STUDIES ON CHEMISTRY OF SOME POLYDENTATE LIGANDS AND THEIR METAL COMPLEXES

Abstract

The coordination chemistry deals with the chemistry of ligands and metal ions and the ligands play an indispensible role in determining the coordination geometry, redox chemistry and spectroscopic properties of the metal complexes. In general, ligands serve as electron donors acting as Lewis base and metals as electron acceptors acting as Lewis acid. According to Pearson‟s “Hard and Soft Acids and Bases” (HSAB) concept, stable bonds may exist only between hard acids and hard bases or soft acids and soft bases. A little modification in the ligand architecture may lead to significant improvements in the reactivities exhibited by complexes. According to Jorgenson, the ligands may be innocent or non-innocent depending on the assignment of oxidation states. Non-innocent ligands give rise to the metal complexes with intriguing redox and electronic properties. A number of non-innocent ligands are present in the biosystem and galactose oxidase enzyme is one of the best examples of such systems. Nitric oxide, porphyrinic ligands, catecholate ligands and phenolato ligands also represent this family and give rise to complexes with exciting properties. Complexes derived from such ligands receive special significance due to their resemblance with biosystems as well as due to their ability to serve as electron reservoirs. Being inspired from biology, several biomimmetic complexes have been developed which can catalyze various chemical reactions of potential biological interest like water oxidation, dinitrogen activation and amide hydrolysis at reasonable rates and under ambient conditions. A number of metal complexes have been prepared using planar ligands like bipy, o-phen, dpq, dppz and terpy which can interact with nucleic acids and such complexes are of medicinal values. Such compounds find their application in developing the foot-printing agents, conformational probes and chemotherapeutic agents. Hence, judicial design of the ligand frame is the essential step to finely tune the properties and reactivities exhibited by the metal complexes. In the present study, few ligands were designed, synthesized and characterized by several spectroscopic studies. Cobalt, nickel, copper and zinc complexes were synthesized and characterized by spectroscopic and electrochemical studies. Molecular structures of representative metal complexes were determined by single crystal X-ray diffraction. Various type of biological activities were examined for these complexes including DNA interaction v studies, nuclease activity, superoxide dismutase activity, phenoxyl radical generation, catecholase activity, protein interaction studies, protein cleavage activity and anticancer activity. The effect of donor atoms and ligand structure on reactivity studies was investigated in this thesis. The thesis is divided into following chapters. The First chapter presents an introduction to coordination chemistry of various types of ligands as well as to the general properties of few first row transition metals. Role of ligand to determine the chemical properties and biological activities of various coordination complexes is thoroughly discussed. A number of ligands were described which were used for the structural/functional mimicking of the active sites of various metalloenzymes. Various physical methods and spectroscopic techniques used were comprehensively summarized in this chapter. Chapter two presents the synthesis and characterization of mononuclear cobalt complexes namely [Co(Pyimpy)Cl2] (1a), [Co(Pyimpy)2](ClO4)2 (1b), [Co(Pamp)Cl2] (2a) and [Co(Pamp)2](ClO4) (2b) (where Pyimpy = 1phenyl1(pyridin2yl)2(pyridin2ylmethylene)hydrazine; PampH = N'phenylN'(pyridin2yl)picolinohydrazide and H stands for the dissociable proton). The molecular structure of complex 1a was authenticated using Xray diffraction study. Redox behavior of the metal complexes was investigated through electrochemical methods. DNA interaction and nuclease activity studies over all the complexes were performed and the mechanism of DNA cleavage was established using various types of scavengers. Superoxide dismutase (SOD) activity of the complexes was assayed by xanthine/xanthine oxidase/nitroblue tetrazolium assay and a correlation was developed with the DNA cleavage activity. Chapter three describes the synthesis and characterization of a tridentate ligand N3L (where N3L=2((1phenyl2(1(pyridin2yl)ethylidene)hydrazinyl)methyl)pyridine) and its mononuclear metal complexes of copper, zinc, cobalt and nickel namely [Cu(N3L)Cl2] (3a), [Cu(N3L)2](ClO4)2 (3b), [Zn(N3L)Cl2] (4a), [Zn(N3L)2](ClO4)2 (4b), [Co(N3L)Cl2] (5a), [Co(N3L)2](ClO4)2 (5b), [Ni(N3L)Cl2] (6a) and [Ni(N3L)2](ClO4)2 (6b) respectively. The structures of complexes 3a and 5a were established