bacterial strains were obtained from MTCC, Chandigarh, India. 5.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2c) Following literature procedure [26] 5-nitro-2-hydroxybenzaldehyde (1.67 g,

10 mmol) and [2-aeeim]BF 4 (2.27 g, 10 mmol) were taken in round bottomed flask and dissolved in methanol. The reaction mixture was stirred at 25 ºC for 4 h. After completion of reaction, the product diluted using ethanol. The precipitate was filtered, washed with cold EtOH and dried properly to collect the expected ligand as a yellowish brown solid. 2.85 g (yield, 75 %). M. p. 95-97 ºC. Anal. Calc. for

C14 H17 N4O3BF 4 (376): C, 44.71; H, 4.56; N, 14.90. Found: C, 44.64; H, 4.49; N, 14.83 %. FT-IR (KBr, cm -1) 3448 (O-H), 3071, 1664 (C=N), 1343 (N-O), 1293 (C- 1 O), 1095 (B-F). H NMR: (400 MHz, DMSO-d6): δ 3.36 (q, 2H, N-CH2), 3.60 (s, 3H,

CH3), 3.92 (t, 2H, N-CH2), 4.60 (t, 2H, N-CH2), 7.44 (s, 1H, NC H), 7.52 (s, 1H, NC H), 7.53 (s, 1H, N=C H), 7.61-7.59 (m, 3H, Ar-H), 8.65 (s, 1H, N( H)CN), 8.88 (s, 13 1H, O H). C NMR: (400 MHz, DMSO-d6): δ 159.76, 138.43, 134.08, 130.47, 130.31, 123.89, 119.80, 118.65, 110.65, 39.86, 39.65, 39.24, 39.03 and 38.82. UV-Vis + (Methanol, λmax): 206, 234, 306 nm; ESI-MS (CH 3OH, m/z): 289 ([M-BF 4] , M= + [C14 H17 N4O3] ). 5.2.3. Synthesis of the metal complexes (3c, 4c and 5c) To an ethanolic solution of ligand, LH ( 2c ) (0.376 g, 1 mmol) in round bottomed flask, Metal acetate salt Co(II), Ni(II) and Cu(II)), viz. , (0.5 mmol) dissolved in ethanol was added and the reaction mixture was refluxed for 12 h until the starting materials were completely consumed as monitored by TLC. On

Chapter V completion of the reaction, solvents were evaporated and the reaction mixture was cooled to room temperature. The precipitate was collected by filtration, washed successively with cold ethanol (10 mL × 3). Finally it was dried in vacuum desiccators to obtain the solid product. The complexes were soluble in N,N- dimethylformamide, dimethylsulphoxide, acetonitrile, methanol and water. The reactions are given in Scheme 5.1.

Scheme 5.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy-5- nitrobenzylideneamino)ethyl}-3-ethylimidazolium tetrafluoroborate ( 2c ), and its M(II) complexes ( 3c, 4c and 5c ) from ( 2c ).

5.2.2.1. Co(II) complex (3c): Brown solid; 0.54 g (yield, 67 %), decomposes o at ~ 293 C. Anal. Calc. for C28 H36 CoB 2F8N8O8 (809): 41.56; H, 3.99; N, 13.85, Co, 7.28. Found: C, 41.36; H, 3.71; N, 13.55, Co, 7.12 %. FT-IR (KBr, cm -1): 3386 (O- H), 1648 (C=N), 1332 (N-O), 1177 (C-O), 1106 (B-F), 651 (M-O), 510 (M-N). UV- + Vis (Methanol, λmax/nm): 227, 246, 358. ESI-MS (CH 3OH, m/z): 635 ([M-2BF 4] , + M= [(C 28 H32 CoN 8O6] ). 5.2.2.2. Ni(II) complex (4c): Light green solid; 0.56 g (yield, 69 %), o decomposes at ~ 291 C. Anal. Calc. for C28 H36 NiB 2F8N8O8 (809): C, 41.57; H, 3.99; N, 13.85; Ni, 7.26. Found: C, 41.22; H, 3.63; N, 13.46, Ni, 7.11 %. FT-IR (KBr, cm - 1): 3396 (O-H), 1637 (C=N), 1330 (N-O), 1172 (C-O), 1102 (B-F), 646 (M-O),

526(M-N). UV-Vis (Methanol, λmax/nm): 220, 340, 400. ESI-MS (CH 3OH, m/z): + + 634 ([M-2BF 4] , M= [(C 28 H32 NiN 8O6] ).

Chapter V

5.2.2.3. Cu(II) complex (5c): Dark green solid; 0.57 g (yield, 70 %), o decomposes at ~ 295 C. Anal. Calc. for C28 H36 CuB 2F8N8O8 (813.76): C, 41.33; H, 3.96; N, 13.77; Cu, 7.81. Found: C, 41.12; H, 3.61; N, 13.46, Cu, 7.61 %. FT-IR (KBr, cm -1): 3429 (O-H), 1656 (C=N), 1334 (N-O), 1175 (C-O), 1103 (B-F), 633 (M-

O), 471 (M-N). UV-Vis (Methanol, λmax/nm): 226, 244, 354. ESI-MS (CH 3OH, + + m/z): 639 ([M-2BF 4] , M= [(C 28 H32 CuN 8O6] ). 5.4.4. Antibacterial assay The synthesized ligand (2c ) and complexes ( 3c, 4c and 5c) were screened against the gram negative bacteria ( E. coli, P. aeruginosa, P. vulgaris and E. aerogenes ) and gram positive bacteria ( S. aureus and B. cereus ) strains. The tests were performed using agar disc diffusion method [27]. The nutrient agar (Hi-Media Laboratories Limited, Mumbai, India) was put in an autoclave at 121 ˚C and 1 atm for 15-20 minutes. The sterile nutrient medium was kept at 45-50 ˚C and then 100 µL of bacterial suspension containing 10 8 colony-forming units (CFU)/mL was mixed with sterile liquid nutrient agar and poured into the sterile Petri dishes. All the stock solutions were made by dissolving the compounds in dimethyl sulphoxide (DMSO). The concentrations of the tested compounds were 10, 20, 30, 40 and 50 µg/mL. The tested microorganisms were grown on nutrient agar medium in Petri dishes. The samples were soaked in a filter paper disk of 1 mm thickness and 5 mm diameter. The discs were kept on Petri plates and incubated for 24 hours at 37 oC. The diameter of the inhibition zone (including disc diameter of 5 mm) was measured. Each experiment was carried out three times to minimize the error and the mean values were accepted. 5.3. Results and Discussion All the isolated compounds were stable at room temperature to be characterized by different analytical and spectroscopic methods. 5.3.1. FT-IR spectral studies The assignments of the IR bands of the synthesized Co(II), Ni(II) and Cu(II) complexes had been made by comparing with the bands of ligand (LH) to determine the coordination sites involved in chelation. FT-IR spectra of LH ( 2c ) showed a strong broad band at 3448-3071 cm -1; which was due to the hydrogen bonded phenolic group (-OH) with H–C(=N) group in the ligand (OH…N=C) [28, 29]. The broad band appeared at 3386-3429 cm -1 for the metal complexes ( 3c , 4c and 5c ) suggested the

Chapter V

presence of the solvated water molecules (probably for the presence of –NO 2 group in the ligand and intrinsic property of the anion tetrafluoroborate) [30-32]. The band corresponding to the azomethine group (-C=N) of the ligand was found at 1664 cm -1. This band gets shifted in the range 1637-1656 cm -1 because of coordination of N atom of azomethine linkage to the Co +2 , Ni +2 and Cu +2 ions respectively [33]. The band for phenolic C-O of free ligand was observed at 1293 cm-1 which moved to lower wave number 1172-1177 cm -1 for the complexes ( 3c, 4c and 5c ) upon complexation. This fact established the bonding of ligand ( 2c ) to the metal atoms through the N atom of azomethine and O atom of phenolic group [34]. The bands appeared in the region of 1102-1107 cm -1 for the metal complexes were assigned for B-F stretching frequency. FT-IR spectra of the LH ( 2c ) and its complexes showed strong bands at 1330-1343 -1 cm which were assigned for the NO 2 group [35]. The spectra of the metal complexes exhibited bands at 633-651 and 471-526 cm -1 were attributed to M-O and M-N stretching vibrations, respectively [36]. FT-IR spectra of the Schiff base and its metal complexes are given in Figs 5.1-5.4.

Fig 5.1. FT -IR spectrum of LH ( 2c ).

Chapter V

Fig 5.2. FT -IR spectrum of Co(II) complex ( 3c ).

Fig 5.3. FT -IR spectrum of Ni(II) complex ( 4c ).

Chapter V

Fig 5.4. FT -IR spectrum of Cu(II) complex ( 5c ).

5.3.2. Mass spectral studies To get information regarding the structure of the synthesized compounds at the molecular level, electrospray ionization (ESI) mass spectrometry was performed using methanol as solvent. Mass-spectra of the LH (2c ) had a molecular ion peaks at + + m/z 289, that corresponds to [M- BF 4] , [M= C 14 H17 N4O2] . The metal complexes ( 3c, + 4c and 5c ) exhibited molecular ion peaks ( m/z ) at 635 (M= [C 28 H32 CoN 8O6] ), at 634 + + (M= [C 28 H32 CuN 8O6] ) and at 639 (M= [C 28 H32 CuN 8O6] ) which confirmed their stoichiometry as Co(L) 2, Ni(L) 2 and Cu(L) 2 respectively. The mass spectra of the ligand and complexes were in good agreement with the respective structures as revealed by the elemental and other spectral analyses. The ESI-MS spectra of the ligand and complexes are shown in Figs 5.5-5.8.

Chapter V

Fig 5.5 . ESI-MS spectrum of LH ( 2c ).

Fig 5.6 . ESI-MS spectrum of Co(II) complex ( 3c ).

Chapter V

Fig 5.7. ESI-MS spectrum of Ni(II) complex (4c ).

Fig 5.8 . ESI-MS spectrum of Cu(II) complex ( 5c ).

Chapter V

5.3.3. 1H and 13 C-NMR spectral studies 1 13 H-NMR and C-NMR spectra of Schiff base were recorded in DMSO-d6 (Shown in Fig 5.9 and Fig 5.10). 1H-NMR spectra of the ligand showed singlet at 7.60 ppm which was assignable to proton of the azomethine linkage (-CH=N-) might be because of the effect of the ortho -hydroxyl group in the aromatic ring. A singlet at 8.88 ppm was assigned to hydroxyl proton (-OH). The downfield shift of the phenolic (–OH) proton was observed due to intramolecular (O-H...N) hydrogen bonding in the ligand [37]. 13 C-NMR spectra of ligand exhibited peaks at δ 159.76 and 138.43 which were detected for the phenolic (C-O) and imino (-CH=N) carbon atoms (due to Keto- imine tautomerism). The aromatic carbons showed pecks at δ 134.08, 130.47, 130.31, 123.89, 119.80 and 118.65.

Fig 5.9. 1H-NMR spectrumof LH ( 2c ).

Fig. 5.10. 13 C-NMR spectrum of LH (2c ).

5.3.4. Powder X-ray diffraction analysis The PXRD analysis of the synthesized compounds was carried out to find whether the particle nature of the samples was amorphous or crystalline. The PXRD spectrum of ligand (LH) exhibited sharp peaks because of their crystalline nature although the spectra of the two complexes didn’t show such peaks for their amorphous nature (Shown in Figs 5.11-5.14). The crystalline sizes were calculated using Debye Scherer’s equation: D= 0.9 λ/βcos θ, where constant 0.9 is the shape factor, λ is the X-ray wavelength (1.5406 Å), β is the full width at half maximum (FWHM) and θ is the Bragg diffraction angle. The experimental average grain sizes of LH and its metal complexes were found to be 31.71 nm ( 2c ), 7.76 nm ( 3c ), 3.26 nm (4c ) and 4.52 nm ( 5c ).

Chapter V

Fig 5.11. PXRD patterns of LH ( 2c ).

Fig 5.12. PXRD patterns of Co(II) complex( 3c ).

Chapter V

Fig 5.13. PXRD patterns of Ni(II) complex ( 4c ).

Fig 5.14. PXRD patterns of Cu(II) complex ( 5c ).

Chapter V

5.3.5. Molar conductance measurements

The molar conductance ( Λm) of the complexes ( 3c , 4c and 5c ) was determined by applying the relation Λm = 1000× κ/c, where κ and c stands for the specific conductance and molar concentration of metal complexes respectively. The complexes (1 × 10 −3 M) were dissolved in DMF and their specific conductance was measured at (298.15 ±0.01) K. The molar conductance data was observed as 123, 128 and 131 S cm -1mol -1 for the metal complexes 3c, 4c and 5c respectively indicating their 1:2 electrolytic natures. 5.3.6. Electronic absorption spectral and magnetic moment studies The UV-Visible spectra of the Schiff base and its metal complexes (as depicted in Fig 5.15.) were recorded at room temperature using methanol as solvent. The LH ( 2c ) exhibited three absorption bands at 306, 234 and 206 nm due to n →π*, π→π * and transitions involved with the imidazolium moiety, respectively [38, 39]. For the complexes, the bands that appeared below 350 nm were ligand centred transitions (n →π* and π→π *). The Co(II) complex ( 3c ) displayed a band at 354 nm 2 1 1 2 which could be attributed to the combination of B1g → A1g and B1g → Eg transitions and supporting square planar geometry [40, 41]. The complex ( 3c ) showed magnetic moment of 2.30 B.M. due to one unpaired electron. The Ni(II) complex ( 4c ) was 1 1 diamagnetic and the band appeared at around 400 nm due to A1g → B1g transition is consistent with low spin square planar environment [42]. UV-visible spectra of Cu(II) complex ( 5c ) exhibited d →π* metal-ligand charge transfer transition (MLCT) at the 2 2 2 2 region 358 nm had been assigned to the combination of B1g → Eg and B1g → B2g transitions in a distorted square planar geometry [43, 44]. The experimental magnetic moment value for 5c was 1.84 B.M. consistent with the presence of an unpaired electron [45].

100

Chapter V

Fig 5.15. . UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): (A) LH ( 2c ); (B) Co(II) complex (3c ); (C) Ni(II) complex (4c ) and (D) Cu(II) complex (5c ).

5.3.6. Antibacterial activities Antibacterial study of LH ( 2c ) and its complexes (3c , 4c and 5c ) was carried out in vitro against the gram negative/positive bacterial strains and the results were displayed in Table 5.1, Table 5.2 and also in Fig 5.16. Minimum inhibitory concentration (MIC) was measured by Broth Micro dilution susceptibility method. No inhibition zone was found for the solvent control (DMSO) for each bacterial suspension. A serial dilution of sample extracts was made in nutrient broth medium. Then 1 mL of standard ( 0.5 Mc Farland ) bacterial suspension was inoculated into each of these tubes. A similar nutrient broth tube without sample extract was also inoculated and used as control. The samples under investigation have shown promising results against the tested bacterial strains. The LH ( 2c ) was most effective against S. aureus only. The Co(II) complex ( 3c ) showed most effectiveness against S. aureus , E. aerogenes . The Ni(II) complex ( 4c ) showed higher acitivity against E. aerogenes . Although in other cases it showed moderate activity. It was found that

101

Chapter V

Table 5.1. Antibacterial activity data of Schiff base ( 2c ) and its metal complexes ( 3c , 4c and 5c ) against E. Coli, S. aureus and B.cereus . Concentration (µg/mL) Specimen E. coli S. aureus B.cereus 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 LH (2c) - 6 7 8 12 7 9 10 10 12 - - 6 8 12 Co(II) - - 6 7 8 6 7 7 9 10 - 6 6 8 10 complex (3c) Ni(II) 6 7 8 9 9 - - 7 8 10 - - 6 8 10 complex (4c) Cu(II) 8 9 14 15 18 6 8 10 17 17 - - - - 7 complex (5c)

Table 5.2. Antibacterial activity data of Schiff base ( 2c ) and its metal complexes ( 3c , 4c and 5c ) against P. aeruginosa, P. vulgaris and E. aerogenes . Concentration (µg/mL) Specimen P. aeruginosa P. vulgaris E. aerogenes 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 LH (2c) - 6 9 15 16 - 6 9 10 14 - 6 8 10 13 Co(II) - 7 9 10 13 - - - 6 7 8 10 13 15 17 complex (3c) Ni(II) - - 6 7 9 - - 6 7 8 8 10 12 12 16 complex (4c) Cu(II) - 6 12 12 14 - 7 7 8 16 - - 6 7 10 complex (5c)

102

Chapter V

Fig 5.16 . Inhibition zones for the LH ( 2c ), Co(II) complex ( 3c ), Ni(II) complex ( 4c ) and Cu(II) complex ( 5c ).

Cu(II) complex ( 5c ) was most effective against the tested bacteria. The observation suggested that the chelation could facilitate the capability of the complexes to penetrate bacterial cell membrane [46]. Such a chelation could enhance the lipophilic property of the corresponding metal ions that favours permeation towards the lipid layer of cell membrane. The activity of both the complexes and ligand enhanced as the concentration was increased which were due to the growth of degree of inhibition. 5. 4. Conclusion Herein this chapter, new Co(II), Ni(II) and Cu(II) complexes of an ionic liquid-based Schiff base, 1-{2-(2-hydroxy-5-nitrobenzylideneamino)ethyl}-3- ethylimidazolium tetrafluoroborate were synthesized and characterized by different spectral and analytical techniques. The Schiff base ligand played as a potential bidentate ligand coordinating through the N-atom of azomethine and O-atom of phenolic group to the metal ions and thus formed 1:2 (M:L) complexes. Spectral and magnetic susceptibility data revealed that the ligand was arranged in square planner

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Chapter V geometry around the central metal ions. The antibacterial study of the synthesized compounds was performed and metal complexes have exhibited promising activity against the tested bacteria. References [1] T. Welton, Chem. Rev., 99 (1999) 2071. [2] C. Chiappe, D. Pieraccini, J. Org. Chem., 69 (2004) 6059. [3] M.J. Earle, J.M.S.S. Esperanc, M.A. Gilea, J.N.C. Lopes, L.P.N. Rebelo, J. Magee, K.R. Seddon, J.A. Widegren, Nature., 439 (2006) 831. [4] R.D. Rogers, K.R. Seddon, Science., 302 (2003) 792. [5] R. Sheldon, Green Chem., 7 (2005) 267. [6] P. Wasserscheid, W. Keim, Angew. Chem. Int. Ed., 39, (2000) 3772. [7] H. Sakaebe, H. Matsumoto, Electrochem. Commun., 5 (2003) 594. [8] M.G. Freire, L.M.N.B.F. Santos, A.M. Fernandes, J.A.P. Coutinho, I.M. Marrucho, Fluid Phase Equilibr., 261, (2007) 449. [9] R. Sheldon, Chem. Commun., 23 (2001) 2399. [10] F. Yi, Y. Peng, G. Song, Tetrahedron Lett., 46 (2005) 3931. [11] E.D. Bates, R.D. Mayton, I. Ntai, J. Am. Chem. Soc., 124 (2002) 926. [12] A.C. Cole, J.L. Jensen, I. Ntai, J. Am. Chem. Soc., 124 (2002) 5962. [13] J. Li , Y. Peng, G. Song, Catal. Lett., 102 (2005) 159. [14] J.H. Davis Jr., K.J.T. Forrester, Tetrahedron Lett., 49 (1998) 8955. [15] J.J. Jodry, K. Mikami, Tetrahedron Lett., 45 (2004) 4429. [16] Z. Fei, T.J. Geldbach, D. Zhao, P.J. Dyson, J. Eur. Chem., 12 (2006) 2122. [17] S.G. Lee, Chem. Commun., 14 (2006) 1049. [18] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 235. [19] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 1384. [20] C.M. Liu, R.G. Xiong, X.Z. You, Y.J. Liu, K.K. Cheung, Polyhedron., 15 (1996) 4565. [21] A.J. Atkins, D. Black, A.J. Blake, A. Marin-Bocerra, S. Parsons, L. Ruiz- Ramirez, M. Schröder, Chem. Commun., (1996) 457. [22] A. Goku, M. Tumer, H. Demirelli, R.A. Wheatley, Inorg. Chim. Acta. 358 (2005) 1785.

