STUDIES ON COPPER AND ZINC COMPLEXES OF POLYDENTATE LIGANDS

Abstract

Copper and zinc both are important metal ions in the biology and have interesting coordination chemistry. Copper and zinc both possess stable 2+ oxidation state and analogous complexes of zinc in several times help to interpret the magnetic, spectroscopic, redox as well as structural properties of copper complexes. Hence in several cases investigations of chemistry of copper was followed by parallel investigation of chemistry of zinc. Copper is utilized very extensively in metalloenzymes to perform a large variety of functions from electron transfer to oxygen transport. On the other hand, zinc plays important catalytic role in several enzymatic reactions. For example, zinc is involved in hydrolytic process of peptide bond and DNA cleavage etc. Coordination chemistry of metal complexes involves the properties of metal as well as the ligands. Ligands having carboxylato, phenolato, carboxomido donors stabilize higher oxidation state of the metal; on the other hand, ligands having azomethine nitrogen, pyridine nitrogen, thiol, thioether donors stabilize lower oxidation states of metal. Different metal possesses some general and some unique properties in particular ligand environment. The metal ions can flip their oxidation states to show redox properties. Spectroscopic and electrochemical characterization of metal ligand complexes could afford interesting features which could be exploited to study their reactivities. In the present study new ligands were designed, synthesized and characterized by several spectroscopic studies. 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. The results of reactivity studies on copper and zinc complexes will be described in this thesis. The thesis is divided into following chapters. The First chapter presents a brief introduction to chemistry of copper and zinc. Several copper and zinc containing metalloenzymes and their role in biological system were discussed in this chapter. Literature on copper and zinc complexes based on structural and functional mimicking of metalloenzymes will be reviewed and their importance in different fields of bioinorganic chemistry has been discussed. The chemical system reported in this IV thesis is deeply introduced in this chapter. The various chemical methods and spectroscopic techniques used were comprehensively summarized in this chapter. Chapter two of this thesis deals with the designed tridentate ligand PhimpH (2-((2- phenyl-2-(pyridin-2-yl)hydrazono)methyl)phenol) having N2O donors. The ligand was synthesized and characterized by GC-MS and IR, UV-visible and NMR spectral studies. PhimpH binds to Cu(II) after deprotonation affording a new family of mononuclear complexes. All the complexes were characterized by elemental analysis, UV-visible and IR spectral studies. Magnetic moment data and conductivity measurement along with spectroscopic data suggested the formulation of [Cu(Phimp)(H20)]2(C104)2 (1), [Cu(Phimp)2] (2) and [Cu(Phimp)(L)] (3-5) where L are CH3COO", SCN" and N02~ respectively. The molecular structures of complexes ICH3CN and 3 were determined by single crystal X-ray diffraction. Ligand was meridionally coordinated for both complexes, however l-C^CN was found to be dinuclear whereas 3 was a mononuclear copper complex. Crystal structure of ICH3CN showed distorted square pyramidal geometry with bridging perchlorate ion, whereas the same for 3 revealed the presence of distorted square planar geometry around the metal centre. Cu—Cu distance in 1-CHsCN was 4.51 A and magnetic properties of the copper centers in ICH3CN revealed weak antiferromegnatic coupling due to perchlorate bridging. Electrochemical studies depicted Cu(II)/Cu(I) couple in the range of-0.50 to -0.65 V vs. Ag/AgCl. These data attributed to better stabilization of Cu(II) centre in complexes 2 and 3 as compared to complexes 1, 4 and 5. EPR spectral studies for complexes 4 and 5 indicated the order of covalent character in 4 > 5 with dx2-y2 orbital as ground state. The phenoxyl radical complexes have been generated in situ by the oxidation of phenolato complexes 1- 5 with (NH4)2[CeIV(N03)6] in CH3CN at 0 °C. The superoxide dismutase activity was examined by xanthine/xanthine oxidase nitroblue tetrazolium assay and DNA binding studies were investigated by absorption, fluorescence spectral measurements and circular dichroism. These complexes exhibited nuclease activity and the mechanism ofDNA cleavage was investigated. In chapter three of this thesis the coordination chemistry of zinc with the same tridentate ligand PhimpH (described in chapter 2) were discussed. Ligand PhimpH got coordinated to Zn(II) centre after deprotonation affording novel diphenoxo-bridged dinuclear zinc complexes [Zn2(Phimp)2(C104)2] (1) and [Zn2(Phimp)2(Cl)2] (2) [Zn2(Phimp)2(SCN)2] (3) and [Zn2(Phimp)2(N3)2] (4) and were characterized by IR, UVvisible, elemental analysis, NMR and conductivity measurements. Molecular structure of 2*CH2C12 was determined by X-ray crystallography and revealed some unique structural features. The complexes 1-4 showed emission properties upon excitation with UV irradiation and quantum yield for the complexes were determined with coumarine-land solvatochromism was also investigated. The phenoxyl radical complexes were generated at room temperature in CH3CN solution by adding (NH4)2[CeIV(N03)6] and were characterized by UV-vis and EPR spectral studies. DNA binding studies of these complexes were investigated by absorption spectral, fluorescence quenching and circular dichroism spectral studies. The phenoxyl radical complexes generated at room temperature exhibited nuclease activity with pBR322 DNA and mechanism was also investigated. Phenoxyl radical complexes were