by X-ray diffraction methods. Cyclic voltammetric experiments were performed to examine the redox properties of the metal complexes. All the complexes were found to be stable in the buffer solutions at vi physiological pH and subjected to DNA interaction studies by absorption spectroscopy, emission spectroscopy and circular dichroism spectroscopy. The complexes represent the rare kind of complexes which bind covalently with nucleic acids and the mechanism has been established by titration with potential small ligands using absorption spectral technique. The DNA cleavage activities of the complexes were investigated and the mechanisms were determined using inhibition experiments involving radical scavengers. Binding of these complexes with bovine serum albumin (BSA) was also investigated. The mechanism of binding with protein was explored by the titration of these complexes with amino acids using electronic absorption spectroscopy and a covalent attachment of metal complexes with the amino acids side chains was observed. The family represents novel examples of complexes which are still less explored and highly desirable for in vivo applications. In chapter four, two mononuclear cobalt(III) complexes namely [Co(Phimp)2](ClO4)∙CH3CN (7∙CH3CN) and [Co(tBuPhimp)2](ClO4) (8) derived from tridentate ligands PhimpH and tBuPhimpH (PhimpH = 2((2phenyl2(pyridin2yl)hydrazono)methyl)phenol and tBuPhimpH = 2,4ditertbutyl6((2phenyl2(pyridin2yl)hydrazono)methyl)phenol where H stands for the dissociable proton) were synthesized and characterized by various physical and spectroscopic techniques. Xray crystallographic studies were performed to determine the molecular structure of the representative complex 7∙CH3CN. These complexes gave rise to the phenoxyl radical species in solution on chemical oxidation due to the noninnocent character of the ligands. Such species are very much significant to understand the mechanism of galactose oxidase enzyme. Generation of phenoxyl radical species was confirmed by UVvisible and EPR spectroscopy. The complexes were subjected to DNA cleavage activity and the complex 8 was found to be very efficient for DNA cleavage leading to extensive DNA degradation. Protein interaction studies of these complexes were performed by tryptophan fluorescence quenching assay using BSA as a protein model. Protease activity of both complexes was scrutinized and complex 8 was found to be efficient in protein cleavage also. The anticancer activities of these complexes were also studied against various cell lines and promising results were obtained for complex 8. vii In chapter five, the synthesis and characterization of nickel complexes [Ni(Phimp)2]∙3H2O∙CH3OH (9a∙3H2O∙CH3OH), [Ni(Phimp)Cl] (9b), [Ni(Phimp)(Pyimpy)](ClO4)∙H2O (9c∙H2O), [Ni(tBuPhimp)2] (10a), [Ni(tBuPhimp)Cl] (10b), and [Ni(tBuPhimp)(Pyimpy)](ClO4) (10c) was described. The molecular structures of the complexes 9a∙3H2O∙CH3OH and 9c∙H2O were determined using Xray diffraction methods. The redox behavior of these complexes was investigated using cyclic voltammetry. The ability of the complexes to generate phenoxyl radical species in solution by chemical oxidation was investigated and supported by DFT calculations. DNA and protein interaction studies of these complexes were accomplished in this chapter. Nuclease activities of these complexes and their mechanisms were also investigated. In chapter six, the fluorescence properties of two ligands Gimpy and Timpy (where Gimpy = 1,2bis(2phenyl2(pyridin2yl)hydrozono)ethane and Timpy = 1,2bis((2phenyl2(pyridin2yl)hydrozono)methyl)benzene) were examined in presence of various transition metal ions in solution and enhancement in fluorescence was observed in presence of Ni2+. To confirm the binding mode of these ligands, nickel complexes of these ligands namely [(Ni(Gimpy)(μCl))2](ClO4)2 (11) and [(Ni(Timpy)(μCl))2](ClO4)2∙2(CH3)2CO (12∙2(CH3)2CO) were synthesized and characterized. Cyclic voltammetric experiments were performed to investigate the redox behavior of these complexes. Molecular structures of Gimpy and 12∙2(CH3)2CO were determined using Xray crystallography. Chapter seven deals with the synthesis and characterization of dinuclear copper(II) and cobalt(II) complexes namely [{Cu(Simpy)(μCl)Cl}2]∙4H2O (13a∙4H2O), [{Co(Simpy)(μCl)Cl}2] (13b), [{Cu(Impy)(μCl)Cl}2] (14a) and [{Co(Impy)(μCl)Cl}2] (14b) derived from two bindentate ligands Simpy and Impy (Simpy = 2(1phenyl2(1(thiophen2yl)ethylidene)hydrazinyl)pyridine and Impy = 2(2benzylidene1phenylhydrazinyl)pyridine). Molecular structures of complexes 13∙4H2O and 14 were authenticated using Xray diffraction studies. The complexes were examined for the catecholase activity as well as DNA cleavage activity. Complex 13a∙4H2O exhibited moderate catecholase activity and excellent self-activated nuclease activity.