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[23] A. Mohindru, J.M. Fisher, M. Rabinovitz, Nature., 303 (1983) 64. [24] P.R. Palet, B.T. Thaker, S. Zele , Indian. J. Chem. A., 38 (1999) 563. [25] G. Song, Y Cai, Y Peng, J. Comb. Chem., 7 (2005) 561. [26] B. Li, Y.Q. Li, J. Zheng, Arkivoc., IX (2010) 163. [27] I. Ahmed, A.J. Beg, J. Ethnopharmacol., 74 (2001) 113. [28] M. Yıldız, Z. Kılıc, T. Hökelek , J. Mol. Struct ., 441 (1998) 1. [29] G.-Y. Yeap, S.-T. Ha, N. Ishizawa, K. Suda, P.-L. Boey, W.A.K. Mahmood, J. Mol. Struct., 658 (2003) 87. [30] S.A. Abdel-Latif, H.B. Hassib, Y.M. Issa, Spectrochimica. Acta. Part.A., 67 (2007) 950. [31] J. Wang, Y. Pei, Y. Zhao, Z. Hu, Green Chem., 7 (2005) 196. [32] D. Han, K.H. Row, Molecules., 15 (2010) 2405. [33] G.A. Kolawole, K.S. Patel, J. Chem. Soc. Dalton Trans., 6 (1981) 1241. [34] M.A. Mahmoud, S.A. Zaitone, A.M. Ammar. S.A. Sallam, J. Mol Struct., 1108 (2006) 60. [35] N. Ulusoy, A. Gürsoy, G. Ötük, II Farmaco., 56 (2001) 947. [36] D.M. Adams, Metal-Ligand and Related Vibrations: A Critical Survey of the Infrared and Raman Spectra of Metallic and Organometallic Compounds, Edward Arnold (Publishers) Ltd London, England, 1967. [37] B. Li, Y.-Q. Li, W.-J. Zheng, M.-Y. Zhou, Arkivoc., 11 (2009) 165. [38] R.M. Silverstein, ‘Spectrometric Identification of Organic Compounds’, 7 th ed., John Wiley & Sons, (2005). [39] F. Peral, E. Gallego, J. Mol. Struc., 415 (1997) 187. [40] M. Shakir, O.S.M. Nasam, A.K. Mohamed, Polyhedron., 15 (1996) 1283 [41] L.S. Chem, S.C. Cummings, Inorg. Chem., 17 (1978) 2358. [42] A.A. Del Paggio, D.R. McMillin, Inorg. Chem., 22 (1983) 691. [43] C. Natarajan, P. Tharmaraj, R. Murugesan, J. Coord.Chem., 26 (1992) 205. [44] S. Dehghanpour, N. Bouslimani, R. Welter, Polyhedron., 26 (2007)154. [45] A.B.P. Lever, ‘Inorganic Electronic Spectroscopy’, 2 nd ed. Elsevier, Amsterdam, (1984). [46] B.G. Tweedy, Phytopathology., 55 (1964) 910.

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Physico-chemical characterization and biological studies of newly synthesized metal complexes of an Ionic liquid-supported Schiff base: 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3- ethylimidazolium tetrafluoroborate *

6.1. Introduction Ionic liquids (ILs) are organic salts that have low melting points below the boiling point of water and are stable in liquid state at 100 °C, even at room temperature. They can exhibit numerous desirable properties such as negligible vapor pressure [1], ability to dissolve various substrates; high electrical conductivity [2] and thermal stability [3-5]. ILs are considered as alternatives to volatile organic solvents (VOC) in various organic transformations. Due to low toxicity and biodegradability they have been termed as green solvents [6]. An unusual feature of ILs is the tenability of their physical and chemical properties by variation of cations and anions. Usually large organic cations and smaller anions are designed to carry on required functions [7]. Although most of the works on ILs highlight their use as reaction media in organic synthesis, these liquids are gradually drawing attention in the field of inorganic and material chemistry [8, 9]. The concept of functionalized ionic liquid (FILs), by introducing additional functional group as a part of cation or anion, has presently become a subject of interest [10-15]. There is huge possibility of chemical structure modifications through the incorporation of specific functionality. Such FILs are able to interact with a metal centre and contribute to an enhanced stability of metal salts [16]. Metal containing ILs are considered as promising new material that combine the feature of ILs with additional intrinsic magnetic, catalytic and spectroscopic properties depending on the incorporated metal ion [17]. Schiff bases, usually formed by the condensation of primary amine with an aldehyde are one of the most prevalent ligands in coordination chemistry [18]. Schiff- bases containing hetero-atoms such as nitrogen, oxygen and sulphur are of special interest due to their different ways of bonding with transition metal ions and unusual

*Published in J. Chem. Sci. 130 (2018 ) 1-9. 106

Chapter VI configuration [19]. They have been reported to exhibit a variety of biological actions due to the presence of azomethine linkage, which is responsible for different types of antibacterial, herbicidal and antifungal activities [20, 21]. Transition metal complexes of Schiff bases carrying nitrogen and other donor sites have a variety of applications including biological, medicinal analytical in addition to their vital role in organic synthesis and catalysis [22-26]. Hence, in this chapter, I have reported the synthesis of Co(II), Ni(II) and Cu(II) complexes of an ionic liquid supported Schiff base and their characterization using spectroscopic, analytical and magnetic data. Furthermore the applications of the Schiff base and its complexes as potential antibacterial agents have also been explored. 6.2. Experimental Section 6.2.1. Materials and Methods All the reagents were of analytical grade and used without further purification. 1-ethylimidazole, 2-bromoethylamine hydrobromide and sodium tetrafluoborate were procured from Sigma Aldrich, Germany. 5-bromo-2-hydroxybenzaldehyde, Co(II), Ni(II) and Cu(II) acetates and all other chemicals were used as received from SD Fine Chemicals, India. The solvents methanol, petroleum ether, chloroform, DMF and DMSO were used after purification by the standard methods describe in the literature. The amino functionalized ionic liquid, 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2-aeeim]BF 4 (1c ) was synthesized by following a literature procedure [27]. The synthesis and physicochemical characterization of the FIL has been illustrated earlier in chapter II. IR spectra were recorded in KBr pellets with a Perkin-Elmer Spectrum FT-IR spectrometer (RX-1) operating in the region 4000 to 400 cm -1. 1H-NMR was recorded at room temperature on a FT-NMR (Bruker Avance-II 400 MHz) spectrometer by using DMSO-d6 and D 2O as solvents. Chemical shifts are mentioned in ppm downfield of internal standard tetramethylsilane (TMS). Elemental microanalyses (C, H and N) were conducted by using Perkin–Elmer (Model 240C) analyzer. Metal content were determined with the aid of AAS (Varian, SpectrAA 50B) by using standard metal solutions from Sigma-Aldrich, Germany. Mass spectra were recorded on a JMS-T100LC spectrometer. The purity of the prepared compounds was confirmed by thin layer chromatography (TLC) on silica gel plates and the plates

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Chapter VI were visualized with UV-light and iodine as and when required. The UV-Visible spectra were recorded in methanol with a JascoV-530 double beam Spectrophotometer at ambient temperature. Specific conductance was measured at (298.15 ± 0.01) K with a Systronic conductivity TDS-308 metre. Magnetic susceptibilities were measured at room temperature with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1). The melting point of the ligand and its complexes were determined by open capillary method. Antibacterial activities (in vitro ) of the synthesized compounds were tested by disc diffusion method. All the bacteria strains were procured from MTCC, Chandigarh, and were cultured at the Department of Microbiology, Raiganj University, Raiganj, West Bengal, India. 6.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2d) The ionic liquid-supported Schiff base (LH) was synthesized by following a literature procedure [28]. A mixture of 5-bromo-2-hydroxybenzaldehyde (2.01 g, 10 mmol) and [2-aeeim]BF 4 (2.27 g, 10 mmol) in methanol was stirred at room temperature for 12 h. After completion of the reaction, as indicated by TLC, the reaction mixture was diluted with ethanol. The precipitate was filtered, washed with cold ethanol and dried to afford the expected ligand as light yellow solid. 3.03 g

(yield 75 %). M.p.: 98-100 ºC; Anal. Calc. for C 14 H17 N3OBBrF 4 (410): C, 41.01; H, 4.18; N, 10.25. Found: C, 40.91; H, 4.11; N, 10.21 %. FT-IR (KBr, cm -1): 3449 (O- 1 H), 1673 (C=N), 1276 (C-O), 1114 (B-F). H NMR: (400 MHz, DMSO-d6): δ 2.49 (s,

3H, CH 3), 3.82 (t, 1H, N-CH2), 3.99 (t, 1H, N-CH2), 4.52 (t, 1H, N-CH2), 6.91–6.85 (m, 3H, Ar-H), 7.33 (s, 1H, NCH), 7.42 (s, 1H, NCH), 8.50 (s, 1H, N=CH), 7.73 (s, 13 1H, N(H)CN), 9.10 (s, 1H, OH). C NMR (400 MHz, DMSO-d6): δ 137.31, 135.59, 123.76, 123.09, 122.41, 122.25, 119.63, 53.91, 48.52, 48.14, 44.99, 43.71, 41.15,

35.90. UV-Vis (Methanol) λmax/nm: 218, 250, 336. ESI-MS (CH 3OH, m/z): 322 + + ([M-H-BF 4] , M= [C 14 H17 N3OBr] ). 6.2.3. Synthesis of the metal complexes (3d, 4d and 5d) To a ethanolic solution (20 mL) of LH ( 2d ) (0.410 g, 1 mmol) in a round bottomed flask equipped with a condenser, metal acetate salt of Co(II), Ni(II) and Cu(II)), viz. , (0.5 mmol) dissolved in ethanol was added gradually. The reaction mixture was refluxed for 4 h until the starting materials were completely consumed as monitored by TLC. On completion of the reaction, solvents were evaporated and the

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Chapter VI reaction mixture was cooled to room temperature. The precipitate was collected by filtration, washed successively with cold ethanol (10 mL × 3). Finally it was dried in vacuum desiccators to obtain the solid product. The complexes are soluble in N, N- dimethylformamide, dimethylsulphoxide, acetonitrile, methanol and water. A schematic representation of the synthesis procedure is shown in Scheme 6.1.

Scheme 6.1. Synthesis of the ionic liquid supported Schiff base, 1-{2-[(2-hydroxy-5- bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate ( 2d ), and its metal complexes ( 3d, 4d and 5d ) from ( 2d ).

6.2.2.1. Co(II) complex (3d): Brown solid; 0.62 g (yield, 71 %) M. p.: 128- o 130 C; Anal. Calc. for C 28 H32 CoB 2Br 2F8N6O2 (877): C, 38.35; H, 3.68; N, 9.58; Co, 6.72. Found: C, 38.16; H, 3.53; N, 9.32, Co, 6.42 %. FT-IR (KBr, cm -1): 3442 (O-H), 1629 (C=N), 1316 (C-O), 1019 (B-F), 633 (M-O), 523 (M-N). UV-Vis (Methanol) + λmax/nm: 220, 338, 394. ESI-MS (CH 3OH, m/z): 701 [M-2BF 4] , M= + [C 28 H32 CoBr 2N6O2] ). 6.2.2.2. Ni(II) complex (4d): Light green solid; 0.60 g (yield, 69%). M. p. o 140-142 C; Anal. Calc. for C 28 H32 NiB 2Br 2F8N6O2 (876.7): C, 38.36; H, 3.68; N, 9.58; Ni, 6.69. Found: C, 38.11; H, 3.50; N, 9.37, Ni, 6.33 %. FT-IR (KBr, cm -1): 3437 (O-H), 1627 (C=N), 1314 (C-O), 1018 (B-F), 634 (M-O), 535 (M-N). UV-Vis

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+ (Methanol) λmax/nm: 219, 340, 400. ESI-MS (CH 3OH, m/z): 702 ([M+2H-2BF 4] , + M= [C 28 H32 NiBr 2N6O2] ). 6.2.2.3. Cu(II) complex ( 5d): Dark green solid; 0.64 g (yield, 73 %). M. p. o 147-149 C; Anal. Calc. for C 28 H32 CuB 2Br 2F8N6O2 (881.56): C, 38.15; H, 3.66; N, 9.53; Cu, 7.21. Found: C, 38.07; H, 3.49; N, 9.31, Cu, 6.99%. FT-IR (KBr, cm -1): 3448 (O-H), 1625 (C=N), 1317 (C-O), 1014 (B-F), 648 (M-O), 559 (M-N). UV-Vis + (Methanol) λmax/nm: 222, 342, 396. ESI-MS (CH 3OH, m/z): 705.74 [M-2BF 4] , M= + [C 28 H32 CuBr 2N6O2] . 6.4.4. Antibacterial assay Antibacterial activities of the synthesized compounds were tested in vitro against the four Gram negative bacteria ( E. coli, P. aeruginosa, P. vulgaris and E. aerogenes ) and two Gram positive bacteria ( S. aureus and B. cereus ) strains using agar disc diffusion method [29, 30] by NCCLS (National Committee for Clinical Laboratory Standards, 1997). The nutrient agar (Hi-Media Laboratories Limited, Mumbai, India) was autoclaved at 121 oC and 1 atm for 15-20 minutes. The sterile nutrient media was kept at 45-50˚C, after that 100 µL of bacterial suspension containing 10 8 colony-forming units (CFU)/mL were mixed with sterile liquid nutrient agar and poured into the sterile Petri dishes. Upon solidification of the media, filter disc (5 mm diameter) was individually soaked with different concentration (10, 20, 30, 40 and 50 µg/mL) of each sample solution and placed on the nutrient agar media plates. The different concentrations were made by diluting with DMSO. The plates were incubated for 24 hours at 37 oC. The diameter of the zone of inhibition (including disc diameter of 5 mm) was measured. Each experiment was performed three times to minimize the error and the mean values were accepted. 6.3. Results and Discussion All the isolated compounds were stable at room temperature to be characterized by different analytical and spectroscopic methods. 6.3.1. FT-IR spectral studies The assignments of the IR bands of the synthesized Co(II), Ni(II) and Cu(II) complexes have been made by comparing with the bands of ligand (LH) to determine the coordination sites involved in chelation. Only the distinct and characteristic peaks have been discussed. FT-IR spectra of the ligand exhibited a strong broad absorption

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Chapter VI band at 3450.61-3236 cm -1; this band was assigned to the hydrogen bonded -OH of the phenolic group with H–C(=N) group of the ligand (OH…N=C) [31, 32]. All the complexes showed broad diffuse band at 3437-3448 cm-1 that may be attributed to the presence of the solvated water or ethanol molecules. However, these bands appear stronger compare to that of the ligand due to the moisture content of the ligand subject to the intrinsic nature of the anion tetrafluoroborate [33-35]. The band for phenolic C- O of free ligand was observed at 1276 cm -1. Upon complexation, this band was shifted to higher wave number 1314-1317 cm -1 for all the complexes. This fact suggested the involvements of phenolic C-O in the coordination process [36]. This interpretation is further confirmed by the appearance of M-O band at 633-638 cm -1 in the spectra of the metal complexes. The intense band at 1673 cm -1 that corresponds to azomethine group (-C=N) in the free ligand was shifted to the lower frequencies in the range 1625-1629 cm -1 in case of the metal complexes, indicating the participation of azomethine group (-C=N) in the coordination sphere [37]. This was further emphasized by the appearance of a new weak to medium intensity absorption band in the region 523-559 cm -1 that could be attributed to M-N stretching vibration for the metal complexes [38]. The bands in the range of 1014-1114 cm -1 for the spectra of the ligand and metal complexes were assigned for B-F stretching frequency. IR spectra of the ligand, LH ( 2d ) and its metal complexes ( 3d, 4d and 5d) are given in Figs 6.1-6.4.

Fig 6.1. FT -IR spectrum of LH ( 2d ).

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Fig 6.2. FT -IR spectrum of Co(II) complex ( 3d ).

Fig 6.3. FT -IR spectrum of Ni(II) complex ( 4d ).

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Fig 6.4. FT -IR spectrum of Cu(II) complex ( 5d ).

6.3.2. Mass spectral studies To get information regarding the structure of the synthesized compounds at the molecular level, electrospray ionization (ESI) mass spectrometry was performed using methanol as solvent. The ligand (LH) exhibited a peak ( m/z ) at 322 which could + + be assigned to [M-H-BF 4] ion, [M= C 14 H17 N3OBr] [39]. The Co(II) complex ( 3d ) + displayed a peak ( m/z ) at 701.49 which was due to the [M-2BF 4] (M= + [C 28 H32 CoBr 2N6O2] ) ion. A peaks ( m/z ) at 701.62 in the ESI-MS spectrum of Ni(II) + + complex ( 4d ) was assigned for the [M+H-2BF 4] (M= [C 28 H32 NiBr 2N6O2] ) ion. The Cu(II) complex (5d ) exhibited a peak ( m/z ) at 705.74 which was attributed to [M- + + 2BF 4] (M= [C 28 H32 CuBr 2N6O2] ) ion [40]. The mass spectra of the ligand and complexes were in good agreement with the respective structures as revealed by the elemental and other spectral analyses. The ESI-MS spectra of the ligand and complexes are shown in Figs 6.5-6.8.

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Fig 6.5 . ESI-MS spectrum of LH ( 2d ).

Fig 6.6 . ESI-MS spectrum of Co(II) complex ( 3d ).

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Fig 6.7. ESI-MS spectrum of Ni(II) complex ( 4d ).

Fig. 6.8 . ESI-MS spectrum of Cu(II) complex ( 5d )

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6.3.3. 1H and 13 C-NMR spectral studies 1 13 H-NMR and C-NMR spectra of Schiff base were recorded in DMSO-d6 (Shown in Fig 6.9 and Fig 6.10). 1H-NMR of the ligand (LH) showed singlet at δ 8.50 ppm assignable to proton of the azomethine group (-CH=N-) presumably due to the effect of the ortho -hydroxyl group in the aromatic ring. A singlet at δ 9.10 ppm could tentatively be attributed to hydroxyl proton. The LH ( 2d ) displayed downfield shift of the –OH proton was due to intramolecular (O-H...N) hydrogen bond [41]. 13 C-NMR spectra of ligand exhibited peaks at δ 137.31 and 135.59 presumably due to the phenolic (C-O) and imino (-CH=N) carbon atoms (due to Keto-imine tautomerism). The chemical shifts of the aromatic carbons appeared at δ 123.76, 123.09, 122.41, 122.25 and 119.53.

Fig 6.9. 1H-NMR spectrum of LH ( 2d ).

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Fig 6.10. 13 C-NMR spectrum of LH ( 2d ).

6.3.4. Molar conductance measurements

The molar conductance of the complexes ( Λm) was determined by using the relation Λm = 1000× κ/c, where c and κ stands for the molar concentration of the metal complexes and specific conductance, respectively. The complexes (1 × 10 −3 M) were dissolved in N, N -dimethylformamide (DMF) and their specific conductance was measured at (298.15 ±0.01) K. The conductance values were in the range of 134, 131 and 130 S cm -1mol -1 respectively for the metal complexes ( 3d, 4d and 5d ), indicating their 1:2 electrolytic behaviour. 6.3.5. Electronic absorption spectral and magnetic moment studies The UV-Visible spectra of the ligand and the metal complexes (as depicted in Fig 6.11.) were recorded at ambient temperature using methanol as solvent. The electronic spectrum of LH ( 2d ) exhibited three absorption bands at 336, 250 and 218 nm due to n →π*, π→π * and transitions involved with the imidazolium moiety, respectively [42, 43]. For the complexes, the bands that appeared below 350 nm were ligand centred transitions (n →π* and π→π *). The Co(II) complex ( 3d ) displayed a 2 1 1 band at 394 nm which could be assigned to the combination of B1g → A1g and B1g

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2 → Eg transitions and supporting square planar geometry [44, 45]. The complex ( 3d ) showed magnetic moment of 2.30 B.M. due to one unpaired electron. The Ni(II) 1 1 complex ( 4d ) was diamagnetic and the band around 400 nm due to A1g → B1g transition is consistent with low spin square planar geometry [46]. UV-visible spectra of Cu(II) complex ( 5d ) showed d →π* metal-ligand charge transfer transition (MLCT) 2 2 2 in the region 396 nm had been assigned to the combination of B1g → Eg and B1g 2 → B2g transitions in a distorted square planar environment [47, 48]. The experimental magnetic moment for Cu(II) complex ( 5d ) was 1.82 B.M. consistent with the presence of an unpaired electron [49].

Fig 6.11. . UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): (A) LH ( 2d ); (B) Co(II) complex ( 3d ); (C) Ni(II) complex ( 4d ) and (D) Cu(II) complex ( 5d ).

6.3.6. Antibacterial activities Minimum inhibitory concentration was measured by Broth Micro dilution susceptibility method. Serial dilutions of sample solutions were made in nutrient broth medium. Then 1 mL of standard (0.5 McFarland ) bacteria suspension was inoculated

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Table 6.1. Antibacterial activity data of Schiff base ( 2d ) and its metal complexes ( 3d, 4d and 5d ) against E. Coli, S. aureus and B.cereus .

Concentration ( µg/mL) Specimen E. coli S. aureus B.cereus 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 LH (2d) 7 9 12 14 16 7 10 12 15 18 8 10 12 15 17 Co(II) - - 6 7 8 - 6 7 7 9 - 7 8 9 10 complex (3d) Ni(II) 6 8 9 10 12 6 8 9 12 14 - - - 6 7 complex (4d) Cu(II) - 6 7 8 9 - 6 7 7 9 - 7 8 9 10 complex (5d)

Table 6.2. Antibacterial activity data of Schiff base ( 2d ) and its metal complexes ( 3d, 4d and 5d ) against P. aeruginosa, P. vulgaris and E. aerogenes.