generated in copper and zinc complexes derived from ligand PhimpH and were described in chapter 2 and chapter 3. However, the ligand is devoid of any radical stabilizing group. Hence in chapter four of thesis new ligand tBuPhimpH ((E)-2,4-di-tert-butyl-6-((phenyl(pyridin-2-yl)hydrazono)methyl)phenol) was synthesized and characterized by UV-visible, IR, and NMR spectral studies. Copper as well as zinc complexes of tBuPhimpH ligand [Cu(tBuPhimp)(Cl)] (1) and [Zn(tBuPhimp)2] (2) were synthesized and characterized by IR, UV-visible, and NMR spectral studies and elemental analysis, ESI-MS data and conductivity measurements. Molecular structure of [Cu(tBuPhimp)(Cl)]-CH3OH (l-CH3OH) determined by X-ray crystallography. Investigation of photophysical property afforded that complex 2 showed emission properties upon excitation with UV irradiation. Electrochemical studies depicted Cu(II)/Cu(I) couple near - 0.80 V and a reversible peak for phenoxyl radical complexes of 1 and 2 in the range +0.8 to +1.0 V vs. Ag/AgCl were also scrutinized. The phenoxyl radical complexes were generated in CH3CN solution by adding (NH4)2[CeIV(N03)6] and characterized by UV-vis and EPR spectral studies. The stabilization of the phenoxyl radical complex 1 was compared with complexes [Cu(Phimp)(H20)]2(C104)2, [Cu(Phimp)2] and [Cu(Phimp)(L)] where L are CH3COO", SOT or N02~described in chapter 2. Moreover the same comparison was made between complex 2 and [Zn2(Phimp)2(L)2] where L = CF, SCN~, N3~ described in chapter 3. DNA binding studies of these complexes (1 and 2) were investigated by absorption spectral vi and fluorescence quenching spectral studies. Nuclease activity of the phenoxyl radical complexes was examined and mechanism was also investigated. In chapter five of thesis deals with copper(II) complexes 1- 6 of new tridentate ligand Pyimpy (Pyimpy = 1-phenyl-l-(pyridin-2-yl)-2-(pyridin-2-ylmethylene) hydrazine) were synthesized and characterized by elemental analysis, conductivity measurements, electronic absorption and IR spectroscopy. These data clearly expressed the formation of complexes [Cu(Pyimpy)(H20)](C104)2(l), [Cu(Pyimpy)2](C104)2 (2), [Cu(Pyimpy)(Cl)2]-2H20 (3-2H20), [Cu(Pyimpy)(N3)(C104)]2 (4), [Cu(Pyimpy)(SCN)(C104)]2 (5) and [Cu(Pyimpy)(Cl)(C104)] (6). Molecular structures of four complexes namely 2.C6H5CH3, 3-2H20, 4 and 6 were determined by single crystal X-ray diffraction. The stereochemistry around metal centers in 3-2H20 and 6 is described as distorted square-pyramidal and complex 4 was a centrosymmetric dimeric copper complex having two copper centers bridged with two azide ions in end-on fashion. Variable temperature magnetic susceptibility measurement showed intramolecular and very weak antiferromegnetic interaction in 4. The ligand binding to the copper centre was also supported by EPR spectral studies and stabilization of copper (II) centre was examined by electrochemical studies. The complexes 1 and 3 afforded superoxide dismutase (SOD) activity by xanthine/xanthine oxidase nitroblue tetrazolium assay. DNA interaction studies were investigated by absorption spectral studies, covalent binding assay, ethedium bromide displacement assay and circular dichroism spectral studies. All the complexes cleaved pBR322DNA oxidatively however, 6 showed oxidative cleavage as well as nuclease activity via self-activation. Complexes 1- 6 exhibited more cytotoxicity for MCF-7, PC-3 and HEK-293 cells as compared to CuCl2-2H20 and ligand Pyimpy. All the complexes 1- 6 showed more potency than cisplatin for MCF-7, PC-3 and HEK-293 cells. In chapter six of thesis deals with a new family of mononuclear Zn(II) complexes were synthesized using designed tridentate ligand Pyimpy (described in chapter 5) having NNN donors. The complexes were characterized by elemental analysis, UV-visible, IR and NMR spectral studies and conductivity measurements. These data suggested the formulation of [Zn(Pyimpy)2](C104)2 (1), [Zn(Pyimpy)(Cl)2] (2), [Zn(Pyimpy)(SCN)2] (3) and [Zn(Pyimpy)(N3)2] (4) for the new complexes described in this chapter. Molecular structures of l-C6H5CH3-0.5H2O and 2CH3CN were determined by X-ray crystallography. These vn complexes (1-4) also afforded strong fluorescent emission at room temperature in toluene. We investigated the DNA binding properties of these complexes by absorption spectral, fluorescence quenching and circular dichroism spectral studies. Nuclease activity was also examined and results were compared with the data obtained from corresponding copper complexes described in chapter 5. In chapter seven two new ligands Timpy (l,2-bis((E)-(2-phenyl-2-(pyridine-2- yl)hydrazono)methyl)benzene) and Gimpy ((lZ,2Z)-l,2-bis(2-phenyl-2-(pyridine-2- yl)hydrazono)ethane) and were synthesized and characterized by UV-visible, IR and NMR spectral studies. The ligands exhibited fluorescence spectra upon UV irradiation. This chapter deals with copper(II) complexes derived from tetradentate ligands Timpy and Gimpy and were characterized by elemental analysis, conductivity measurements, electronic absorption and IR spectroscopy. Above data supported the formulation of [Cu(Timpy)(C104)](C104) (1) and [Cu(Gimpy)](C104)2 (2). Molecular structure of 1 was determined by single crystal X-ray diffraction. The ligand binding to the copper centre was also supported by EPR spectral studies and stabilization of copper (II) centre was examined by electrochemical studies. DNA interaction studies were investigated by absorption spectral studies and ethedium bromide displacement assay. Both the complexes cleaved pBR322 DNA in absence of any oxidizing or reducing agents. The mechanism of DNA cleavage was investigated and two more examples of copper complexes were found to exhibit nuclease activity via self activation.