Synthesis and reactivity of cyclopentadienyl based organometallic compounds and their electrochemical and biological properties Sasmita Mishra Department of Chemistry National Institute of Technology Rourkela Synthesis and reactivity of cyclopentadienyl based organometallic compounds and their electrochemical and biological properties Dissertation submitted to the National Institute of Technology Rourkela In partial fulfillment of the requirements of the degree of Doctor of Philosophy in Chemistry by Sasmita Mishra (Roll Number: 511CY604) Under the supervision of Prof. Saurav Chatterjee February, 2017 Department of Chemistry National Institute of Technology Rourkela Department of Chemistry National Institute of Technology Rourkela Certificate of Examination Roll Number: 511CY604 Name: Sasmita Mishra Title of Dissertation: ''Synthesis and reactivity of cyclopentadienyl based organometallic compounds and their electrochemical and biological properties We the below signed, after checking the dissertation mentioned above and the official record book(s) of the student, hereby state our approval of the dissertation submitted in partial fulfillment of the requirements of the degree of Doctor of Philosophy in Chemistry at National Institute of Technology Rourkela. We are satisfied with the volume, quality, correctness, and originality of the work. --------------------------- Prof. Saurav Chatterjee Principal Supervisor --------------------------- --------------------------- Prof. A. Sahoo. Prof. G. Hota Member (DSC) Member (DSC) --------------------------- --------------------------- Prof. R. Dinda Member (DSC) Examiner Prof. N. Panda Chairman (DSC) Department Of Chemistry National Institute of Technology Rourkela Prof. Saurav Chatterjee Associate Professor, Department of Chemistry NIT, Rourkela February 16, 2017 Supervisor's Certificate This is to certify that the work presented in this dissertation entitled ''Synthesis and reactivity of cyclopentadienyl based organometallic compounds and their electrochemical and biological properties'' by ''Sasmita Mishra'', Roll Number 511CY604, is a record of original research carried out by her under my supervision and guidance in partial fulfillment of the requirements of the degree of Doctor of Philosophy in Chemistry. Neither this dissertation nor any part of it has been submitted for any degree or diploma to any institute or university in India or abroad. Prof. Saurav Chatterjee Dedicated to my loving parents Declaration of Originality I, Sasmita Mishra, Roll Number 511CY604 hereby declare that this dissertation entitled ''Synthesis and reactivity of cyclopentadienyl based organometallic compounds and their electrochemical and biological properties'' represents my original work carried out as a doctoral student of NIT Rourkela and, to the best of my knowledge, it contains no material previously published or written by another person, nor any material presented for the award of any other degree or diploma of NIT Rourkela or any other institution. Any contribution made to this research by others, with whom I have worked at NIT Rourkela or elsewhere, is explicitly acknowledged in the dissertation. Works of other authors cited in this dissertation have been duly acknowledged under the section ''Bibliography''. I have also submitted my original research records to the scrutiny committee for evaluation of my dissertation. I am fully aware that incase of any non-compliance detected in future, the Senate of NIT Rourkela may withdraw the degree awarded to me on the basis of the present dissertation. February 16, 2017 NIT Rourkela Sasmita Mishra Abstract The current focus of organometallic chemistry is based upon their synthesis, eloectrochemical properties, diverse biological behavior and their facet towards a new field of bioorganometallics concerning both organometallic and coordination chemistry. Organometallic complexes involving metal - cyclopentadienyl linkages have been an important fragment due to their unique structural variety, stability and their potential applications in organic synthesis, catalysis, bioorganometallic, advance materials, molecular recognition etc. Ferrocene and its derivatives are the most versatile aspect in organometallic chemistry because of their unique structural integrity, reversible redox behavior and have been responsible for the development of material science, molecular wires, catalysis, molecular recognition, sensing, electronic communication, bio-conjugates and medicinal chemistry. The use of ferrocenyl compounds as bioactive molecule has been established recently and several reports show that a large number of ferrocene containing compounds display interesting cytotoxic and DNA cleaving activities. Ferrocene substituted tamoxifen and chloroquine