Concentration ( µg/mL) Specimen P. aeruginosa P. vulgaris E. aerogenes 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 LH (2d) 9 12 17 20 21 10 12 14 15 19 - - - 6 6 Co(II) - - 7 8 10 6 8 9 10 15 7 8 12 14 14 complex (3d) Ni(II) - 6 7 9 11 7 8 9 9 10 7 10 11 11 13 complex (4d) Cu(II) - - 6 7 7 - - 6 6 8 - - - - 6 complex (5d) into each of these tubes. A similar nutrient broth tube without sample was also inoculated and used as control. The tubes were kept at 37 oC for 24 hours. The lowest concentration of sample which inhibited bacterial growth was considered as minimum inhibitory concentration. Final confirmation was done by streaking on nutrient agar medium. The samples under study showed promising result against all the bacterial strains. (Data was given in Table 6.1 and Table 6.2) From the inhibitory values it was clear that the ligand ( 2d ) was most effecting against five organisms (MIC 10 µg/mL)

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Fig 6.12 . Inhibition zones for the LH ( 2d ), Co(II) complex ( 3d ), Ni(II) complex ( 4d ) and Cu(II) complex ( 5d ). except E. aerogenes . Co(II) complex ( 3d ) was most effective against P. vulgaris and E. aerogens . Ni(II) complex ( 4d ) was observed very active against E. coli, S. aereus, P. aeruginosa and E. aerogenes (MIC 10 µg/mL). The Cu(II) complex ( 5d ) was most effective against E. coli, S. aereus, B. cereus (MIC value 20 µg/mL) and against P. aeruginosa , P. vulgaris (MIC value 30 µg/mL). The result was shown in Fig 6.12. 6.4. Conclusion Herein this chapter the synthesis and physico-chemical characterization of Co(II), Ni(II) and Cu(II) complexes bearing an ionic liquid-supported Schiff base ligand 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate have been reported. The Schiff base and metal complexes were characterized by spectral and analytical methods. The spectral and magnetic susceptibility measurements suggested that the bidentate ligand coordinated to the central metal ion through the azomethine nitrogen and phenolic oxygen atoms,

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yielding square planar complexes. The synthesized complexes and ligand showed reasonable antibacterial activity against the tested gram positive/negative bacteria. References [1] M.J. Earle, J.M.S.S. Esperanc, M.A. Gilea, J.N.C. Lopes, L.P.N. Rebelo, J. Magee, K.R. Seddon, J.A. Widegren. Nature., 439 (2006) 831. [2] H. Sakaebe, H. Matsumoto, Electrochem. Commun., 5 (2003) 594. [3] R.D. Rogers, K.R. Seddon, Science., 302 (2003) 792. [4] R. Sheldon, Green Chem., 7 (2005) 267. [5] P. Wasserscheid, W. Keim., Angew. Chem., Int. Ed. 39 (2000) 3773. [6] P.T. Anastas, J.C. Warner, Green Chemistry-Theory and Practice; Oxford University Press Inc.: New York, 1998. [7] A.E. Visser, R.P. Swatloski, W.M. Reichert, R. Mayton, S. Sheff, A. Wierzbicki, Jr. J.H. Davis, R.D. Rogers, Chem Commun., 1 (2001) 135. [8] Y. Zhou, M. Antonietti, Adv. Mater., 15 (2003) 1452; b) A. Taubert, Z. Li, Dalton Trans., 7 (2007) 723. [9] F. Endres, M. Bukowski, R. Hempelmann, H. Natter, Angew. Chem., 115 (2003) 3550; b) A.P. Abbott, G. Capper, B.G. Swain, D.A. Wheeler, Trans. Inst. Met. Finish., 83 (2005) 51. [10] W. Miao, T.H. Chan,. Acc. Chem. Res., 39 (2006) 897. [11] A. Kamal, G. Chouhan., Tetrahedron Lett., 46 (2005) 1489. [12] S. Lee, Chem. Commun., 10 (2006) 1049. [13] S. Luo, X. Mi, L. Zhang, S. Liu, H. Xu, J.-P. Cheng, J.-P. Tetrahedron., 63 (2007) 1923. [14] E.D. Bates, R.D. Mayton, I. Ntai. J.H. Davis, J. Am. Chem. Soc., 124 (2002) 926. [15] F. D’Anna, S. Marullo, R. Noto, J. Org. Chem., 73 (2008) 6224. [16] J.H. Davis Jr., Chem. Lett., 33 (2004) 1072. [17] S. Tang, A. Babai, A.V. Mudring, Angew. Chem., 120 (2008) 7743. [18] S.A. Patel, S. Sinha, A.N. Mishra, B.V. Kamath, R.N. Ramb, J. Mol. Catal. A., 192 (2003) 53. [19] Y. Peng, Y. Cai, G. Song, J. Chen, Synlett., 14 (2005) 2147. 0 [20] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 235.

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[21] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 1384. [22] S.A. Patil, V.H. Naik, A.D. Kulkarni, P.S. Badami, Spectrochim Acta A., 75 (2010) 347. [23] R. Dinda. Saswati, C.S. Schmiesing, E. Sinn, Y.P. Patil, M. Nethaji, H. Stoeckli- Evans, R. Acharyya, Polyhedron., 50 (2013) 354. [24] M. Yamada, K. Araki, S. Shiraishi, J. Chem Soc. Perkin Trans., 1 (1990) 2687. [25] R.A. Sheldon, I.W.C.E. Arends, H.E.B. Lempers, Catal Today., 41 (1998) 387. [26] R.K. Grasselli, Catal Today., 49 (1999) 141. [27] G. Song, Y. Cai, Y. Peng, J. Comb. Chem.,7 (2005) 561. [28] B. Li, Y.-Q. Li, W.-J. Zheng, M.-Y. Zhou, Arkivoc., IX (2009) 165. [29] Clinical and Laboratory Standards Institute (NCCLS), Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, 9 th ed. M2-A9, Wayne, PA., (2006). [30] Clinical and Laboratory Standards Institute (NCCLS), Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard, 7 th ed. M7-A7, Wayne, PA., (2006). [31] M. Yıldız, Z. Kılıc, T. Hökelek, J. Mol. Struct., 1 (1998) 441. [32] G.-Y. Yeap, S.-T. Ha, N. Ishizawa, K. Suda, P.-L. Boey, W.A.K. Mahmood, J. Mol. Struct., 658 (2003) 87. [33] S.A. Abdel-Latif, H.B. Hassib, Y.M. Issa, Spectrochimica Acta Part., 67 (2007) 950. [34] J. Wang, Y. Pei, Y. Zhao, Z. Hu, Green Chem., 7 (2005) 196. [35] D. Han, K.H. Row, Molecules., 15 (2010) 2405. [36] G.A. Kohawole, K.S. Patel, J. Chem. Soc., Dalton Trans., 6 (1981) 1241. [37] M.A. Mahmoud, S.A. Zaitone, A.M. Ammar. S.A. Sallam, J. Mol Struct., 1180 (2006) 60. [38] D.M. Adams, Metal-Ligand and Related Vibrations: A Critical Survey of the Infrared and Raman Spectra of Metallic and Organometallic Compounds, Edward Arnold (Publishers) Ltd London, England., (1967). [39] M.K. Muthayala, A. Kumar, ACS Comb. Sci., 14 (2012) 5.

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[40] P. Nehra, B. Khungar, K. Pericherla, S.C. Sivasubramanian, A. Kumar, Green Chem., 14 (2014) 4266. [41] B. Li, Y.-Q. Li, W.-J. Zheng, M.-Y. Zhou, Arkivoc., 11 (2009) 165. [42] R.M. Silverstein, ‘Spectrometric Identification of Organic Compounds’, 7 th ed., John Wiley & Sons, (2005). [43] F. Peral, E. Gallego, J. Mol. Struc., 415 (1997) 187. [44] M. Shakir, O.S.M. Nasam, A.K. Mohamed. S.P. Varkey, Polyhedron., 15 (1996) 1283. [45] L.S. Chem, S.C. Cummings, Inorg. Chem. 17 (1978) 2358. [46] A.A. Del Paggio, D.R. McMillin, Inorg. Chem., 22 (1983) 691. [47] C. Natarajan, P. Tharmaraj, R. Murugesan, J. Coord.Chem., 26 (1992) 205. [48] S. Dehghanpour, N. Bouslimani, R. Welter, F. Mojahed., Polyhedron., 26 (2007)154. [49] A.B.P. Lever, ‘Inorganic Electronic Spectroscopy’, 2 nd ed. Elsevier, Amsterdam, (1984).

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Synthesis, Physico-chemical Characterization and Antibacterial Studies of Fe(III) and Cr(III) Complexes with an Ionic Liquid- Supported Schiff Base Ligand

7.1. Introduction Ionic liquids (ILs) are molten salts (melting point below 100 °C) composed of inorganic or organic anions paired with large, usually asymmetric organic cations. Practically, most of ILs remain liquid state at room temperature and are defined as room temperature ionic liquids (RTILs). ILs possess unique physicochemical and solvation properties that can be tuned for specific applications and often give interesting results when employed instead of traditional molecular solvents [1, 2]. In addition, most ILs pose several unique properties, such as negligible vapor pressure [3], no miscibility with nonpolar solvents and high thermal and chemical stability [4- 6]. In recent years, they have received considerable attention because of their wide electrochemical window such as high ionic conductivity [7] and a broad temperature range of the liquid state. Moreover, the physical properties of ILs including density, melting point, polarity, Lewis acidity, viscosity and enthalpy of vaporization can be tuned by changing the cation and anion pairing [8]. IL-based solvent system typically exhibits enhanced reaction kinetics resulting in the efficient use of time and energy [1]. Due to these properties they are considered as a new generation of solvent for catalysis, ecofriendly reaction media for organic synthesis and a successful replacement for conventional media in chemical processes [1, 9]. Recently, many workers have focused on the preparation of new ionic liquids with different functional groups in the cationic moiety, called functionalized ionic liquids (FILs) and their application in chemical research [10-15]. Such functionalization of the cations can easily be done in a single reaction step and thus both the cationic and anionic moieties of the FILs can be altered as required for specific applications [16, 17]. Schiff bases are termed as ‘privileged ligands’ as they are synthesized easily by the condensation between aldehydes and imines. They play key role in coordination chemistry, particularly for having varied denticities, chelating capability

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[18-20] and functionalities [21]. Schiff bases are reported to exhibit different types of biological actions such as antibacterial, antifungal and herbicidal activities due to the presence of azomethine linkage (-CH=N). In case of ionic liquid-supported Schiff- bases, they are attached to imidazolium tags and containing hetero-atoms such as N, O and S to coordinate with metal ions and having unusual configurations [22-24]. Transition metal complexes with Schiff base ligand exhibit variety of applications including biological, medicinal and analytical in addition to their roles in organic synthesis and catalysis. The present chapter deals with the synthesis and physico- chemical characterizations of an ionic liquid-supported Schiff base ligand 1-{2-(2- hydroxy-5-bromobenzylamine)ethyl}-3-ethylimidazolium tetrafluoroborate and its Fe(III) and Cr(III) complex. The synthesized compounds were characterized by various analytical and spectroscopic methods. The Schiff base and its complexes were screened for their in vitro antibacterial activity against gram negative bacterium Escherichia coli and gram positive bacterium Staphylococcus aureus. 7.2. Experimental Section 7.2.1. Materials and Methods All the reagents were of analytical grade and used without further purification. 1-ethyl imidazole, 2-bromoethylamine hydrobromide and sodium tetrafluoroborate were procured from Sigma Aldrich, Germany. 5-bromo-2-hydroxybenzaldehyde, anhydrous FeCl 3, CrCl 3.6H 2O and all other chemicals were used as received from SD Fine Chemicals, India. The solvents methanol, petroleum ether, chloroform, DMF and DMSO were used after purification by the standard methods describe in the literature. The functionalized ionic liquid, 1-(2-aminoethyl)-3-ethylimidazolium tetrafluoroborate, [2-aeeim]BF 4 (1c ) was prepared by following a literature procedure [25]. The synthesis and physicochemical characterization of the FIL have been described earlier in chapter II. FT-IR spectra were recorded in KBr pellets with a Perkin-Elmer Spectrum FT- IR spectrometer (RX-1) operating in the region 4000 to 400 cm -1. 1H-NMR and 13 C- NMR was recorded at room temperature on a FT-NMR (Bruker Avance-II 400 MHz) spectrometer by using DMSO-d6 and D 2O as solvents. Chemical shifts are quoted in ppm downfield of internal standard tetramethylsilane (TMS). Elemental microanalyses (C, H and N) were conducted by using Perkin–Elmer (Model 240C)

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Chapter VII analyzer. Metal content was determined with the aid of AAS (Varian, SpectrAA 50B) by using standard metal solutions procured from Sigma-Aldrich, Germany. Mass spectra were recorded on a JMS-T100LC spectrometer using methanol as solvent. The purity of the prepared compounds was confirmed by thin layer chromatography (TLC) on silica gel plates and the plates were visualized with UV-light and iodine. The UV-Visible absorption spectra were recorded in methanol with a JascoV-530 double beam spectrophotometer at room temperature. SEM images were taken in JEOL-JSM-IT-100 spectrometer. Specific conductance was measured at (298.15 ± 0.01) K by using Systronic conductivity TDS-308 metre with duly calibrated with 0.1(M) of KCl and a cell of path length 1 cm. Magnetic susceptibilities were measured at room temperature with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1). The melting point of the ligand and complexes were determined by open capillary method. Thermal analysis (TGA) was performed in a temperature range of 25-800 oC (heating rate 10 oC/min) by using Perkin–Elmer thermal analyzer in Al 2O3 crucible under N 2 atmosphere. Antibacterial activities ( in vitro ) of the synthesized compounds were tested by well diffusion method against Staphylococcus aureus and Escherichia coli by using Ampicillin as the reference antibiotic. 7.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2d) The detailed synthesis procedure has been discussed earlier in chapter VI. The precipitate was filtered, washed with cold ethanol and dried to afford the expected ligand as a light yellow solid. 3.03 g (yield 75 %). M.p.: 98-100 ºC; Anal. Calc. for

C14 H17 N3OBBrF 4 (410): C, 41.01; H, 4.18; N, 10.25. Found: C, 40.91; H, 4.11; N, 10.21 %. FT-IR (KBr, cm -1): 3449 (O-H), 1673 (C=N), 1276 (C-O), 1114 (B-F). 1H

NMR: (400 MHz, DMSO-d6): δ 2.49 (s, 3H, CH 3), 3.82 (t, 1H, N-CH2), 3.99 (t, 1H,

N-CH2), 4.52 (t, 1H, N-CH2), 6.91–6.85 (m, 3H, Ar-H), 7.33 (s, 1H, NCH), 7.42 (s, 1H, NCH), 8.50 (s, 1H, N=CH), 7.73 (s, 1H, N(H)CN), 9.10 (s, 1H, OH). 13 C NMR

(400 MHz, DMSO-d6): δ 137.31, 135.59, 123.76, 123.09, 122.41, 122.25, 119.63, 53.91, 48.52, 48.14, 44.99, 43.71, 41.15, 35.90. UV-Vis (Methanol) λmax/nm: 218, + + 250, 336. ESI-MS (CH 3OH, m/z): 322 ([M-H-BF 4] , M= [C 14 H17 N3OBr] ).

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7.2.3. Synthesis of the metal complexes (6d and 7d) The complexes were prepared by taking metal salt and ligand in 1:2 molar ratio. The ligand, LH (2.05 g, 5 mmol) was taken in a round bottomed flask equipped with air condenser and dissolved it in 20 mL EtOH. FeCl 3 (0.405 g, 2.5 mmol) or

CrCl 3.6H 2O, (0.66 g, 2.5 mmol) also in the same solvent was added and refluxed the mixture for 4 h until the starting materials were completely consumed as monitored by TLC. Solvents were evaporated and the reaction mixture was cooled to room temperature. The precipitate was obtained by filtration, washed with cold C 2H5OH (10 mL × 3), dry ether (10 mL × 3) respectively and finally dried in desiccators to collect the solid product. The complexes are soluble in N,N-dimethylformamide, dimethylsulphoxide, acetonitrile, methanol and water. A schematic representation of the syntheses is shown in Scheme 7.1.

Scheme.7.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy-5- bromobenzylamine)ethyl}-3-ethylimidazolium tetrafluoroborate ( 2d ), and its M(III) complexes ( 6d and 7d ) from ( 2d ).

7.2.2.1. Fe(III) complex ( 6d ): Brown solid, 3.2 g (yield, 69%), M. p.> 270 oC.

Anal. Calcd. for C 28 H34 FeB 2Br 2ClF 8N6O3 (927): C, 36.27; H, 3.70; N, 9.06; Fe, 6.02. -11 Found: C, 36.12; H, 3.63; N, 9.01, Fe, 6.01 %. FT-IR (KBr, cm ): 3422 (O-H/H 2O), 2933 (Ar-H), 2863 (C-H), 1671 (C=N), 1279 (C-O), 1116 (B-F), 535 (M-N), 449 (M-

O). UV-Vis (Methanol) λmax/nm: 205, 227, 387. ESI-MS: (CH 3OH, m/z ) =733 [M- + 2BF 4-H2O] .

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Fig 7.1. SEM image of Fe(III) complex ( 6d )

7.2.2.2. Cr(III) complex ( 7d ): Light green solid; 3.3 g (yield, 73%). M. p.> o 270 C. Anal. Calc. for C 28 H34 CrB 2Br 2ClF 8N6O3 (923.43): C, 36.42; H, 3.71; N, 9.10, Cr, 5.63. Found: C, 36.35; H, 3.56; N, 9.02 %, Cr, 5.62 %. FT-IR (KBr, cm -1): 3438

(O-H/H 2O), 2926 (Ar-H), 2867 (C-H), 1670 (C=N), 1278 (C-O), 1112 (B-F), 538 (M-

N), 446 (M-O). UV-Vis (Methanol) λmax/nm: 219, 338, 400. ESI-MS: (CH 3OH, + m/z ) =730 [M-2BF 4-H2O] .

Fig 7.2. SEM image of Cr(III) complex ( 7d ).

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7.3. Results and Discussion All the isolated compounds were found to be air stable and were characterized by different analytical and spectroscopic methods. 7.3.1. FT-IR spectra The FT-IR spectra of the complexes were compared with the ligand (LH) in order to determine the coordination sites involved in chelation. The ligand showed a strong broad band at 3449-3230 cm -1; that was assigned to the hydrogen bonded -OH of the phenolic group with H–C(=N) group of the ligand (OH…N=C) [26, 27]. The broad band at 3422-3438 cm -1 in the spectra of Fe(III) and Cr(III) complexes respectively proposed the presence of coordinated water molecule. However, these bands appeared stronger compare to that of the ligand due to the moisture content of the ligand subject to the intrinsic nature of the anion tetrafluoroborate [28-30]. For the LH ( 2a ) a band corresponding to the azomethine group (-C=N) was found at 1675 cm - 1. On complexation, this band gets shifted to lower wave number range 1671-1670 cm -1. This indicated the involvement of N-atom of azomethine (-C=N) group in the complex formation [31]. The band for phenolic C-O of free ligand was observed at 1274 cm -1. Upon complexation, this band was moved to higher wave number 1279- 1278 cm -1 for the complexes 6d and 7d . This fact assigned the coordination of ligand to metal atom by the azomethine nitrogen and phenolic oxygen atom [32]. The bands appeared in the range of 1116-1112 cm -1 in the spectra of ligand and metal complexes were assigned for B-F stretching frequency. In the spectra of the complexes, bands observed at 535-538 and 449-446 cm -1 were attributed to M-O and M-N stretching vibrations, respectively. The band due to M-Cl, expected to appear at around 320-250 cm -1, which was beyond the experimental IR range [33, 34]. FT-IR spectra of the Schiff base, LH ( 2d ) and its metal complexes ( 6d ) and ( 7d ) were given in Figs 7.3- 7.5.

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Fig 7.3. FT-IR spectrum of LH ( 2d ).

Fig 7.4. FT-IR spectrum of Fe(III) complex ( 6d ).

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Fig 7.5. FT-IR spectrum of Cr(III) complex ( 7d ).

7.3.2. Mass spectra The mass spectra of the Fe(III) complex ( 6d ) showed peaks ( m/z ) at 733 and Cr(III) complex ( 7d ) displayed peaks ( m/z ) at 730 which was assigned to the [M- + + 2BF 4-H2O] ion where M=.[C28 H32 FeBr 2ClN 6O2] for ( 6d) and M=. + [C28 H32 CrBr 2ClN 6O2] for ( 7d) respectively. These spectra of the complexes (shown in Fig. 7.6. and Fig.7.7.) were in good agreement with the respective structures as revealed by the elemental and other spectral analyses.

Fig 7.6. ESI-MS spectrum of Fe(III)complex ( 6d ).

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Fig 7.7. ESI-MS spectrum of Cr(III)complex ( 7d ).

7.3.3. 1H-NMR and 13 C-NMR spectra 1H-NMR of the ligand ( 2d ) showed a singlet at δ 8.50 ppm that was assigned for the proton of the azomethine group (-CH=N-) most probably owing to the effect of the ortho -hydroxyl group in the aromatic ring. Another singlet at δ 9.10 ppm was attributed to hydroxyl proton. The LH ( 2d ) displayed downfield shift of the –OH proton was due to intramolecular (O-H...N) hydrogen bonding [35]. 13 C-NMR spectra of LH ( 2d ) exhibited peaks at δ 137.31 and 135.59 tentatively due to the phenolic (C- O) and imino (-CH=N) carbon atoms (due to Keto-imine tautomerism). The chemical shifts involving the aromatic carbons appeared at δ 123.76, 123.09, 122.41, 122.25 and 119.53. 1H-NMR and 13 C-NMR spectra of Schiff base were given as Figs 6.9 and 6.10 in Chapter VI. 7.3.4. Molar Conductance Measurements

The molar conductance of the complexes ( Λm) were determined by using the relation Λm = 1000× κ/c, where c and κ stands for the molar concentration of the metal complexes and specific conductance, respectively. The complexes (10 −3 M) were dissolved in N,N -dimethylformamide and their specific conductance was measured at (298.15 ±0.01) K. The conductance values were 128 and 133 S cm -1mol -1 for Fe(III)

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Chapter VII complex ( 6d ) and Cr(III) complex( 7d ) respectively, indicating their 1:2 electrolytic behaviour. 7.3.5. Electronic spectra and magnetic moment studies The UV-Visible spectra of the ligand ( 2d ) and the metal complexes ( 6d and 7d ) were recorded in methanol at ambient temperature. The electronic spectrum of 2d showed three absorption bands at 318, 255 and 215 nm due to n →π*, π→π * and transitions involved with the imidazolium moiety, respectively [36, 37]. The Fe(III) complex ( 6d ) (d 5 configuration) showed bands at 387, 226 and 205 nm. The weak 6 band in the range 387 nm was assigned to the spin and parity forbidden A1g →T2g transition of Fe(III) ion in an octahedral field. The high spin octahedral Fe(III) complexes had very weak and spin forbidden d-d transition which didn’t appear in the spectra due to the low intensity of the d-d transition. The observed magnetic moment 3 2 of 5.56 B.M. for 6d (theoretical value for Fe(III), t 2g eg system is √35= 5.92) suggested high spin configuration of the metal ion in the Fe(III) complex with five unpaired electrons [38]. UV-visible spectrum of the Cr(III) complex( 7d ) exhibited 4 4 three bands at 400, 340, 220 nm. These bands could be assigned to A2g (F) → T2g (F), 4 4 4 4 A2g (F) → T1g (F) and A2g (F) → T1g (P) transitions, respectively suggesting octahedral geometry around the Cr(III) ion [39, 40]. Again the complex 7d showed magnetic moment of 3.93 B.M. corresponding to three unpaired electrons (theoretical value for 3 Cr(III), t 2g system is √15= 3.88). The UV-Visible spectra were shown in Fig 7.8.

Fig 7.8. UV-visible spectra in methanol (concentration of the solutions 1 × 10 -4 M): (A) LH ( 2d ); (B) Fe(III) complex ( 6d ) and (C) Cr(III) complex ( 7d ).

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7.3.6. Thermal analysis Thermal behaviour of the complexes was studied by TGA (as shown in Fig o 7.9) over a temperature range of 25-800 C in Al 2O3 crucible under N 2 atmosphere. The temperature was programmed to increase linearly at 10 oC/min. TGA thermograms of the Fe(III) and Cr(III) complexes ( 6d and 7d ) showed a first step decomposition around 110 oC with 10-18 % weight loss including the loss of coordinated water molecules and the anion parts of the complexes. At the temperature range 110-160 oC and 160-300 oC the major mass losses occurred due to the decomposition of the organic fragments of the complexes with the formation of different intermediates. These intermediates further decomposed at the temperature range of 300-750 oC followed by elimination of remaining organic parts. The decomposition was completed approximately at 800 oC leading to the formation of the stable metal oxides [28]. The oxides formed were 8.61 % and 5.63 % for 6d and 7d , respectively. These quantities of respective oxides were as per the stoichiometry of the complexes obtained from elemental analysis.

Fig 7.9. TGA of Fe(III) complex ( 6d ) and Cr(III) complex(7d ).

7. 3.7. Antibacterial studies Antibacterial activity of the synthesized compounds was studied in vitro against the gram negative (Escherichia coli) and gram positive (Staphylococcus aureus ) bacterial strains by agar disc diffusion method [41, 42] by NCCLS (National

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Committee for Clinical Laboratory Standards, 1997) and inoculated with 0.5 McFarland standard. The nutrient agar (Hi-Media Laboratories Limited, Mumbai, India) was autoclaved at 121 ˚C and 1 atm for 15-20 minutes. The sterile nutrient media was kept at 45-50˚C, after that 100 µL of bacterial suspension containing 10 8 colony-forming units (CFU)/mL were mixed with sterile liquid nutrient agar and poured into the sterile Petri dishes. Upon solidification of the medium, filter disc (5 mm diameter) was individually soaked with different concentration (10, 20, 30, 40, 50 µg/mL) of each compound and placed on the solidified nutrient agar media plates. The different concentrations were made by dilution with DMSO. Minimum inhibitory concentration was measured by Broth Micro dilution susceptibility method. No inhibition zone was found for the solvent control (DMSO) for each bacterial suspension. A serial dilution of sample compound was made in nutrient broth medium and plates were incubated for 24 hours at 37 ˚C. A similar nutrient broth tube without sample compound was also inoculated to use as control. The ligand was highly active against the E.coli (gram negative) and S. aureus (gram positive) bacteria for the concentrations 20, 30, 40 and 50 µg/mL [43]. In case of metal complexes, the data showed that the Cr(III) complex ( 6d ) was more active than the Fe(III) complex ( 7d ) [44, 45]. Their biological activities were higher that of the Ampicillin antibiotic. The biological assays data was shown in Table 7.1.

Table 7.1. Biological assays data of 1-{2-(2-hydroxy-5-bromobenzylamine)ethyl}-3- ethylimidazolium tetrafluoroborate ( 2d ); Fe(III) complex ( 6d ) and Cr(III) complex (7d ) against E. coli and S. aureus. Concentration Specimen E. coli S. aureus 10 20 30 40 50 10 20 30 40 50 Ligand (2d) 7 9 12 14 16 7 10 12 15 18 Fe(III) complex (6d) 0 0 6 7 10 0 6 7 8 9 Cr(III) complex (7d) 6 8 9 10 12 6 8 9 12 14 Control 0 0 0 0 0 0 0 0 0 0 Ampicillin 0 0 6 6 8 0 0 6 8 8

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Fig 7.10. MIC of the Fe(III) complex ( 6d ) and Cr(III) complex ( 7d ) against S. aureus.

7. 4. Conclusion Herein this study an ionic liquid-supported Schiff base 1-{2-(2-hydroxy-5- bromobenzylamine)ethyl}-3-ethylimidazolium tetrafluoroborate and its Fe(III) and Cr(III) complexes were synthesized and characterized by different spectral and analytical results. These data suggest distorted octahedral geometry for both the metal complexes. The Schiff base acts as a bidentate ligand coordinating through the azomethine nitrogen and phenolic oxygen atom to the metal ions and thus formed 1:2 (M:L) complexes with Fe(III) and Cr(III) ions. The synthesized complexes along with the ligand were tested for their in vitro antibacterial activities. A detectable antibacterial activity was observed in case of the Schiff base ligand and Cr(III) complex against the tested bacteria Escherichia coli and Staphylococcus aureus. References [1] T. Welton, Chem. Rev., 99 (1999) 2071. [2] C. Chiappe, D. Pieraccini, J. Org. Chem., 69 (2004) 6059. [3] M.J. Earle, J.M S.S. Esperanc, M.A. Gilea, J.N.C. Lopes, L.P.N. Rebelo, J. Magee, K.R. Seddon, J.A. Widegren, Nature., 439 (2006) 831. [4] R.D. Rogers, K.R. Seddon, Science., 302 (2003) 792.

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[5] R. Sheldon, Green Chem., 7 (2005) 267. [6] P. Wasserscheid, W. Keim, Angew. Chem., Int. Ed., 39 (2000) 3772. [7] H. Sakaebe, H. Matsumoto, Electrochem. Commun., 5 (2003) 594. [8] M.G. Freire, L.M.N.B.F. Santos, A.M. Fernandes, J.A.P. Coutinho, I.M. Marrucho, Fluid Phase Equilibr., 261 (2007) 449. [9] R. Sheldon, Chem. Commun., 23, 2399 (2001). [10] F. Yi, Y. Peng, G. Song, Tetrahedron Lett., 46 (2005) 3931. [11] E.D. Bates, R.D. Mayton, I. Ntai. J.H. Davis, J. Am. Chem. Soc., 124 (2002) 926. [12] A.C. Cole, J.L. Jensen, I. Ntai, K.L.T. Tran, J. Am. Chem. Soc., 124 (2002) 5962. [13] J. Li, Y. Peng, G. Song, Catal. Lett., 102 (2005) 159. [14] J.H. Davis Jr., K.J.T. Forrester, J. Merrigan, Tetrahedron Lett., 49 (1998) 8955. [15] J.J. Jodry, K. Mikami, Tetrahedron Lett., 45 (2004) 4429. [16] Z. Fei, T.J. Geldbach, D. Zhao, P.J. Dyson, J. Eur. Chem., 12 (2006) 2122. [17] S.G. Lee, Chem. Commun., 14 (2006) 1049. [18] S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 235. [19] A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Coord. Chem. Rev., 253 (2009) 1384. [20] C.M. Liu, R.G. Xiong, X.Z. You, Y.J. Liu, K.K. Cheung, Polyhedron., 15 (1996) 4565. [21] A.J. Atkins, D. Black, A.J. Blake, A. Marin-Bocerra, S. Parsons, L. Ruiz-Ramirez, M. Schröder, Chem. Commun., (1996) 457. [22] A. Goku, M. Tumer, H. Demirelli, R.A. Wheatley, Inorg. Chim. Acta., 358 (2005) 1785. [23] A.M. Mahindra, J.M. Fisher, Rabinovitz, Nature., 303 (1983) 64. [24] P.R. Palet, B.T. Thaker, S. Zele, Indian. J. Chem. A., 38 (1999) 563. [25] G. Song, Y. Cai, Y. Peng, J. Comb. Chem., 7 (2005) 561. [26] M. Yıldız, Z. Kılıc, T. Hökelek, J. Mol. Struct., 1 (1998) 441. [27] G.-Y. Yeap, S.-T. Ha, N. Ishizawa, K. Suda, P.-L. Boey, W.A.K. Mahmood, J. Mol. Struct., 658 (2003) 87. [28] S.A. Abdel-Latif, H.B. Hassib, Y.M. Issa, Spectrochimica Acta Part A., 67 (2007) 950. [29] J. Wang, Y. Pei, Y. Zhao, Z. Hu, Green Chem., 7 (2005) 196.

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[30] D. Han, K.H. Row, Molecules., 15 (2010) 2405. [31] G.A. Kohawole, K.S. Patel, J. Chem. Soc., Dalton Trans., 6 (1981) 1241. [32] M.A. Mahmoud, S.A. Zaitone, A.M. Ammar. S.A. Sallam, J. Mol Struct., 1108 (2006) 60. [33] O.M.I. Adly, A. Taha, S.A. Fahmy, J. Mol. Struct., 1054 (2013) 239. [34] N.K. Kar, M.K. Singh, R.A. Lal, Arabian Journal of Chemistry., 5 (2012) 67. [35] B. Li, Y.-Q. Li, W.-J. Zheng, M.-Y. Zhou, Arkivoc., 11 (2009) 165. [36] R.M. Silverstein, Spectrometric Identification of Organic Compounds, 7 th ed., John Wiley & Sons, (2005). [37] F. Peral, E. Gallego, J. Mol. Struc., 415 (1997) 187. [38] A.D. Kulkarni, S.A. Patil, P.S. Badami, Int. J. Electrochem. Sci., 4 (2009) 717. [39] K. Dey, K. Chakraborty, Indian J Chem., 39A (2000) 1140. [40] A.B.P. Lever, Inorganic Electronic Spectroscopy, 2 nd ed, Elsevier, Amsterdam, (1984). [41] Clinical and Laboratory Standards Institute (NCCLS), Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, 9 th ed., M2-A9, Wayne, PA, (2006). [42] Clinical and Laboratory Standards Institute (NCCLS), Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: Approved Standard, 7 th ed., M7-A7, Wayne, PA, (2006). [43] B. Khungar, M.S. Rao, K. Pericherla, P. Nehra, N. Jain, J. Panwar, A. Kumar, C. R. Chimie. 15 (2012) 669. [44] R.K. Barid, M.L. Al-Dokheily, I.A. Flifel, Global Journal of Pure and Applied Chemistry Research., 2 (2014) 1. [45] H.F. Abd El-Halima, G.G. Mohamedb, M.M.I. El-Dessoukya, W.H. Mahmoudb, Spectrochimica Acta Part A. 82 (2011) 8.

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Synthesis, Physico-chemical characterization and potential biological applications of Transition metal complexes obtained from an ionic liquid-supported Schiff base ligand: 1-{2-(2-hydroxy-5-chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate

8.1. Introduction The search of environmentally benign nonaqueous solvents, that could easily be recovered or recycled and the use of efficient and selective catalyst are two of the main aims for the development of sustainable and green chemical process [1]. Ionic liquids (ILs), which are the new class of solvents, also termed as neoteric solvents that leads to a new green chemical revolution. Their unique array of physical-chemical properties along with negligible vapor pressure makes ILs suitable for varrious applications [2]. These new solvents are also termed as room temperature ionic liquids (RTILs) or liquid organic salts. ILs are a class of substances that are entirely made of ions (cations and anions) and are liquid at temperature lower than 100 ˚C. They have many attractive features, including low flammability, a wide liquid range, high ionic conductivity, high thermal and chemical stability, good dissolution power toward many substrates and wide electrochemical windows [3, 4]. Owing to these attracting properties, ILs have been recognized as solvents or reagents for variety of applications, including organic catalysis [5-10], inorganic synthesis [11], biocatalysis [12-16], polymerization [17,18] and engineering fluids [19-20]. Again due to their designable properties, ILs have recently been exploited as solvents or materials for variety of pharmaceutical applications [21-22]. Recently, chemists have focused much attention on the synthesis, characterization and application of new ionic liquids called functionalized ionic liquids (FILs). FILs are defined as ionic liquids in which functional group are covalently attached to the cation or anion (or both). Conceptually, the functionalized ion of a FILs may be regarded as possessing two elements. The first is a core that contains the ionic charge and behaves as the locus for the second element i.e. the substituent group [23-25]. In most of the cases the functional group is cation-tethered. The introduction of this type of functionality can

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Chapter VIII imbue the salt with an ability to act as a reaction medium as well as a catalyst or reagent in some chemical reactions [26, 27]. Schiff bases and its transition metal complexes have captured a crucial role in the progress of modern coordination chemistry. They are also being found as key material in the growth of inorganic biochemistry, catalysis, optical materials etc [28]. At present, transition metal complexes derived from multidentate unsymmetrical

Schiff base ligands carrying both –NH2 (amine) and –OH (hydroxyl) groups have drawn much attention [29]. Schiff base complexes catalyze a wide number of heterogeneous and homogeneous reactions and their activities may be altered by varying metal ions, coordination sites and the ligand nature [30]. Schiff base ligands having N, S and O as donor atoms exhibit wide range of biological applications and are gained special interest due to the number of ways they can bonded to the metal ions [31]. In this chapter the synthesis, physico-chemical characterization and biological studies of new transition metal complexes derived from an ionic liquid- supported Schiff base, 1-{2-(2-hydroxy-5-chlorobenzylideneamino)ethyl}-3- methylimidazolium tetrafluoroborate have been discussed. 8.2. Experimental Section 8.2.1. Materials and Methods Analytical grade chemicals were used for synthesis without further purification. 1-methyl imidazole, 2-bromoethylamine hydrobromide, 5-chloro-2- hydroxybenzaldehyde and NaBF 4 (sodium tetrafluoroborate) were collected from Sigma Aldrich, Germany. Metal acetates and metal chlorides were used as obtained from SD Fine Chemicals, India. CH 3OH, petroleum ether, CHCl 3, DMF and DMSO were used after purification by standard methods described in the literature. The FIL,

1-(2-aminoethyl)-3-methylimidazolium tetrafluoroborate, [2-aemim]BF 4 (1d ) was prepared by following a literature procedure [32]. The synthesis and structural characterization of the FILs (1d ) have been described earlier in chapter II. FT-IR spectra were recorded by KBr pellets on a Perkin-Elmer Spectrum FT- IR spectrometer (RX-1). 1H-NMR spectra were recorded on a FT-NMR (Bruker

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Elemental microanalysis (CHN analysis) was performed on Perkin–Elmer (Model 240C) analyzer. Metal content was obtained from AAS (Varian, SpectrAA 50B) by using standard metal solutions procured from Sigma-Aldrich, Germany. Mass spectra were obtained on a JMS-T100LC spectrometer. The purity of the synthesized products was confirmed by thin layer chromatography (TLC, Merck 60 F254 silica gel plates, layer thickness 0.25 mm) and the spots were visualized using UV-light. The UV-Visible spectra were obtained from JascoV-530 double beam

Spectrophotometer using CH 3OH as solvent. Specific conductance was measured at (298.15 ± 0.01) K with a Systronic conductivity TDS-308 metre. Magnetic susceptibility was measured with a Sherwood Scientific Ltd magnetic susceptibility balance (Magway MSB Mk1) at ambient temperature. The melting point of synthesized compounds was determined by open capillary method. Antibacterial activity ( in vitro ) of the synthesized ligand and complexes were evaluated by well diffusion method against four bacterial strains (Two gram positive and two gram negative). 8.2.2. Synthesis of imidazolium ionic liquid-supported Schiff base, LH (2e)

5-chloro-2-hydroxybenzaldehyde (1.57 g, 10 mmol) and [2-aeeim]BF 4 (2.13 g, 10 mmol) were taken in a round bottomed flask and methanol was used as solvent. The reaction mixture was stirred at room temperature for 12 h. After completion of reaction, ethanol was used to dilute the solid. The precipitate was filtered, washed with cold ethanol and dried properly to collect the Schiff base as a light yellow solid.

2.57 g (yield, 73 %). M. p. 93-95 ºC. Anal. Calc. for C 13 H15 N3OClBF 4 (351.54): C, 44.42; H, 4.30; N, 11.95. Found: C, 44.14; H, 4.09; N, 11.83 %. FT-IR (KBr, cm -1) 3448 (O-H), 3071, 1665 (C=N), 1279 (C-O), 1106 (B-F). 1H NMR: (400 MHz,

DMSO-d6): δ 2.49 (t, 2H, N-CH2), 3.51 (t, 2H, N-CH2), 4.28 (s, 3H, C H3), 6.97–6.90 (m, 3H, Ar-H), 7.62 (s, 1H, NC H), 7.63 (s, 1H, NC H), 10.18 (s, 1H, N=C H), 7.70 (s, 13 1H, N( H)CN), 9.30 (s, 1H, O H). C NMR: (400 MHz, DMSO-d6): δ 165.81, 142.24, 139.44, 130.53, 124.32, 122.05, 110.01, 39.85, 39.64, 3922, 39.01, 38.80 and 38.60.

UV-Vis (Methanol, λmax): 220, 250, 336 nm; ESI-MS (CH 3OH, m/z): 264 ([M- + + BF 4] , M= [C13 H15 ClN 3O] ).

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8.2.3. Synthesis of the metal complexes (3e, 4e and 5e) To a solution of ligand, ( 2e ) (0.352 g, 1 mmol) in ethanol (20 mL), metal acetate salt Co(II), Ni(II) and Cu(II), viz. , (0.5 mmol) dissolved in ethanol was added gradually in a round bottomed flask. The mixture was refluxed for 4 h until the starting materials were completely consumed as monitored by TLC. After that, solvents were evaporated and the reaction mixture was cooled to room temperature. The solid was collected by filtration, washed successively with cold ethanol (10 mL × 3). Finally it was dried in vacuum desiccators to obtain the desired product. The complexes are soluble in N,N-dimethylformamide, dimethylsulphoxide, acetonitrile, methanol and water. A schematic representation of the synthesis is shown in Scheme 8.1.

Scheme 8.1. Synthesis of the ionic liquid-supported Schiff base, 1-{2-(2-hydroxy-5- chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate ( 2e ), and its metal complexes ( 3e, 4e and 5e ) from ( 2e ).

8.2.3.1. Co(II) complex (3e): Brown solid; 0.53 g (yield, 70 %), decomposes at ~ 253 oC. Anal. Calc. for

C26 H28 CoCl 2B2F8N6O2 (760): 41.09; H, 3.71; N, 11.06, Co, 7.75. Found: C, 40.69; H, 3.41; N, 10.86, Co, 7.62 %. FT-IR (KBr, cm -1): 3438 (O-H), 1628 (C=N), 1316 (C- O), 1075 (B-F), 638 (M-O), 523(M-N). UV-Vis (Methanol, λmax/nm): 220, 340, 401. + + ESI-MS (CH 3OH, m/z): 585 ([M-2BF 4] , M= [(C 26 H28 CoCl 2N6O2] ).

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Fig 8.1. SEM image of Co(II) complex ( 3e )

8.2.3.2. Ni(II) complex (4e): Light green solid; 0.52 g (yield, 69 %), o decomposes at ~ 251 C. Anal. Calc. for C26 H28 NiCl 2B2F8N6O2 (759.75): C, 41.10; H, 3.71; N, 11.06; Ni, 7.26. Found: C, 41.02; H, 3.63; N, 10.46, Ni, 7.19 %. FT-IR (KBr, cm -1): 3453 (O-H), 1628 (C=N), 1322 (C-O), 1012 (B-F), 565 (M-O), 439 (M-N).