derivatives are among the many examples where systematic functionalization of ferrocene has improved the cytotoxic activity of the standard drug itself. In parallel, the half sandwich based organometallic compounds are also drawing interest because their various biological properties ranging from antimalarial, antimicrobial, anticancer, enzyme inhibitors and phototoxicity. Half sandwich compounds containing metal carbonyls are the most significant ligands in medicinal chemistry and can play a vital role as tracers in immunological analysis based on several analytical methods like FTIR, electrochemical, atomic absorption techniques etc. Moreover, ferrocenyl Schiff base compounds have been reported for their interesting coordination features and exciting biological properties. In view of the enormous potential applications of ferrocenyl and half sandwich based organometallic compounds, we focused our study to synthesize some sandwich and half sandwich based Schiff base compounds and to study their biological properties. We have been able to synthesize a range of novel ferrocene and cymantrene based Schiff base compounds and characterize by spectroscopic and crystallographic technique. We have also described the synthesis of hetero-bimetallic chalcones containing both ferrocenyl and cymantrenyl fragments and studied their reactivity towards mono- and diphosphine substitution. In addition, compounds containing multiple redox centers have also been highly focused due to their various application related to electronic communication, sensors and molecular wires. In this regard, we focused on the synthesis of diferrocenyl bifunctional molecular systems containing both hydrazone and enone units using simple and systematic synthetic route. Efforts have been made to study the unique structural feature and to understand the biological and sensing properties of some of the compounds. We have carried out cyclic-voltammetric studies with different analogs of the diferrocenyl compounds to understand the electronic communication behavior inside the molecule. DFT calculation was also performed to establish some of the interesting features related to structural stability, metal ion interaction and molecular orbital energies. Keywords: Ferrocenyl, Cymantrenyl, Chalcone, Hydrazone, Bioorganometallic, Electronic communication Contents Page Certificate of Examination ii Supervisor's Certificate iii Dedication iv Declaration of Originality v Abstract vi Contents vii Acknowledgements xi Bio-data xii Chapter 1: Introduction 1 1.1. Metal-cyclopentadienylcomplex 2 1.1.1. Cyclopentadienyl ligand 3 1.1.2. Bonding modes of cyclopentadienyl ligand 4 1.1.3. Classification of cyclopentadienyl complexes 12 1.2. Structural variety of metal cyclopentadienyl complex 15 1.2.1. Half sandwich and Piano stool complexes 16 1.2.2. Sandwich complexes 22 1.2.3. Other variety of metallocenes 24 1.2.4. Bent metallocenes 26 1.2.5. Bimetallic cyclopentadienyl complexes 27 1.2.6. Multimetallic cyclopentadienyl complexes 30 1.2.7. Multidecker sandwich compounds 31 1.3. Cymantrene based organometallic compounds 33 1.3.1. Chelated Cymantrenyl complex 36 1.3.2. Biological properties 39 1.3.3. Electrochemical properties 42 1.4. Ferrocene based organometallic compound 44 vii 1.4.1. C-H bond functionalization of ferrocene 47 1.4.2. Ferrocenyl derivatives having biological properties 49 1.4.3. Ferrocenyl compounds as biosensor 55 1.4.4. Ferrocenyl compounds as chemosensor 57 1.4.5. Electronic communication in ferrocene based molecules 61 1.4.6. Diferrocenyl organometallic compounds 64 1.5. Half-sandwich and ferrocenyl conjugate system 69 1.6. References 73 Chapter 2: Synthesis, characterization and structural evaluation of 82 cymantrenyl hydrazone derivatives 2.1. Introduction 83 2.2. Experimental Sections 89 2.2.1. General Procedures 89 5 2.2.2. Synthesis of [(CO)3Mn{( -C5H4)C(CH3)═NN(H)C(O)R}] 89 (1-4) 2.2.3. Crystal structure determination for 1 and 2 90 2.2.4. Antibacterial activity 91 2.3. Results and Discussion 92 2.3.1. Molecular structure of 1 - 3 93 2.3.2. Antibacterial activity of 1 - 3 98 2.4. References 100 Chapter 3: Synthesis, characterization and redox properties of 103 unsymmetrically substituted 1,1’ ferrocenyl dihydrazone compound 3.1. Introduction 104 3.2. Experimental Sections 108 3.2.1. General Procedures 108 5 5 3.2.2. Synthesis of 1,1’-[{CH3C(O)( -C5H4)}Fe{( -C5H4)C(CH3)═N 108 N(H)C(O)R}] (5-8) 3.2.3. Reaction of 7 with hydrazide 110 viii 3.2.4. Crystal structure determination for 7 110 3.3. Results and Discussion 112 3.4. References 119 Chapter 4: Ferrocenyl-cymantrenyl hetero-bimetallic chalcones: Synthesis, 121 reactivity and biological properties 4.1. Introduction 122 4.2. Experimental Sections 126 4.2.1. General Procedures 126 5 5 5 4.2.2.