UV-Vis (Methanol, λmax/nm): 220, 340, 400. ESI-MS (CH 3OH, m/z): 586 ([M+2H- + + 2BF 4] , M= [(C 26 H28 NiCl 2N6O2] ).

Fig 8.2 . SEM image of Ni(II) complex ( 4e )

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8.2.3.3. Cu(II) complex (5e): Dark green solid; 0.54 g (yield, 71 %), decomposes at ~ 265 oC. Anal. Calc. for

C26 H28 CuCl 2B2F8N6O2 (764.60): C, 40.84; H, 3.69; N, 10.99; Cu, 8.31. Found: C, 40.12; H, 3.51; N, 10.46, Cu, 8.11 %. FT-IR (KBr, cm -1): 3448 (O-H), 1624 (C=N), 1320 (C-O), 1012 (B-F), 651 (M-O), 565 (M-N). UV-Vis (Methanol, λmax/nm): 222, + + 242, 394. ESI-MS (CH 3OH, m/z): 588 ([M-H-2BF 4] , M= [(C 26 H28 CuCl 2N6O2] ).

Fig 8.3. SEM image of Cu(II) complex (5e )

8.2.4. Synthesis of the metal complexes (6e, 7e and 8e) The Schiff base ( 2e ) (1.76 g, 5 mmol) was taken in round bottomed flask abd dissolved in EtOH (20 mL). Mn(CH 3COO)2, 4H 2O (0.61 g, 2.5 mmol) and LiCl (0.15 g, 2.5 mmol) for complex 6e and FeCl 3 (0.405 g, 2.5 mmol) or CrCl 3.6H 2O, (0.66 g, 2.5 mmol) for the complex 7e and 8e respectively, also in the same solvent was added and the reaction mixture was refluxed for 4 h. The reaction was monitored by TLC. On completion of the reaction, solvents were evaporated and cooled to room temperature. The solid was collected by filtration, washed with cold C 2H5OH (10 mL × 3), dry ether (10 mL × 3) respectively and finally dried in desiccators to obtain the desired product. The complexes are soluble in N,N-dimethylformamide, dimethylsulphoxide, acetonitrile, methanol and water. A schematic representation of the syntheses is given in Scheme. 8.2.

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Scheme 8.2. Synthesis of the M(III) complexes ( 6e, 7e and 8e ) from ( 2e ).

8.2.4.1. Mn(III) complex (6e): Light brown solid; 2.7 g (yield, 67%). decomposes at ~ 269 oC. Anal. Calc. for

C26 H30 MnB 2Cl 3F8N6O3 (809.46): C, 38.58; H, 3.74; N, 10.38, Cr, 6.79. Found: C, -1 38.35; H, 3.56; N, 10.12, Cr, 6.52 %. FT-IR (KBr, cm ): 3433 (O-H/H 2O), 1649 (C=N), 1314 (C-O), 1019 (B-F), 651 (M-N), 528 (M-O). UV-Vis (Methanol) + λmax/nm: 216, 244, 340. ESI-MS: (CH 3OH, m/z ) =618 ([M+2H-2BF 4-H2O] , M= + [C26 H28 MnCl 3N6O2] ).

Fig 8.4. SEM image of Mn(III) complex ( 6e ).

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8.2.4.2. Fe(III) complex (7e): Grey solid, 2.8 g (yield, 69%), decomposes at ~ 270 oC. Anal. Calcd. for

C26 H30 FeB 2Cl 3F8N6O3 (810.37): C, 38.54; H, 3.73; N, 10.37; Fe, 6.89. Found: C, -11 38.12; H, 3.63; N, 10.09, Fe, 6.71 %. FT-IR (KBr, cm ): 3430 (O-H/H 2O), 1661 (C=N), 1276 (C-O), 1116 (B-F), 543 (M-N), 453 (M-O). UV-Vis (Methanol) + λmax/nm: 215, 243, 343. ESI-MS: (CH 3OH, m/z ) = 618 ([M-H-2BF 4-H2O] , M= + [C26 H28 FeCl 3N6O2] ).

Fig 8.5. SEM image of Fe(III) complex ( 7e )

8.2.4.3. Cr(III) complex (8e): Light green solid; 2.6 g (yield, 65%). decomposes at ~ 267 oC. Anal. Calc. for

C26 H30 CrB 2Cl 3F8N6O3 (806.52): C, 38.72; H, 3.75; N, 10.42, Cr, 6.45. Found: C, -1 38.42; H, 3.61; N, 10.10, Cr, 6.22 %. FT-IR (KBr, cm ): 3431 (O-H/H 2O), 1660 (C=N), 1276 (C-O), 1116 (B-F), 543 (M-N), 452 (M-O). UV-Vis (Methanol) + λmax/nm: 220, 338, 394. ESI-MS: (CH 3OH, m/z ) = 613 ([M-2BF 4-H2O] , M= + [C26 H28 CrCl 3N6O2] ).

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Fig 8.6. SEM image of Cr(III) complex ( 8e ).

8.4.5. Antimicrobial activity Broth culture of overnight grown four bacterial strains of which two were gram positive ( Staphylococcus aureus and Bacillus cereus ) and the other two gram negative ( Escherichia coli and Klebsiella pneumoniae ) were used for the present study to assess the antimicrobial activities of synthesized samples. Mueller-Hinton agar media (Himedia) was used for susceptibility tests. 38.0 g of MH media was added in 1000 ml of double distilled water and heated to dissolve completely. The media was sterilized by autoclaving at 20 lbs pressure at 121ºC for 20 minutes. The media was cooled down to room temperature and poured in sterile petri plates at sterile condition of Laminar air flow cabinet. 100µl of bacterial strains were added separately to each petriplates containing media and agitated for mixing. 20 mg powdered samples were dissolved in 1000 µL of dimethyl sulfoxide (DMSO). Paper disc diffusion method was applied [33]. Circular paper disc were cut from Whatman 42 filter papers and were dipped in the sample solutions for one hour. The paper discs dipped in sample solutions were placed on the media containing bacterial culture and incubated overnight at 37ºC. 8.3. Results and Discussion All the isolated compounds were stable at room temperature to be characterized by different analytical and spectroscopic methods.

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8.3.1. FT-IR spectral studies In order to justify the coordination sites, the FT-IR spectra of Schiff base ( 2e ) and all the complexes ( 3e-8e ) were studied carefully. FT-IR spectra of LH ( 2e ) showed a strong band at 3448-3071 cm -1; which was due to the hydrogen bonded phenolic group (-OH) with H–C(=N) group in the ligand (OH…N=C) [34, 35]. The broad band appeared at 3453-3430 cm -1 for the metal complexes suggested the presence of the solvated (probably for the intrinsic property of the anion tetrafluoroborate) or coordinated water molecules [36-38]. The band due to the azomethine group (-C=N) of the ligand was found at 1665 cm -1. This band gets shifted in the range 1661-1624 cm -1 because of coordination of N atom of azomethine linkage to the metal ions [39]. The band for phenolic C-O of free ligand was observed at 1279 cm -1 which was moved to the wave number 1322-1276 cm -1 for the complexes after complexation. This fact suggested the bonding of ligand ( 2e ) to the metal atoms through the N atom of azomethine and O atom of phenolic group [40]. The bands appeared in the region of 1116-1012 cm -1 for the ligand and metal complexes were assigned for B-F stretching frequency. The spectra of the metal complexes exhibited bands at 651-543 and 565-439 cm -1 were attributed to M-O and M-N stretching vibrations, respectively [41]. The band due to M-Cl, expected to appear at around 320-250 cm -1, which was beyond the experimental IR range [42, 43]. FT-IR spectra of the Schiff base and its metal complexes are shown in Figs 8.7, Fig 8.8-8.13.

Fig 8.7 . FT-IR spectra of ligand ( 2e ).

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Fig 8.8 . FT-IR spectra of Co(II) complex ( 3e ).

Fig 8.9. FT-IR spectra of Ni(II) complex ( 4e ).

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Fig 8.10. FT-IR spectra of Cu(II) complex (5e).

Fig 8.11. FT-IR spectra of Mn(III) complex (6e).

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Fig 8.12. FT-IR spectra of Fe(III) complex (7e).

Fig 8.13. FT-IR spectra of Cr(III) complex (8e).

8.3.2. 1H and 13 C-NMR spectral studies The 1H-NMR and 13 C-NMR spectra of ligand (Shown in Fig 8.14 and Fig 1 8.15.) were recorded in DMSO-d6. The H-NMR spectrum of ligand (2 e) showed singlet at δ 10.18 ppm corresponds to proton of the azomethine linkage (-CH=N-) apparently because of the effect of the ortho -hydroxyl group in the aromatic ring. A singlet at δ 9.30 ppm was assigned to hydroxyl proton (-OH). The downfield shift of

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Fig 8.14. 1H-NMR spectra of LH( 2e ).

Fig 8.15. 13 C-NMR spectra of LH( 2e ). the phenolic (–OH) proton was observed due to intramolecular (O-H...N) hydrogen bonding in the ligand [44]. 13 C-NMR spectra of ligand exhibited peaks at δ 165.81 and 142.24 probably due to the phenolic (C-O) and imino (-CH=N) carbon atoms (due

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Chapter VIII to Keto-imine tautomerism). The chemical shifts due to the aromatic carbons appeared at δ 139.44-110.01 ppm. 8.3.3. Powder X-ray diffraction analysis The PXRD analysis of the synthesized ligand and metal complexes was carried out to confirm whether the particle nature of the samples was amorphous or crystalline. The PXRD spectrum of ligand ( 2e ) displayed sharp peaks because of their crystalline nature although the spectra of the metal complexes didn’t show such peaks due to their amorphous nature (Figs 8.16-8.22). The crystalline sizes were calculated using Debye Scherer’s equation: D= 0.9 λ/βcos θ, where constant 0.9 is the shape factor, λ is the X-ray wavelength (1.5406 Å), β is the full width at half maximum (FWHM) and θ is the Bragg diffraction angle. The experimental average grain sizes of the Schiff base and its metal complexes were found to be 31.05 nm ( 2e ), 3.96 nm (3e ), 2.56 nm ( 4e ), 3.82 nm ( 5e ) 3.32 nm ( 6e ), 8.91nm ( 7e ) and 11.94 nm ( 8e ).

Fig 8.16. PXRD spectra of LH ( 2e ).

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Fig 8.17. PXRD spectra of Co(II) complex ( 3e ).

Fig 8.18. PXRD spectra of Ni(II) complex ( 4e ).

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Fig. 8.19. PXRD spectra of Cu(II) complex ( 5e ).

Fig 8.20. PXRD spectra of Mn(III) complex ( 6e ).

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Fig 8.21. PXRD spectra of Fe(III) complex ( 7e ).

Fig 8.22. PXRD spectra of Cr(III) complex ( 8e ).

8.3.4. Mass spectral studies To clarify the structure of the synthesized compounds at the molecular level, electrospray ionization (ESI) mass spectrometry was recorded using methanol as solvent. Mass-spectra of the LH ( 2e ) had a molecular ion peaks at m/z 264, that 156

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+ + corresponds to [M-BF 4] , (M = [C13 H15 ClN 3O] ) ion. The Co(II) complex ( 3e ) + exhibited molecular ion peaks ( m/z ) at 585, which was assigned to [M-2BF 4] (M= + + [(C 26 H28 CoCl 2N6O2] ) ion. The molecular ion peaks appeared at 586 ([M+2H-2BF 4] , + + + M= [(C 26 H28 NiCl 2N6O2] ) and at 588 ([M-H-2BF 4] , M= [(C 26 H28 CuCl 2N6O2] ) were assigned for Ni(II) complex ( 4e ) and Cu(II) complex ( 5e ) respectively. The mass spectra of the Mn(III) complex ( 6e ) shown a molecular ion peck at 616 which was + + due to [M+2H-2BF 4-H2O] ion where M= [C26 H28 MnCl 3N6O2] . The Fe(III) complex + (7e ) and Cr(III) complex ( 8e ) displayed pecks at 618 for [M-H-2BF 4-H2O] , M= + + + [C26 H28 FeCl 3N6O2] ion and 613 for [M-2BF 4-H2O] , M= [C26 H28 CrCl 3N6O2] ion. The mass spectra of the ligand and complexes were in good agreement with the respective structures as revealed by the elemental and other spectral analyses. The ESI-MS spectra of the ligand and complexes are shown in Figs 8.23-8.29.

Fig 8.23 . ESI-MS spectrum of LH ( 2e ).

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Fig 8.24 . ESI-MS spectrum of Co(II) complex ( 3e ).

Fig 8.25. ESI-MS spectrum of Ni(II) complex (4e).

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Fig 8.26 . ESI-MS spectrum of Cu(II) complex ( 5e )

Fig. 8.27 . ESI-MS spectrum of Mn(III) complex ( 6e ).

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Fig 8.28 . ESI-MS spectrum of Fe(III) complex ( 7e ).

Fig 8.29 . ESI-MS spectrum of Cr(III) complex ( 8e ).

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8.3.5. Electronic absorption spectral and magnetic moment studies The UV-Visible spectra of the Schiff base and its metal complexes (as shown in Fig 8.30.) were recorded at ambient temperature using methanol as solvent. The LH (2e ) exhibited three absorption bands at 336, 250 and 220 nm due to n →π*, π→π * and transitions involved with the imidazolium moiety, respectively [45, 46]. For the complexes ( 3e , 4e and 5 e), the bands that appeared below 350 nm were ligand centred transitions (n →π* and π→π *). The Co(II) complex ( 3e ) showed a shoulder at 398 nm 2 1 1 2 which was attributed to the combination of B1g → A1g and B1g → Eg transitions and supporting square planar geometry [47, 48]. The complex ( 3e ) showed magnetic moment of 2.32 B.M. due to an unpaired electron. The Ni(II) complex ( 4e ) was 1 1 diamagnetic and the band observed at around 400 nm due to A1g → B1g transition was consistent with low spin square planar geometry [49]. UV-visible spectra of Cu(II) complex ( 5e ) displayed d →π* metal -ligand charge transfer transition (MLCT) 2 2 2 2 at the region 395 nm was assigned for combination of B1g → Eg and B1g → B2g transitions in a distorted square planar geometry [50, 51]. The experimental magnetic moment value for 5e was 1.82 B.M. consistent with the presence of an unpaired electron [52]. In the UV-Visible spectra of Mn(III) complex ( 6e ) three bands at 339, 243 and 216 nm were observed. Due to its d 4 electronic structure; electronic transition 5 5 was assigned to T2g → Eg which proposed that the metal centre was effectively coordinated by ligand in octahedral environment [53, 54]. The observed magnetic moment was found 4.84 B.M. for Mn(III) complex ( 6e ). The Fe(III) complex ( 7e ), (d 5 configuration) showed bands at 343, 245 and 215 nm. The band at 343 nm, assigned 6 to the spin and parity forbidden A1g →T2g transition of Fe(III) ion in an octahedral field. The high spin octahedral Fe(III) complexes used to show very weak and spin forbidden d-d transition which didn’t appear in the spectra due to the low intensity of the d-d transition. The observed magnetic moment of 5.62 B.M. for 7e suggested high spin configuration of the metal ion with five unpaired electrons [55]. UV-visible spectrum of the Cr(III) complex( 8e ) exhibited three bands at 394, 338, 220 nm. These 4 4 4 4 4 4 bands could be attributed to A2g (F) → T2g (F), A2g (F) → T1g (F) and A2g (F) → T1g (P) transitions, respectively suggesting octahedral geometry around the Cr(III) ion [56, 52]. Again the complex 8e showed magnetic moment of 3.93 B.M. corresponding to three unpaired electrons.

161

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Fig 8.30. The UV-Vis spectra of ligand ( 2e ) and its metal complexes ( 3e to 8e ).

8.3.6. Antimicrobial activities Antimicrobial susceptibility tests were conducted to assess the efficacy of synthesized compounds. The seven synthesized compounds showed variable results (Fig 8.31 and Table 8.1). All the compounds except 6e showed positive responses. The samples showed almost similar results for gram positive and negative bacterial samples. Maximum inhibition zone was produced by the Cu(II) complex ( 5e ) in plates of Klebsiella pneumoniae while the minimum inhibition zone was produced by Bacillus cereus. Staphylococcus aureus showed maximum susceptibility for the all the samples in comparison to the other bacterial cultures. So, it was concluded that the ligand ( 2e ) along with its metal complexes ( 3e , 4e , 5e , 6e , 7e and 8e) inhibited the growth of pathogenic bacteria like Staphylococcus aureus , Bacillus cereus , Escherichia coli and Klebsiella pneumoniae.

162

Chapter VIII

Table 8.1: Antibacterial activities of the ligand (2e) and its metal complexes (3e to 8e). Minimum inhibition concentration (mm) Specimen Gram positive Gram negative E. coli K. pneumoniae B. cereus S. aureus

LH (2e) 22 18 18 25

Co(II) complex (3e) 35 21 35 36

Ni(II) complex (4e) 33 30 34 35 Cu(II) complex (5e) 28 42 20 36 Mn(III) complex (6e) ------Fe(III) complex (7e) 35 30 35 38 Cr(III) complex (8e) 32 31 24 34

Fig 8.31. MIC of the Cu(II) complex (5e) against K. pneumoniae and B. cereus .

163

Chapter VIII

8. 4. Conclusion In this work, new transition complexes of an ionic liquid-based Schiff base, 1- {2-(2-hydroxy-5-chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate were synthesized and characterized by different spectral and analytical techniques. The Schiff base ligand act as a potential bidentate ligand coordinating through the N-atom of azomethine and O-atom of phenolic group to the metal ions and thus formed 1:2 (M:L) complexes. Spectral and magnetic susceptibility data revealed that the ligand was arranged in square planner geometry in case of Co(II), Ni(II) and Cu(II) complexes although in case of Mn(III), Fe(III) and Cr(III) complexes it was oriented in octahedral geometry around the central metal ions. The antimicrobial study of the synthesized compounds was performed and metal complexes have exhibited promising activity against the tested bacteria. References [1] P.T. Anastas, M.M. Kirchhoff, T.C. Williamson, Appl. Catal. A. 221 (2001) 3. [2] R.D. Rogers, K.R. Seddon, Science. 302 (2003) 792. [3] R.A. Sheldon, Chem. Soc. Rev. 41 (2012) 1437. [4] J. Dupont, R.F. de Souza, P.A.Z. Suarez, Chem. Rev. 102 (2002) 3667. [5] K.R. Seddon, J. Chem. Technol. Biotechnol. 68 (1997) 351. [6] T. Welton, Chem. Rev. 99 (1999) 2071. [7] C.M. Gordon, Appl. Catal. A Gen. 222 (2001) 101. [8] N. Jain, A. Kumar, S. Chauhan, S.M.S. Chauhan, Tetrahedron. 61 (2005) 1015. [9] P. Wasserscheid, T. Welton, Ionic liquid in Synthesis, 2 nd ed, Wiley-VCH, Weinheim, 2008. [10] H. Zhao, S.V. Malhotra, Aldrichim. Acta. 35 (2002) 75. [11] F. Endres, T. welton, P. Wasserscheid, Ionic liquids in Synthesis, Wiley-VCH, WeinHein, pp 289-318, 2003 [12] T.L. Husum, C.T. Jorgensen, M.W. Christensen, O. Kirk, Biocatalysis Biotransform. 19 (2001) 331. [13] U. Kragl, M. Eckstein, N. Kaftzik, Curr. Opin. Biotechnol. 13 (2002) 565. [14] S. Park, R.J. Kazlauskas, Curr. Opin. Biotechnol. 14 (2003) 432. [15] R.A. Sheldon, R.M. Lau, M.J. Sorgedrager, F. van Rantwijk, K.R. Seddon, Green Chem.,4 (2002) 147.

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Concluding Remarks

The main aim of this research work presented in this thesis was to synthesize transition metal complexes from amine functionalized ionic liquid-supported Schiff bases (mainly imidazolium based), their physico-chemical characterization and exploration of their antibacterial and antimicrobial activities against some naturally available gram positive and gram negative bacteria. Chapter I deals with the general idea about ionic liquids, their fascinating characteristics and their applications in different fields. It also contains a brief literature review as a back ground for the object and application of the research work undertaken. Chapter II deals with the experimental sections giving the details of the reagents and solvents used to synthesize various ionic liquids-supported Schiff bases and their transition metal complexes as well as a brief note on the spectroscopic and analytical techniques utilized to characterize the synthesized compounds. In chapter III the synthesis, characterization and antibacterial activities of the Mn(II) and Co(II) complexes of an ionic liquid-supported Schiff base, [1-{2-(2- hydroxybenzylideneamino)ethyl}-3-methyl-1Himidazolium] bromide were discussed. It was found that the Schiff base acted as a bidentate ligand and formed tetrahedral 1:2 (M:L) complexes with Mn 2+ and Co 2+ ions. The Schiff base and its complexes were hygroscopic in nature. The synthesized compounds were tested for their antibacterial activities against two commonly known bacteria, viz., Escherichia coli and Bacillus subtilis . The observed minimum inhibition (MIC) concentrations revealed that the synthesized complexes have slight antibacterial activities against the bacteria Escherichia coli and Bacillus subtilis . In chapter IV the investigation on the Mn(II), Co(II) and Cu(II) complexes derived from a Schiff base, [1-{2-(2- hydroxybenzylideneamino)ethyl}-3-methyl imidazolium hexafluorophosphate was described. The complexes were formed in 1:2 (M:L) ratio as confirmed by the various analytical and spectral analyses. The complexes are soluble in N,N- dimethylformamide, dimethylsulphoxide and methanol but immiscible in water. The ligand and synthesized complexes were screened against the bacteria Bacillus subtilis and Escherichia coli. The Cu(II) complex exhibited no antibacterial activities where as the Mn(II) and Co(II) complexes showed minimum activities against the selected

167

Concluding Remarks bacteria. In chapter V the physico-chemical characterization and antibacterial activities of the Co(II), Ni(II) and Cu(II) complexes derived from an ionic liquid- supported Schiff base, 1-{2-(2-hydroxy-5-nitrobenzylideneamino)ethyl}-3- ethylimidazolium tetrafluoroborate were described. It was observed that the Schiff base has square planner geometry around the metal ions in the metal complexes. The antibacterial studies of the synthesized compounds were performed and the metal complexes exhibited significant activities against the selected gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Enterobacter aerogenes ) and gram positive bacteria ( Staphylococcus aureus and Bacillus cereus ). The observation suggested that the chelation might have facilitated the capability of the complexes to penetrate bacterial cell membrane, i.e ., such a chelation could have enhanced the lipophilic property of the corresponding metal ions that favours permeation through the lipid layer of cell membrane. Such activities for both the complexes and ligand were found to enhance as their concentration in the assay analyses increased due to enhanced degree of inhibition against the respective bacteria. In chapter VI the syntheses and physico-chemical characterization of Co(II), Ni(II) and Cu(II) complexes of the Schiff base, 1-{2-[(2-hydroxy-5- bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate were described. It was found that the bidentate ligand coordinates to the metal ions through the azomethine nitrogen (-HC=N-) and phenolic O-atoms and formed square planar complexes. The synthesized complexes showed reasonable antibacterial activities against the selected four gram negative bacteria ( E. coli, P. aeruginosa, P. vulgaris and E. aerogenes ) and two gram positive bacteria ( S. aureus and B. cereus ). From the inhibitory zones, it is clear that the Schiff base is most effective against the five organisms except E. aerogenes . The Co(II) complex is most effective against P. vulgaris and E. aerogens . The Ni(II) complex was observed to be very active against E. coli, S. aereus, P. aeruginosa and E. aerogenes . It was found that the Cu(II) complex is most active against E. coli, S. aereus, B. Cereus, P. aeruginosa and P. Vulgaris. In chapter VII, an ionic liquid-supported Schiff base, 1-{2-(2-hydroxy-5- bromobenzylamine)ethyl}-3-ethylimidazolium tetrafluoroborate and its Fe(III) and 168

Concluding Remarks

Cr(III) complexes were synthesized and characterized by different spectroscopic and analytical techniques. These data suggested distorted octahedral geometries for both the metal complexes. The Schiff base coordinates to the metal ions through the azomethine nitrogen (-HC=N-) and phenolic O-atom and thus formed 1:2 (M:L) complexes with Fe(III) and Cr(III) ions. The synthesized complexes along with the ligand were tested for their in vitro antibacterial activities. A detectable antibacterial activity was observed for the Cr(III) complex against the bacteria Escherichia coli and Staphylococcus aureus. Chapter VIII described the synthesis, physico-chemical characterization and potential biological applications of some transition metal complexes of the Schiff base, 1-{2-(2-hydroxy-5-chloro-benzylideneamino)ethyl}-3- methylimidazolium tetrafluoroborate. Interestingly the ligand was observed to form square planner complexes with Co(II), Ni(II) and Cu(II) ions but it formed octahedral complexes with Mn(III), Fe(III) and Cr(III) ions. Overnight broth culture grown for the four bacterial strains (two gram positive bacteria, viz ., Staphylococcus aureus and Bacillus cereus and two gram negative bacteria, viz ., Escherichia coli and Klebsiella pneumoniae ) revealed that all the synthesized compounds except the Mn(III) complex have positive responses. Maximum inhibition zone was produced by the Cu(II) complex in plates of Klebsiella pneumoniae and the minimum inhibition zone was produced in case of Bacillus cereus. Anyway, the most of the synthesized ionic liquid-supported Schiff bases and their transition metal complexes were air and moisture stable and biologically active. There are so many scopes to alter the cation or anion part and turn them for a specific applications but the major problem in dealing with their synthesis is poor yield and cumbersome purification process. Another concern regarding these ionic liquids or ionic liquid-supported Schiff bases may be environment issues, i.e. , their toxicity and biodegradibilty. However, the lucrative aspect of the so-called ionic liquid-supported Schiff bases and their transition metal complexes is that they are often suitable materials for various catalyses and a variety of pharmaceutical applications. Therefore, further investigation on their easy way of preparation, purification and potential applications as well as their toxicity and bio-degradability is required and some works targeting these issues are underway in our laboratory.

169

APPENDIX I

List of Publications

[1] Physico-chemical characterization and biological studies of newly synthesized metal complexes of an Ionic liquid-supported Schiff base: 1-{2-[(2-hydroxy-5- bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate. J. Chem. Sci. 130 (2018) 1-9, DOI: org/10.1007/s12039-017-1409-9. [2] Synthesis, characterization and antibacterial studies of Mn(II) and Co(II) complexes of an ionic liquid tagged Schiff base. J. Serb. Chem. Soc. 81 (2016) 1151–1159. DOI: 10.2298/JSC160425065S. [3] Cu(II) complexes of an ionic liquid-based Schiff base [1-{2-(2-hydroxy

benzylidene amino) ethyl}-3-methylimidazolium]PF 6: Synthesis, characterization and biological activities. J. Serb. Chem. Soc. 80 (2015) 35-43. DOI: 10.2298/JSC140201078S.

170 APPENDIX II

List of Communicated Articles

[4] New Co(II) and Cu(II) complexes derived from an imidazolium ionic liquid- based Schiff base : Synthesis, Physico chemical characterization and exploration of Antibacterial activities, Communicated .

[5] Synthesis, Physico-chemical characterization and potential biological applications of Transition metal complexes obtained from an ionic liquid- supported Schiff base ligand: 1-{2-(2-hydroxy-5-chlorobenzylideneamino)ethyl}-3-methylimidazolium tetrafluoroborate, Communicated . [6] Synthesis, Physico-chemical Characterization and Antibacterial studies of Fe(III) and Cr(III) complexes with an Ionic Liquid-supported Schiff base ligand, Communicated .

171 APPENDIX III

List of Other Publications

[1] Thermo physical properties of binary mixtures of N, N- dimethylformamide with three cyclic esters. J. Serb. Chem. Soc. 78 (9) 1443-1460 (2013). [2] Sustainable Development and Green Chemistry: A chapter in a book, 2012, Resource Management: Human and Natural, Perspective on North- East Region. Published By Readers Service, ISBN 978-81-87891-47-5. [3] Plastic Pollution in Darjeeling District: A Review. A Chapter in a book, 2014, A Comprehensive District Profile of Darjeeling. Published By N.L. Publishers, ISBN 978-81-86860-97-7

172 APPENDIX IV

Seminar, Symposium & Convention Attended

‹ Science Academies’ Lecture Workshop on Recent Trends in Chemistry, organized by Department of Chemistry, University of North Bengal, November 11-12, 2011. ‹ UGC Sponsored National Seminar, organized by Kalimpong College, Kalimpong, Darjeeling, March 24-25 th ’ 2012. ‹ National Seminar on Frontiers in Chemistry, organized by Department of Chemistry, University of North Bengal, 28 th february’ 2013. ‹ National Seminar on Frontiers in Chemistry, organized by Department of Chemistry, University of North Bengal, 11-12 th March’ 2014. ‹ One day seminar on Chemistry organized by The Chemical Research Society of India NBU Local Chapter in collaboration with Department of Chemistry, University of North Bengal, September 12, 2014. ‹ Science Academies’ Lecture Workshop on “Spectroscopy of Emerging Materials” organized by Department of Chemistry, University of North Bengal, November 26-27’ 2014. ‹ One day seminar on “Recent Trends on Chemistry and Biology Interface” organized by The Chemical Research Society of India NBU Local Chapter in collaboration with Department of Chemistry, University of North Bengal, August 28, 2015. ‹ Science Academies’ Lecture Workshop on “Recent Developments on the Theoretical and experimental aspects of advanced materials” organized by Department of Chemistry, University of North Bengal, September 18-19, 2015. ‹ UGC Sponsored National Seminar, organized by Department of Botany & Zoology, Kalimpong College, Kalimpong, Darjeeling, 3-4th October’ 2015. ‹ 19TH CRSI NATIONAL SYMPOSIUM IN CHEMISTRY, ORGANIZED BY DEPARTMENT OF CHEMISTRY, UNIVERSITY OF NORTH BENGAL.14-16 th July’2016.

173

‹ Frontiers in Chemistry-2017, Organized by department of Chemistry, NBU. 20-21 st February’ 2017 ‹ Chemical Science Horizon, Organized by Department of Chemistry, Raiganj University, Raiganj, W.B. 16 th March’ 2017. ‹ INTERNATIONAL CONFERENCE On Contemporary Issues in Integrating Climate-The Emerging Area of Agriculture, Horticulture, Biodiversity, Forestry; Engineering Technology, Applied Science and Business Management for Sustainable Development (AGROTECH-2017) Organized by Himalayan Scientific Society for Fundamental and Applied Research. 11-12 th May’ 2017. ‹ Science Academies’ Lecture Workshop on New Light in the Horizon of Chemistry. Organized by Department of Chemistry, Kaliyaganj College, Uttar Dinajpur, West Bengal. 5-6th January’ 2018. ‹ In ternational Seminar on “Changing World, Changing Scenario: Challenges and Developments in Contemporary times” Organized by Islampur College. Uttar Dinajpur, West Bengal. 27-28 th March’ 2018.

174

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186 INDEX Page No. A AAS 31 1 alkylimidazole 3 Alkylammonium ion 2 Alkylphosphonium ion 2 Ampicilin 64 72, 135 Antibacterial activity 36, 64, 80, 101, 118, 135, 162 Azomethine group 57, 72, 90 , 111, 129, 148 B Bacillus cereus 40, 90, 102, 119, 162 Bacillus subtilis 40, 64, 80 Bis(trifluoromethylsulfonyl)imide 2 Bragg diffraction angle 97, 153 2-bromoethyl amine hydrobromide 28, 44, 50 5-bromo-2-hydroxy benzaldehyde 28, 108 Broth micro dilution method 147 C Chromoim chloride 29, 127 Cobalt acetate 28, 55 Cupper acetate 28 5-chloro-2-hydroxy benzaldehyde 28, 140 13C -NMR 63, 78, 97, 117, 152 D Disc diffusion method 64, 72, 90, 110 Debye Scherer’s equation 97, 153 E Electronic absorption spectra 63, 79, 117, 133, 161 Enterobactor aerogenes 38, 90, 101, 119 Contd…

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Page No. Escherichia coli 37, 64, 80, 90, 102, 135, 162 Ethyl ammonium nitrate 13

1-ethyl imidazole 28, 46 F FILs 4-6 Ferric chloride 29, 127 Functionlized cations 4-5 Functionlized anions 6 FWHM 97, 153 Fourier transform infrared spectrometer 33 FT-IR spectra 58, 72, 91 ,110, 130, 141, 148 FT-NMR spectrometer 34 G Gram negative bacteria 37 Gram positive bacteria 40 H Hexafluorophosphate ion 2 1H NMR spectra 62, 78. 96, 116, 132, 145 2-hydroxy-5-nitro benzaldehyde 28, 88 Hypsochromic shift 63, 79 I Imidazolium ion 2 Ionic material 86 K Keto-enol tautomerism 10, Klebsiella pneumoniae 39, 147, 162 M Manganese acetate 29, 55 Magnetic susceptibility 30 Magnetic moment 79, 100, 117, 133, 161 Contd…

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Page No. Mass spectra 59, 75, 93, 113, 131, 157 Mass spectrometer 35 Mc. Farland 101, 118 Methyl sulfonate ion 2 Michael Reaction 14, 15 Metathesis reaction 4 1-methyl imidazole 28, 41, 44, 50 Minimum inhibition concentration 64, 81, 135, 163 Mono functionalized cations 5 Molar conductance 62, 100, 117, 132 N NCCLs 110, 134 Nickel acetate 28 P Paper disc method 36, 147 Potassuim hexa fluorophosphate 28, 45 Proteus vulgaris 38, 90, 119 Pseudomonas aeruginosa 38, 102, 119 PXRD 32 , 97, 153 S Salicylaldehyde 10, 28, 55, 70 Schiff base 7-11 SEM 128, 136-140 Sodium tetrafluoroborate 28, 47 Specific conductance 62, 100, 117, 132 Staphylococus aureus 40, 90, 101, 124, 135, 162 T Tautomerism 10 Thermal analysis 134 Thermal analyzer 35 Contd…

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Page No. TEM 3 Tetrafluoroborate ion 2 Thin layer chromatography 32, 55, 88, 141 TSIL 14, 15 U UV-visible spectrophotometer 33 V VOC 1-2

190

SANJOY SAHAa,∗, GOUTAM BASAKb and BISWAJIT SINHAc aDepartment of Chemistry, Kalimpong College, Kalimpong, West Bengal 734 301, India bDepartment of Microbiology, Raiganj University, Raiganj, West Bengal 733 134, India cDepartment of Chemistry, University of North Bengal, Darjeeling, West Bengal 734 013, India E-mail: [email protected]

MS received 31 August 2017; revised 22 November 2017; accepted 22 November 2017

Abstract. Co(II), Ni(II) and Cu(II) complexes of an ionic liquid-supported Schiff base 1-{2-[(2-hydroxy-5- bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetraﬂuoroborate were synthesized and characterized by various analytical and spectroscopic methods such as elemental analysis, UV-Visible, FT-IR,1H NMR, ESI MS, molar conductance and magnetic susceptibility measurements. Based on the spectral studies, tetra coordinated geometry was proposed for the complexes and molar conductance of the complexes revealed their electrolytic nature. The synthesized Schiff base and its complexes were evaluated for in vitro antibacterial activities against Gram positive and Gram negative bacteria. The complexes along with the Schiff base showed very signiﬁcant biological activity against the tested bacteria.

Keywords. Ionic liquid-supported Schiff base; Co (II)complex; Ni (II)complex; Cu (II)complex; antibacterial activity.

1. Introduction the field of inorganic and material chemistry. 8,9 The concept of functionalized ionic liquid (FILs), by introducing Ionic liquids (ILs) are organic salts which have low melt- additional a functional group as a part of cation or anion, ing points below the boiling point of water and are stable has presently become a subject of interest. 10Ð15 There ◦ in a liquid state at 100 C, even at room temperature. is a huge possibility of chemical structure modifica- They can exhibit numerous desirable properties such as tions through the incorporation of specific functionality. negligible vapor pressure, 1 ability to dissolve various Such FILs are able to interact with a metal centre substrates, high electrical conductivity 2 and thermal sta- and contribute to enhanced stability of metal salts. 16 bility. 3Ð5 ILs are touted as alternatives to volatile organic Metal-containing ILs are considered as promising new solvents (VOC) in various organic transformations. Due materials that combine the feature of ILs with additional to low toxicity and biodegradability, they have been intrinsic magnetic, catalytic and spectroscopic proper- termed as green solvents. 6 An unusual feature of ILs ties depending on the incorporated metal ion. 17 is the tenability of their physical and chemical proper- Schiff bases, usually formed by the condensation of a ties by variation of cations and anions. Usually, large primary amine with an aldehyde are one of the most organic cations and smaller anions are designed to carry prevalent ligands in coordination chemistry. 18 Schiff on required functions. 7 Although most of the works on bases containing hetero-atoms such as nitrogen, oxygen ILs highlight their use as reaction media in organic syn- and sulphur are of special interest due to their different thesis, these liquids are gradually drawing attention in ways of bonding with transition metal ions and unusual configuration. 19 They have been reported to exhibit a variety of biological actions due to the presence of *For correspondence azomethine linkage, which is responsible for different Electronic supplementary material: The online version of this article (https:// doi.org/ 10.1007/ s12039-017-1409-9) contains supplementary material, which is available to authorized users. 9 Page 2 of 9 J. Chem. Sci. (2018) 130:9 types of antibacterial, herbicidal and antifungal activ- were determined by the open capillary method. Antibacte- ities. 20,21 Transition metal complexes of Schiff bases rial activities (in vitro) of the synthesized compounds were carrying nitrogen and other donor sites have a variety tested by disc diffusion method. All the bacteria strains were of applications including biological, medicinal analyt- procured from MTCC, Chandigarh, and were cultured at the ical in addition to their vital role in organic synthesis Department of Microbiology, Raiganj University, Raiganj, and catalysis. 22Ð26 We reported in previous articles the West Bengal, India. synthesis, characterization and biological influence of 2.3 Synthesis of 1-(2-aminoethyl)-3-ethylimidazolium Cu(II), Mn(II) and Co(II) complexes of analogous ionic tetrafluoroborate, [2-aeeim]B F (1) liquid-supported Schiff bases. 27,28 This paper reports 4 on the synthesis of transition metal Co(II), Ni(II) and The amino functionalized ionic liquid [2-aeeim]BF4 was syn- Cu(II) complexes of an ionic liquid-supported Schiff thesized by following a literature procedure. 29 Yield: 79%; base and their characterization using spectroscopic, ana- C7H14F4N3B : Anal. Found: C, 37.02; H, 6.12; N, 18.38% lytical and magnetic data. Furthermore, the applications Calc.: C, 37.04; H, 6.22; N, 18.51%. IR (KBr, υ/cm−1): of the Schiff base and its complexes as potential antibac- (υO−H) 3447, 3086, 2896, 1626, 1452, (υBF4) 1084. ESI-MS + + terial agents have also been demonstrated. (m/z): Calc.: 140: Found: 140 ([M-BF4] ,M=[C7H14N3] ). 1 H NMR (400 MHz, D2O, TMS): δ3.63 (2H, m, NH2-CH2), 4.16 (3H, s, CH3),4.49(1H,t,N-CH2),4.56(1H,t,N-CH2), 7.40 (1H, s, NCH), 7.50 (1H, s, NCH), 8.61 (2H, s, NH2), 2. Experimental 13 8.87 (1H, s, N(H)CN); C NMR (400 MHz, D2O, TMSO) δ: 135.95, 123, 122.50, 50.81, 45.54, 45.3, 14.57. 2.1 Materials 2.4 Synthesis of imidazolium ionic liquid-tagged All the reagents used were of analytical grade and used with- Schiff base, LH (2) out further purification. 1-ethylimidazole, 2-bromoethylamine hydrobromide and sodium tetrafluoroborate were procured The ionic liquid-tagged Schiff base (LH) was synthesized by from Sigma Aldrich, Germany. 5-bromo-2-hydroxy ben- a slight modification of a literature procedure. 30 A mixture zaldehyde, Co(II), Ni(II) and Cu(II) acetates and all other of 5-bromo-2-hydroxy benzaldehyde (2.01 g, 10 mmol) and chemicals were used as received from SD Fine Chemicals, [2-aeeim]BF (2.27 g, 10 mmol) in methanol was stirred at India. The solvents methanol, petroleum ether, chloroform, 4 room temperature for 12 h. After completion of the reaction, DMF and DMSO were used after purification by the standard as indicated by TLC, the reaction mixture was diluted with methods described in the literature. EtOH. The precipitate was filtered, washed with cold ethanol and dried to afford the expected ligand as a light yellow 2.2 Instrumentation solid.

◦ IR spectra were recorded in KBr pellets with a Perkin- 2.4a LH(2): M.p.: 98Ð100 C; Yield: 65Ð70%; C14H17 Elmer Spectrum FT-IR spectrometer (RX-1) operating in the N3OBBrF4Anal. Found: C, 40.91; H, 4.11; N, 10.21%. Calc.: −1 1 −1 region 4000 to 400 cm . H-NMR was recorded at room C, 41.01; H, 4.18; N, 10.25(%). IR (KBr, υ /cm ):(υO−H) temperature on an FT-NMR (Bruker Avance-II 400 MHz) 3449, (υCH=N) 1673, (υC−O) 1276, (υBF4) 1114. UV-Vis spectrometer using DMSO-d6 and D2O as solvents. Chemi- (Methanol) λmax/nm: 218, 250, 336. ESI-MS (m/z): Calc. + + 1 cal shifts are mentioned in ppm downfield of internal standard 323: Found: 323 ([M-BF4] ,M=[C14H17N3O] ). HNMR: tetramethylsilane (TMS). Elemental microanalyses (C, H and (400 MHz, DMSO-d6,TMS):δ 3.32 (3H, s, CH3),3.82(1H, N) were conducted by using PerkinÐElmer (Model 240C) ana- t, N-CH2),3.99(1H,t,N-CH2),4.52(1H,t,N-CH2), 6.91Ð lyzer. Metal content was determined with the aid of AAS 6.85 (3H, m, Ar-H), 7.33 (1H, s, NCH), 7.42 (1H, s, NCH), (Varian, SpectrAA 50B) by using standard metal solutions 8.50 (1H, s, N=CH), 7.73 (1H, s, N(H)CN), 9.10 (1H, s, OH). 13 from Sigma-Aldrich, Germany. Mass spectra were recorded C NMR (400 MHz, DMSO-d6,TMSO):δ 137.31, 135.59, on a JMS-T100LC spectrometer. The purity of the prepared 123.76, 123.09, 122.41, 122.25, 119.63, 53.91, 48.52, 48.14, compounds was confirmed by thin layer chromatography 44.99, 43.71, 41.15, 35.90. (TLC) on silica gel plates and the plates were visualized with UV-light and iodine as and when required. The UV-Visible 2.5 Synthesis of metal complexes(3, 4 and 5) spectra were recorded in methanol with a JascoV-530 double beam Spectrophotometer at ambient temperature. Molar To a solution of ligand, LH (0.410 g, 1 mmol), in EtOH (20 conductances were measured at (298.15 ± 0.01) K with a mL) solution of ethanolic metal acetate salt Co(II), Ni(II) and Systronic conductivity meter, TDS-308. Magnetic suscepti- Cu(II)), viz., (0.5 mmol) was added and the reaction mix- bilities were measured at room temperature using a magnetic ture was refluxed for 4 h until the starting materials were susceptibility balance (Magway MSB Mk1, Sherwood Scien- completely consumed as monitored by TLC. On completion tific Ltd). The melting point of the ligand and its complexes of the reaction, solvents were evaporated and the reaction J. Chem. Sci. (2018) 130:9 Page 3 of 9 9

Scheme 1. Synthesis of the ionic liquid-tagged Schiff base, 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3- ethylimidazolium tetrafluoroborate (2), and M(II) complexes (3, 4 and 5)fromLH(2). mixture was cooled to room temperature. The precipitate 2.6 Antibacterial assay was collected by filtration, washed successively with cold ethanol (3×10 mL). Finally, it was dried in vacuum desic- Antibacterial activities of the synthesized compounds were cators to obtain the solid product. The complexes are soluble tested in vitro against the four Gram negative bacteria (E. coli, in N, N−dimethylformamide, dimethylsulphoxide, acetoni- P. aeruginosa, P. vulgaris and E. aerogenes) and two Gram trile, methanol and water. A schematic representation of the positive bacteria (S. aureus and B. cereus) strains using agar synthesis is shown in Scheme 1. disc diffusion method 31,32 by NCCLS (National Committee for Clinical Laboratory Standards, 1997, India). The nutrient agar (Hi-Media Laboratories Limited, Mumbai, India) was ◦ 2.5a Co(II) complex (4): Brown solid; M.p.: 128Ð autoclaved at 121 C and 1 atm for 15Ð20 min. The ster- ◦ − ◦ μ 130 C; C28H32CoB2Br2F8N6O2: Anal. Found: C, 38.16; H, ile nutrient media was kept at 45 50 C, after that 100 L 3.53; N, 9.32, Co, 6.42%. Calc.(%) for C, 38.35; H, 3.68; of bacterial suspension containing 108 colony-forming units −1 N, 9.58; Co, 6.72%. IR (KBr, υ /cm ):(υO−H/H2O) 3442, (CFU)/mL were mixed with sterile liquid nutrient agar and (υCH=N) 1629, (υC-O ) 1316, (υBF4) 1019, (υBr) 713, (υM-O) poured into the sterile Petri dishes. Upon solidification of the 633, (υM-N) 523. UV-Vis (Methanol) λmax/nm: 220, 338, media, filter disc (5 mm diameter) was individually soaked + μ 394. ESI-MS (m/z): Calc. 701: Found: 701 ([M-BF4] ,M= with different concentration (10, 20, 30, 40 and 50 g/mL) of + [C28H32CoBr2N6O2] ). each extract and placed on the nutrient agar media plates. The different concentrations were made by adding with DMSO. The plates were incubated for 24 h at 37 ◦C. The diameter 2.5b Ni(II) complex (5): Light green solid; M.p. 140Ð of the zone of inhibition (including disc diameter of 5 mm) ◦ 142 C; C28H32NiB2Br2F8N6O2: Anal. Found: C, 38.11; H, was measured. Each experiment was performed three times 3.50; N, 9.37, Ni, 6.33%. Calc.: C, 38.36; H, 3.68; N, 9.58; to minimize the error and the mean values were accepted. −1 Ni, 6.69%. IR (KBr, υ /cm ):(υO−H/H2O) 3437, (υCH=N) 1627, (υC−O) 1314, (υBF4) 1018, (υBr) 715, (υM−O) 634, υ ) ( M−N 535. UV-Vis (Methanol) λmax/nm: 219, 340, 400. 3. Results and Discussion ESI-MS (m/z): Calc. 700: Found: 702 ([M+2]-BF4,M= [ +) C28H32NiBr2N6O2] . All the isolated compounds were stable at room temperature to be characterized by different analytical and spectroscopic methods. 2.5c Cu(II) complex (6): Dark green solid; M.p. 147Ð ◦ 149 C; C28H32CuB2Br2F8N6O2: Anal. Found: C, 38.07; H, 3.49; N, 9.31, Cu, 6.99%. Calc.: C, 38.15; H, 3.66; N, 3.1 IR spectral studies −1 9.53; Cu, 7.21%. IR (KBr, υ /cm ):(υO−H/H2O) 3448, (υCH=N) 1625, (υC−O) 1317, (υBF4) 1014, (υBr) 717, (υM−O) The assignments of the IR bands of the synthesized 648, (υM−N) 559. UV-Vis (Methanol) λmax/nm: 222, 342, Co(II), Ni(II) and Cu(II) complexes have been made + 396. ESI-MS (m/z): Calc. 705: Found: 705 ([M-BF4] ,M= by comparing with the bands of ligand (LH) to deter- + [C28H32CuBr2N6O2] ). mine the coordination sites involved in chelation. IR 9 Page 4 of 9 J. Chem. Sci. (2018) 130:9

Figure 1. IR spectrum of: (A) 1-{2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3-ethylimidazolium tetrafluoroborate (2); (B) Co(II) complex (3); (C) Ni(II) complex and (4) and (D) Cu(II) complex (5). J. Chem. Sci. (2018) 130:9 Page 5 of 9 9 spectra of the ligand, LH (2) and its metal complexes agreement with the respective structures as revealed by (3 to 5) are given in Figure 1. Only the distinct and the elemental and other spectral analyses. characteristic peaks have been discussed. IR spectra of the ligand exhibited a strong broad absorption band at 3.3 1H and 13C-NMR spectral studies 3450Ð3236 cm−1; this band was assigned to the hydrogen bonded -OH of the phenolic group with HÐC(=N) 1H-NMR and 13C-NMR spectra of ligand were recorded 33,34 group of the ligand (OH…N=C). All the com- in DMSO-d6 (Figures S3 and S4 in Supplementary plexes showed broad diffuse band at 3437−3448cm−1 Information). 1H-NMR of the ligand showed singlet which may be attributed to the presence of the coor- at 8.50 ppm is assignable to proton of the azomethine dinated/solvated water or ethanol molecules. However, group (-CH=N-) presumably due to the effect of the these bands appear stronger compare to that of the ligand ortho-hydroxyl group in the aromatic ring. A singlet at due to the moisture content of the ligand subject to the 9.10 ppm can tentatively be attributed to hydroxyl pro- intrinsic nature of the anion tetrafluoroborate. 35Ð37 The ton. The Schiff base displayed downfield shift of the band for phenolic C-O of free ligand was observed at ÐOH proton is due to intermolecular (O-H...N) hydro- 1276cm−1. Upon complexation, this band was shifted to gen bond. 44 13C-NMR spectra of ligand exhibited peaks higher wave number 1314−1317cm−1 for all the com- at δ 137.31 and 135.59 presumably due to the phenolic plexes. This fact suggests the involvements of phenolic (C-O) and imino (-CH=N) carbon atoms (due to keto- C-O in the coordination process. 38 This interpretation imine tautomerism). The chemical shifts of the aromatic is further confirmed by the appearance of M-O band carbons appeared at δ 123.76, 123.09, 122.41, 122.25 at 633−638cm−1 in the spectra of the metal com- and 119.53. (1H-NMR and 13C-NMR spectra are given plexes. The intense band at 1673cm−1that corresponds in Figures S3 and Figure S4, Supplementary Informa- to azomethine group (-C=N) in the free ligand is shifted tion). to the lower frequencies in the range 1625−1629cm−1 in case of the metal complexes, indicating the partici- 3.4 Molar conductance measurements pation of azomethine group (-C=N) in the coordination 39 sphere. This is further emphasized by the appearance The molar conductance of the complexes (Λm ) were of a new weak to medium intensity absorption band in measured by using the relation Λm = 1000 × κ/c, the region 523−559cm−1that may be attributed to M- where c and κ stands for the molar concentration of the N stretching vibration for the metal complexes. 40 The metal complexes and specific conductance, respectively. bands in the range of 1014−1019cm−1for the spectra The complexes (1 × 10−3 M) were dissolved in N, N- of metal complexes are assigned for B-F stretching fre- dimethylformamide and their molar conductivities were quency. measured at (298.15±0.01) K. The conductance values were in the range of 134, 131 and 130 S cm−1mol−1, respectively, for the metal complexes (3 to 5), indicat- 3.2 Mass spectral studies ing their 1:2 (M:L) electrolytic behaviour.

To get information regarding the structure of the syn- 3.5 Electronic absorption spectral and magnetic thesized compounds at the molecular level, electro- moment studies spray ionization (ESI) mass spectrometry was performed using methanol as solvent. ESI-MS spectrum UV-Visible spectra of the ligand and the metal com- of the compound, [2-aeeim]BF4 showed a peak at 140 plexes (Figure 2) were recorded at ambient temperature + + + 41 ([M-BF4] , which corresponds to M , [M=C7H14N3] . using methanol as solvent. The electronic spectrum of + The ligand (LH) exhibited a peak (m/z) at 323 [M-BF4] , free Schiff base exhibited three absorption bands at 336, + 42 ∗ ∗ which can be assigned to [M= C14H17N3O] . The 250 and 218 nm due to n → π , π → π and transitions Co(II) complex (3) displayed a peak (m/z) at 701.49 involved with the imidazolium moiety, respectively. 45,46 + which corresponds to the [M-BF4] ion. A peak (m/z) For the complexes, the bands that appeared below 350 at 701.62 in the ESI-MS spectrum of Ni(II) complex (4) nm were ligand centred transitions (n → π∗ and + ∗ is assigned to the [M+H-BF4] ion. In the ESI-MS spec- π → π ). The Co(II) complex (3) displayed a band at trum, the Cu(II) complex (5) exhibited a peak (m/z) at 394 nm which could be assigned to the combination of + 43 2 1 1 2 705.74 which is assigned to the [M-BF4] ion. (The B1g → A1g and B1g → Eg transitions and supporting ESI-MS spectra of the complexes and ligand are given in square planar geometry. 47,48 The complex (3)showsthe Figures S1 and S2 in Supplementary Information). The magnetic moment of 2.30 BM due to one unpaired elec- mass spectra of the ligand and complexes were in good tron. The Ni(II) complex (4) was diamagnetic and the 9 Page 6 of 9 J. Chem. Sci. (2018) 130:9

Figure 2. UV-visible spectra in methanol (concentration of the solutions 1 × 10−4 M): (A) the ligand(2); (B) Co(II)complex(3); (C) Ni(II)complex(4) and (D) Cu(II) complex(5).

Figure 3. Inhibition zones for the ligand (2), Co(II) complex (3), Ni(II) complex (4) and Cu(II) complex (5). J. Chem. Sci. (2018) 130:9 Page 7 of 9 9

1 1 band around 400 nm due to A1g → B1g transition is showed most effective activity effective activity than the consistent with low spin square planar geometry. 49 The other samples. UV-visible spectra of Cu(II) complex (5) showing d → π∗ metal-ligand charge transfer transition (MLCT) in Supplementary Information (SI) the region 396 nm had been assigned to the combination Experimental biological assays data, ESI-MS and NMR 2 →2 2 →2 of B1g Eg and B1g B2g transitions in a distorted spectral data for the ligand and complexes are given as Sup- square-planar environment. 50,51 The observed magnetic plementary Information, available at www.ias.ac.in/chemsci. moment for Cu(II) complex (5) was 1.82 B.M. consistent with the presence of a single unpaired electron. 52 Acknowledgements The authors are grateful to the SAIF, NEHU, Guwahati, India 3.6 Antibacterial activities for 1HNMR,13C NMR, ESI-MS and elemental analysis.

Minimum inhibitory concentration was measured by Broth Micron dilution susceptibility method. Serial dilu- References tions of sample solutions were made in nutrient broth medium. Then 1 mL of standard (0.5 McFarland) bacte- 1. Earle M J, Esperanc J M S S, Gilea M A, Lopes J N ria suspension was inoculated into each of these tubes. C, Rebelo L P N, Magee J, Seddon K R and Widegren J A 2006 The distillation and volatility of ionic liquids A similar nutrient broth tube without sample was also Nature 439 831 inoculated and used as a control. The tubes were kept 2. Sakaebe H and Matsumoto H 2003 N-Methyl-N- at 37◦C for 24 h. The lowest concentration of sample propylpiperidinium bis(trifluoromethane sulfonyl)imide which inhibited bacterial growth was considered as min- (PP13ÐTFSI) Ð novel electrolyte base for Li battery Elec- imum inhibitory concentration. Final confirmation was trochem. Commun. 5 594 3. Rogers R D and Seddon K R 2003 Ionic LiquidsÐ done by streaking on nutrient agar medium. The samples Solvents of the Future? Science 302 792 under study have shown promising result against all the 4. Sheldon R 2005 Green solvents for sustainable organic bacterial strains (Table S1 in Supplementary Informa- synthesis: state of the art Green Chem. 7 267 tion). From the inhibitory values, it is clear that the Schiff 5. Wasserscheid P and Keim W 2000 Ionic Liquids—New based ligand is most effective against five organisms “Solutions” for Transition Metal Catalysis Angew. Chem. (MIC 10 μg/mL) except E. aerogenes. Co(II) complex Int. Ed. 39 3773 6. Anastas P T and Warner J C 1998 In Green Chemistry- (3) is most effective against P. vulgaris and E. aero- Theory and Practice (New York: Oxford University gens. Ni(II) complex (4) is observed very active against Press Inc.) E. coli, S. aereus, P.aeruginosa and E. aerogenes (MIC 7. Visser A E, Swatloski R P, Reichert W M, Mayton R, 10 μg/mL). It is seen that Cu(II) complex (5)ismost Sheff S, Wierzbicki A, Davis Jr. J H and Rogers R D 2001 effective among the others samples due to their MIC Task-specific ionic liquids for the extraction of metal ions μ from aqueous solutions Chem. Chem. Commun. 1 135Ð value of 20 g/mL against E. coli, S. aereus, B. cereus 136 and 30 μg/mL against P. aeruginosa and P. vulgaris. 8. (a) Zhou Y and Antonietti M 2003 Preparation of Highly The results are shown in Figure 3. Ordered Monolithic Super-Microporous Lamellar Sil- ica with a Room-Temperature Ionic Liquid as Template via the Nanocasting Technique Adv. Mater. 15 1452; (b) Taubert A and Li Z 2007 Inorganic materials from ionic 4. Conclusions liquids Dalton Trans. 7 723 9. (a) Endres F, Bukowski M, Hempelmann R and Natter In this research, the preparation and physico-chemical H 2003 Electrodeposition of nanocrystalline metals and characterization of new Co(II), Ni(II) and Cu(II) com- alloys from ionic liquids Angew. Chem. 115 3550; (b) plexes bearing an ionic liquid-supported Schiff base 1- Abbott A P, Capper G, Swain B G and Wheeler D A {2-[(2-hydroxy-5-bromobenzylidene)amino]ethyl}-3- 2005 Electropolishing of stainless steel in an ionic liquid Trans. Inst. Met. Finish. 83 51 ethylimidazolium tetrafluoroborate as ligand, have been 10. Miao W and Chan T H 2006 Ionic-liquid-supported syn- reported. The Schiff base and metal complexes were thesis: a novel liquid-phase strategy for organic synthesis characterized by spectral and analytical methods. The Acc. Chem. Res. 39 897 spectral and magnetic susceptibility measurements sug- 11. Kamal A and Chouhan G 2005 A task-specific ionic liq- gested that the bidentate ligand coordinates to the central uid [bmim]scn for the conversion of alkyl halides to alkyl metal ion through the azomethine nitrogen and phenolic thiocyanates at room temperature Tetrahedron Lett. 46 1489 oxygen atoms, yielding square planar complexes. The 12. Lee S 2006 Functionalized imidazolium salts for task- synthesized complexes showed reasonable antibacterial specific ionic liquids and their applications Chem. Com- activity against the tested bacteria. Cu(II) complex (5) mun. 1049 9 Page 8 of 9 J. Chem. Sci. (2018) 130:9

13. Luo S, Mi X, Zhang L, Liu S, Xu H and Cheng J P 29. Song G, Cai Y and Peng Y 2005 Amino-functionalized 2007 Functionalized ionic liquids catalyzed direct aldol ionic liquid as a nucleophilic scavenger in solution phase reactions Tetrahedron 63 1923 combinatorial synthesis J. Comb. Chem. 7 561 14. Bates E D, Mayton R D, Ntai I and Davis J H 2002 CO2 30. Li B, Li Y Q and Zheng J 2010 A novel ionic liquid- Capture by a Task-Specific Ionic Liquid J. Am. Chem. supported Schiff base ligand applied in the Pd-catalyzed Soc. 124 926 Suzuki-Miyaura coupling reaction Arkivoc IX 163 15. D’Anna F, Marullo S and Noto R 2008 Ionic liq- 31. Clinical and Laboratory Standards Institute (NCCLS) uids/[bmim][n3] mixtures: Promising media for the 2006 Performance Standards for Antimicrobial Disk synthesis of aryl azides by snar. J. Org. Chem. 73 6224 Susceptibility Tests: Approved Standard, 9th ed. M2-A9, 16. Davis Jr J H 2004 Task-specific ionic liquids Chem. Lett. Wayne, PA 33 1072 32. Clinical and Laboratory Standards Institute (NCCLS) 17. Tang S, Babai A and Mudring A V 2008 Europium- 2006, Methods for Dilution Antimicrobial Susceptibil- basierte ionische Flüssigkeiten als lumineszierende ity Tests for Bacteria that Grow Aerobically: Approved weiche Materialien Angew. Chem. 120 7743 Standard, 7th ed. M7-A7, Wayne, PA 18. Patel S A, Sinha S, Mishra A N, Kamath B V and Ramb 33. Yõldõz M, Kõlõc Z and Hökelek T 1998 Intramolecular R N 2003 Olefin epoxidation catalysed by Mn(II) Schiff hydrogen bonding and tautomerism in Schiff bases. Part base complex in heterogenisedÐhomogeneous systems I. Structure of 1,8-di[N-2-oxyphenyl-salicylidene]-3,6- J. Mol. Catal. A 192 53 dioxaoctane J. Mol. Struct. 441 1 19. Peng Y, Cai Y, Song G and Chen J 2005 Ionic Liquid- 34. Yeap G -Y, Ha S -T, Ishizawa N, Suda K, Boey P ÐL Grafted Mn(III)-Schiff Base Complex: A Highly Effi- and Mahmood W A K 2003 Synthesis, crystal structure cient and Recyclable Catalyst for the Epoxidation of and spectroscopic study of parasubstituted 2-hydroxy- Chalcones Synlett 14 21470 3-methoxybenzalideneanilines J. Mol. Struct. 658 87 20. Hadjikakou S K and Hadjiliadis N 2009 Antiproliferative 35. Abdel-Latif S A, Hassib H B and Issa Y M 2007 Studies and anti-tumor activity of organotin compounds Coord. on some salicylaldehyde Schiff base derivatives and their Chem. Rev. 253 235 complexes with Cr(III), Mn(II), Fe(III), Ni(II) and Cu(II) 21. Garoufis A, Hadjikakou S K and Hadjiliadis N 2009 Spectrochim. Acta A 67 950 Palladium coordination compounds as anti-viral, anti- 36. Wang J, Pei Y,Zhao Y and Hu Z 2005 Recovery of amino fungal, anti-microbial and anti-tumor agents Coord. acids by imidazolium based ionic liquids from aqueous Chem. Rev. 253 1384 media Green Chem. 196 22. Patil S A, Naik V H, Kulkarni A D and Badami P S 2010 37. Han D and Row K H 2010 Recent application of ionic DNA cleavage, antimicrobial, spectroscopic and fluores- liquids in separation technology Molecules 15 2405 cence studies of Co(II), Ni(II) and Cu(II) complexes with 38. Mahmoud M A, Zaitone S A, Ammar A M and Sallam S SNO donor coumarin Schiff bases Spectrochim. Acta A A 2016 Synthesis, structure and antidiabetic activity of 75 347 chromium(III) complexes of metformin Schiff-bases J. 23. Dinda R. Saswati R, Schmiesing C S, Sinn E, Patil Mol. Struct. 1108 60 Y P, Nethaji M, Stoeckli-Evans H and Acharyya R 39. Kohawole G A and Patel K S 1981 The stereochemistry 2013 Novel metal-free, metallophthalocyanines and their of oxovanadium(IV) complexes derived from salicy- quaternized derivatives: Synthesis, spectroscopic char- laldehyde and polymethylenediamines J. Chem. 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Sci. 14 5 26. Grasselli R K 1999 Advances and future trends in selec- 43. Nehra P, Khungar B, Pericherla K, Sivasubramanian S tive oxidation and ammoxidation catalysis Catal. Today C and Kumar A 2014 Imidazolium ionic liquid-tagged 49 141 Palladium complex: An efficient catalyst for Heck and 27. Saha S, Brahman D and Sinha B 2015 Cu(II) Suzuki reactions in aqueous medium Green Chem. 14 complexes of an ionic liquid-based Schiff base 4266 [1-2-((2-hydroxybenzylidene) amino)ethyl-3- 44. Li B, Li Y Q, Zheng W J and Zhou M Y 2009 Synthesis methylimidazolium]PF6: Synthesis, characterization of ionic liquid supported Schiff bases Arkivoc 11 165 and biological activities J. Serb. Chem. Soc. 80 35 45. Silverstein R M 2005 In Spectrometric Identification of 28. Saha S, Das A, Acharjee K and Sinha B 2016 Synthesis, Organic Compounds 7th edn. (Location: John Wiley) characterization and antibacterial studies of Mn(II) and 46. Peral F and Gallego E 1997 Self-association of imidazole Co(II) complexes of an ionic liquid tagged Schiff base J. and its methyl derivatives in aqueous solution. A study Serb. Chem. Soc. 80 1151 by ultraviolet spectroscopy J. Mol. Struct. 415 187 J. Chem. Sci. (2018) 130:9 Page 9 of 9 9

47. Shakir M, Nasam O S M, Mohamed A K and Varkey 50. Natarajan C, Tharmaraj P and Murugesan R 1992 S P 1996 Transition metal complexes of 13Ð14- In Situ Synthesis and Spectroscopic Studies of Cop- membered tetraazamacrocycles: Synthesis and charac- per(II) and Nickel(II) Complexes of 1-Hydroxy-2- terization Polyhedron 15 1283 Naphthylstyrylketoneimines J. Coord. Chem. 26 48. Chem L S and Cummings S C 1978 Synthesis and char- 205 acterization of cobalt(II) and some nickel(II) complexes 51. Dehghanpour S, Bouslimani N, Welter R and Mojahed with N,N’-ethylenebis(p-X-benzoylacetone iminato) F 2007 Synthesis, spectral characterization, proper- and N,N’-ethylenebis(p-X-benzoylmonothioacetone ties and structures of copper(I) complexes containing iminato) ligands Inorg. Chem. 17 2358 novel bidentate iminopyridine ligands Polyhedron 26 49. Del Paggio A A and McMillin D R 1983 Substituent 154 effects and the photoluminescence of Cu(PPh3)2(NN)+ 52. Lever A B P 1984 In Inorganic Electronic Spectroscopy systems Inorg. Chem. 22 691 2nd edn. (Amsterdam: Elsevier)

J. Serb. Chem. Soc. 81 (10) 1151–1159 (2016) UDC 546.712+546.732:542.913+544.275– JSCS–4915 128:542.9+547.571’551:615.281 Original scientific paper

Synthesis, characterization and antibacterial studies of Mn(II) and Co(II) complexes of an ionic liquid tagged Schiff base SANJOY SAHA1, ANANYA DAS2, KAUSHIK ACHARJEE2 and BISWAJIT SINHA2* 1Department of Chemistry, Kalimpong College, Kalimpong-734301, India and 2Department of Chemistry, University of North Bengal, Darjeeling-734013, India (Received 25 April, revised 13 June, accepted 1 July 2016) Abstract: Mn(II) and Co(II) complexes of an ionic liquid-based Schiff base, 1-{2-[(2-hydroxybenzylidene)amino]ethyl}-3-methyl-1H-imidazolium bromide, were synthesized and characterized by various analytical and spectroscopic methods, such as elemental analysis, UV–Vis, FT-IR, 1H-NMR, ESI-MS and magnetic susceptibility measurement. These studies indicated tetrahedral geometry for the complexes. The Schiff base ligand and its complexes were tested for in vitro antibacterial activities to assess their inhibiting potentials against Escherichia coli and Lactobacillus sp. Keywords: 1-methylimidazole; 2-bromoethylamine hydrobromide; salicylaldehyde; 1-{2-[(2-hydroxybenzylidene)amino]ethyl}-3-methyli-1H-midazolium bromide.

INTRODUCTION Ionic liquids (ILs) are generally based on inorganic or organic anions paired with large, usually asymmetric organic cations, have low melting points below 373 K although many are in fact liquid at/below ambient temperature.1,2 They are worthy of extensive investigation because of their unique physical and chemical properties, such as non-volatile, non-flammable, thermally stable and recyclable. In addition to these just mentioned properties, ILs exhibit a wide electrochemical window, high ionic conductivity, a broad temperature range of the liquid state and frequently possess excellent chemical inertness as well.3–5 The hydrophobicity/hydrophilicity and other physical features of ionic liquids including density, melting point, conductivity, polarity, Lewis acidity, viscosity, enthalpy of vaporization can be altered by manipulating the structure of cations and anions6 and issues such as their toxicity and biodegradability are now being explored to judge them as potentially green replacements for traditional molecular solvents.7 To date, ILs have been used in organic synthesis, catalysis, industrial

* Corresponding author. E-mail: [email protected] doi: 10.2298/JSC160425065S

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processing, electrochemistry, pharmaceutics, biotechnology, nano-chemistry, analytical chemistry and separation technologies. Ionic liquids shaped for a particular function are referred to as functionalized ionic liquids (FILs). Recently, much attention has been paid to the preparation and application of FILs with special tasks carrying functional groups such as hydroxyl, amino, sulphonic acid, carbonyl, etc.8–12 The increasing popularity of FILs lies in the fact that both the cationic and anionic parts can be altered and applied to a specific application. Again, the incorporation of functional groups can impart a particular capability to ILs by increasing their catalytic stability and reducing catalytic leaching.12,13 Imidazolium-based systems play important roles in biochemical processes14 having varied pharmacological properties. Schiff bases and their metal complexes play a significant role in the field of coordination chemistry and have been studied extensively; transition metal complexes of Schiff bases with oxygen and nitrogen donors are of particular interest because of their ability to possess unusual configurations and structure-related bioactivities.15–17 Hence herein, the synthesis of an imidazolium ionic liquid-tagged Schiff base 1-{2-[(2-hydroxybenzylidene)amino]ethyl}-3-methyl-1H-imidazolium bromide (LH) and its Mn(II) and Co(II) complexes are reported. The synthesized compounds were characterized by various analytical and spectroscopic methods. The Schiff base and its complexes were tested for their in vitro antibacterial activity against Escherichia coli and Lactobacillus sp. EXPERIMENTAL Materials and methods All the reagents were of analytical grade and used without further purification. 1-Methyl- imidazole and 2-bromoethylamine hydrobromide were procured from Sigma–Aldrich, Ger- many. Salicylaldehyde, Mn(OCOCH3)2·4H2O, Co(OCOCH3)2·4H2O and all other chemicals were used as received from SD Fine Chemicals, India. The IR spectra were recorded in KBr pellets using a Perkin–Elmer Spectrum FT-IR spectrometer (RX-1) operating in the region 4000 to 400 cm-1. The 1H-NMR spectra were recorded at room temperature on a FT-NMR (Bruker Advance-II 400 MHz) spectrometer using DMSO-d6 and D2O as solvents. Chemical shifts are quoted in ppm downfield of the internal standard tetramethylsilane (TMS). Ele- mental microanalyses (C, H and N) were conducted on a Perkin–Elmer (model 240C) analyzer. The metal contents were determined by AAS (Varian, SpectrAA 50B) using standard metal solutions from Sigma–Aldrich, Germany. The mass spectra were recorded on a JMS- -T100LC spectrometer. The purity of the synthesized compounds was checked by thin layer chromatography (TLC) on silica gel plates. The UV–Vis spectra were recorded in methanol using a Jasco V-530 spectrometer. The magnetic susceptibilities were measured at room temperature with a Sherwood Scientific Ltd. magnetic susceptibility balance (Magway MSB Mk1). The molar conductance was measured with a Systronics conductivity TDS meter (Model-308) with a cell (Type CD-30, cell constant 0.10±10%) at 298.15±0.01 K. Antibac- terial activities (in vitro) of the synthesized ligand and the complexes were studied by the disc diffusion method against two bacteria, viz., Lactobacillus sp. (ATCC No. 33222) and Esche- richia coli (ATCC No. 69905) with respect to the standard drug ampicilin.

Synthesis of the imidazolium ionic liquid 3-(2-aminoethyl)-1-methyl-1H-imidazolium bromide ([2-aemim]Br, 1) The amino functionalized ionic liquid was prepared following a literature procedure.18 A mixture of 1-methylimidazole (4.10 g, 0.05 mol) and 2-bromoethylamine hydrobromide (10.25 g, 0.05 mol) in ethanol (50 mL) was refluxed under a nitrogen atmosphere at 80 °C for 24 h. On completion of the reaction, the solvent was distilled off and the residue recrystallized from ethanol and ethyl acetate. The resultant white powder was dissolved in methanol and then NaOH (2.00 g, 0.05 mol) was added to react for 8 h at room temperature. The excess NaOH was filtered off and the solvents were evaporated under vacuum. The obtained product was washed repeatedly with diethyl ether. After drying for 6 h under vacuum at 80 °C, the expected ionic liquid was obtained as a light-yellow oil. Yield: 69 %. Synthesis of imidazolium ionic liquid-tagged Schiff base, LH (2) A mixture of salicylaldehyde (1.22 g, 10 mmol) and [2-aemim]Br (2.06 g, 10 mmol) was stirred at room temperature for 12 h without a solvent, followed by washing with diethyl ether (3×30 mL) and vacuum evaporation which gave the product as a brown oil. Yield: 65–70 %. Synthesis of metal complexes 3 and 4 To 20 mL of an ethanolic solution of ligand, LH (0.50 g, 1.30 mmol), metal acetate, viz., Mn(CH3COO)2·4H2O (0.173 g, 0.65 mmol) or Co(CH3COO)2·4H2O (0.16 g, 0.65 mmol) dissolved in ethanol was added and the mixture was refluxed for 8 h until the starting materials had been completely consumed as monitored by TLC. On completion of the reaction, the solvent was evaporated and the reaction mixture was cooled to room temperature. The precipitate was filtered, washed successively with ethanol (3×10 mL) and dry ether (3×10 mL) and finally dried in a desiccator to obtain the solid product. A schematic representation of the synthesis is shown in Scheme 1.

Scheme 1. Synthesis of the ionic liquid-based Schiff base [1-{2-[(2-hydroxybenzylidene)- amino]ethyl}-3-methyl-1H-imidazolium bromide (LH, 2), from ionic liquid 1, and M(II) complexes 3 and 4 from LH (2).

The characterisation data for the ionic liquid, the ionic liquid-tagged Schiff base and the metal complexes are given in the Supplementary material to this paper. RESULTS AND DISCUSSION The complexes are moisture sensitive but stable in vacuum desiccator and soluble in N,N-dimethylformamide, dimethyl sulphoxide, acetonitrile and methanol. All the isolated compounds were found to be hygroscopic in nature and were characterized by different analytical and spectroscopic methods. IR spectral studies The IR spectra of the Schiff base LH (2) and its Mn(II) and Co(II) complexes (3 and 4, respectively) are given in Fig. 1.

Fig.1. FTIR spectra of: A) 1-{2-[(2-hydroxybenzylidene)amino]ethyl}-3-methyl- -1H-imidazolium bromide (2); B) the Mn(II) complex (3) and C) the Co(II) complex (4).

The IR spectra of the complexes were compared to that of the free ligand in order to determine the coordination sites involved in the complexation. IR spectrum of the ligand showed a strong broad band at 3429–3143 cm–1; this band was attributed to the –OH of the phenolic group hydrogen bonded with the H–C(=N) group of the ligand (OH…N=C).19 The broad band that appeared in the range 3398–3423 cm–1 in the spectra of the Mn(II) and Co(II) complexes was due to

absorption of water molecules, as reported earlier by Gruzdev et al.20 The band at 1454 cm–1 observed for the phenolic –CO of the free ligand was shifted to a lower frequency region, 1444–1449 cm–1, for the complexes21 on chelation. In the ligand, a band corresponding to the azomethine group (–C=N) was found at 1626 cm–1. On complexation, this band was shifted to the range of 1616–1601 cm–1. This indicated the involvement of N-atom of azomethine (–C=N) group in complex formation.22 Therefore, the IR spectra suggest that the ligand (LH) coordinates to the metal ions (Mn2+and Co2+) through the N-atom of the azomethine (–C=N) group and the O-atom of the phenolic group (Ar-O). The peak in the range 756–761 cm–1 in the spectra of complexes was assigned to bromide. The new bands appearing in the regions 565–590 cm–1 and 460–475 cm–1 in the spectra of Mn(II) and Co(II) complexes could tentatively be assigned to the M–O and M–N stretching frequencies, respectively.23 Mass spectral studies The mass spectra of the ligand (LH) showed molecular ion peak at m/z 227 + corresponding to [M–3H–Br] , where M stands for C13H16N3OBr. The mass spectra of the Mn(II) complex (3) showed peaks at m/z 675, 503, 401, 321, 251, 169 and 121, whereas the Co(II) complex (4) displayed peaks at m/z 679, 409, 330, 245, 148 and 124. The molecular ion peaks at m/z 675 and 679 could be assigned to (M + 4H), where M stands for C26H30MnN6O2Br2 and C26H30CoN6O2Br2 for Mn(II) and Co(II) complexes, respectively. The different molecular ion peaks of the complexes could be attributed to different fragmentations of the metal complexes by successive rupture of different bonds in their structures. The mass fragmentations of complexes are given in Figs. S-1 and S-2 of the Supplementary material. The mass spectra of the ligand and complexes show good correlation with the respective structures as revealed by the elemental and other spectral analysis. NMR spectral studies 1 The H-NMR spectrum of the ligand was recorded in DMSO-d6 and the spectrum showed well resolved signals, as expected. The 1H-NMR of the ligand showed a singlet at δ 3.95 ppm (3H, s, CH3), a triplet at δ 4.58 ppm (2H, t, CH2), a triplet at δ 4.68 ppm (2H, t, CH2), a multiplet at δ 7.72–7.83 ppm (4H, m, Ar-H), a singlet at δ 7.90 (1H, s, NCH) and a singlet at δ 7.92 ppm (1H, s, NCH). 1H-NMR spectrum of the ligand also showed a sharp singlet at δ 9.20 ppm assignable to the proton of the azomethine group (–CH=N–), presumably due to the effect of the ortho-hydroxyl group in the aromatic ring. A singlet in the downfield region at δ 8.31 ppm could be ascribed to the phenolic proton. The Schiff base displayed a downfield shift of the –OH proton due to intermolecular

(O–H…N) hydrogen bonding interactions.24 The 1H-NMR spectrum of the cationic moiety of the ligand was almost the same as that previously reported in the literature.25,26 Molar conductance measurements

The molar conductance values of the complexes (Λm) were obtained from the relation Λm = 1000κ/c, where c and κ stand for the molar concentration and specific conductance of the metal complexes, respectively. The complexes (1.8×10−3 M) were dissolved in N,N-dimethylformamide and their specific conductivities were measured at 25 °C. The molar conductance values were found to be in the range 212–238 Ω–1 cm–1 mol–1, indicating their 1:2 electrolytic (M:L) behaviour.27 Electronic absorption spectral and magnetic moment studies The UV–Vis spectra of the ligand and the metal complexes (as depicted in Fig. 2) were recorded in methanol at ambient temperature. The electronic absorption spectrum of the ligand (2) showed three absorption bands at 318, 255 and 214 nm, respectively due to n→π* and π→π* transitions and transitions involving the imidazolium moiety.28,29 The Mn(II) complex (3) showed three absorption bands at 314, 255 and 211 nm; that is the ligand band at 318 nm showed a hypsochromic shift probably due to coordination with Mn2+ (d5) ion. The Co(II) complex (4) also showed three absorption bands at 220, 248 and 403 nm due to 4 4 4 4 4 4 A2→ T1(P), A2→ T1(F) and A2→ T2 transitions, respectively. Thus, UV–

Wavelength, nm

Fig. 2. The UV–Vis spectra of the ligand (2), the Mn(II) complex (3) and the Co(II) complex (4).

–Vis spectra of both the complexes suggest no Jahn–Teller distortion and tetrahedral geometry is thus suggested for both the complexes.30 This fact was substantiated by the results obtained from IR, ESI-MS, UV–Vis spectra and the measured magnetic moments (5.86 and 4.67 μB for the Mn(II) and Co(II) complexes, respectively). Antibacterial activities The Schiff base ligand and their metal complexes were studied against the gram negative bacteria Escherichia coli and gram positive bacteria Lactobacillus sp. to assess their potentials as antibacterial agents. Stock solutions of the synthesised compounds were prepared by dissolving the compounds in dimethyl sulphoxide and serial dilutions of the solutions were made with sterile distilled water for different concentrations to determine the minimum inhibition concentration (MIC). The concentrations of the tested compounds were 31, 62, 125 and 250 µg mL–1 in comparison to the standard drug ampicillin (100 μg mL– 1). The nutrient agar medium was poured into 0.5 mL culture contained in Petri dishes and the well diffusion technique31,32 was applied. The Petri dishes were placed in an incubator at 37 °C for 24 h. No significant inhibition zones surrounding the well were observed against the complexes (the inhibition zones against Escherichia coli are shown in Fig. 3), but the ligand showed very low antibacterial activities with well diameters in the range of 1.0–1.2 mm at a concentration of 250 µg mL–1 against the studied bacteria.

Fig. 3. Inhibition zones for anti-bacterial activities: A) 1-{2-[(2-hydroxybenzylidene)amino]- ethyl}-3-methyl-1H-imidazolium bromide (2); B) the Mn(II) complex (3) and C) the Co(II) complex (4) against Escherichia coli.

CONCLUSIONS Herein, the synthesis and physicochemical characterization of an imidazolium ionic liquid-tagged Schiff base, i.e., 1-{2-[(2-hydroxybenzylidene)amino]- ethyl}-3-methyl-1H-imidazolium bromide, and its Mn(II) and Co(II) complexes were described. Different analytical and spectral studies revealed that the Schiff base acts as a bidentate ligand that coordinates through the azomethine nitrogen and phenolic oxygen atoms to Mn(II) and Co(II) ions and thus formed tetrahedral 1:2 (M:L) complexes. The synthesized compounds were tested for their antibacterial activities against the bacteria Escherichia coli and Lactobacillus sp.

The observed minimum inhibition (MIC) zones suggested that the synthesized complexes have no significant antibacterial activities against the bacteria Escherichia coli and Lactobacillus sp. SUPPLEMENTARY MATERIAL Characterization data and mass fragmentation schemes are available electronically at the pages of journal website: http://www.shd.org.rs/JSCS/, or from the corresponding author on request. Acknowledgements. The authors are grateful to the Departmental Special Assistance Scheme under the University Grants Commission, New Delhi (SAP-DRS-III, NO.540/12/ /DRS/2013) for financial support and SAIF, NEHU, Shilong, India for the 1H-NMR, ESI-MS and elemental analyses. One of the authors (K. A) is thankful to UGC, New Delhi, India, for granting him a UGC-BSR Fellowship (Ref. F.25-1/2013-14(BSR)).

ИЗВОД СИНТЕЗА, КАРАКТЕРИЗАЦИЈА И АНТИБАКТЕРИЈСКА ИСПИТИВАЊА Mn(II) И Co(II) КОМПЛЕКСА СА ЈОНСКОМ ТЕЧНОСТИ ИЗ ГРУПЕ ШИФОВИХ БАЗА КАО ЛИГАНДОМ

SANJOY SAHA1, ANANYA DAS2, KAUSHIK ACHARJEE2 и BISWAJIT SINHA2 1Department of Chemistry, Kalimpong College, Kalimpong-734301, India и 2Department of Chemistry, University of North Bengal, Darjeeling-734013, India Синтетисани су Mn(II) и Co(II) комплекси са јонском течности из групе Шифових база као лигандом, 1-{2-[(2-хидроксибензилиден)амино]етил}-3-метил-1H-имида- золијум-бромидом. Комплекси су окарактерисани применом различитих аналитичких и спектроскопских метода, као што су елементална анализа, UV–Vis, FT-IR, 1H-NMR, ESI- MS и магнетна мерења. На основу ових испитивања закључено је да комплекси имају тетраедарску геометрију. Лиганд типа Шифове базе и одговарајући комплекси су in vitro испитивани на антибактеријску активност према Escherichia coli и Lactobacillus sp. сојевима. (Примљено 25. априла, ревидирано 13. јуна, прихваћено 1. јула 2016)

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