STUDIES ON IRON AND MANGANESE COMPLEXES OF POLYDENTATE LIGANDS

Abstract

Metal ions bind to ligands on the basis of acid-base chemistry and stabilize variable oxidation states of metal. It is well known in the literature that the ligands having pyridine nitrogen, imidazole nitrogen and thioether stabilize the lower oxidation states of the metals. On the other hand, carboxylato oxygen, carboxamido nitrogen, phenolato oxygen stabilized the metals in higher oxidation state. Moreover a ligand can stabilize the low-spin or high-spin state of a metal ion in a particular oxidation state. Hence, a ligand imparts attractive properties to a metal ion by stabilizing the specific oxidation and spin states (low-spin or high-spin). Occasionally, metal ions could show interesting coordination geometries in presence of some ligands. These characteristic features could be exploited to study their reactivities. Manganese and iron are two important members among the first row transition elements. These two essential elements are not only important for bio-system but also their versatile coordination chemistry was often exploited in catalytic activity, synthesis of materials and medicinal chemistry etc. In present study, the designing of new ligands, their synthesis and characterization will be described. Manganese and iron complexes derived from those ligands and their spectroscopic and magnetic properties will be described. Molecular structures of ligands and representative metal complexes were determined by X-ray crystallography. The results of reactivities studies on manganese and iron complexes will be scrutinized in this thesis. The thesis is divided into the following chapters. First chapter presents a brief introduction to chemistry of manganese and iron and its importance in coordination chemistry with different type of ligands environment. Several manganese and iron containing metalloenzymes and their role in bio-system were discussed in this chapter. A review of available literature on iron and manganese complexes based on structural and functional mimicking of metalloenzymes and their application in different fields of bioinorganic chemistry have been discussed. The chemical systems report in this thesis is deeply introduced in this chapter. The various chemical methods and spectroscopic techniques used were comprehensively summarized in this chapter. Second chapter describes the manganese chemistry with a new family of tridentate ligands PhimpH (2-((2-phenyl-2-(pyridin-2-yl)hydazono)methyl)phenol), N-PhimpH (2-((2- iv phenyl-2-(pyridin-2-yl)hydrazono)methyl)napthalen-1 -ol), Me-PhimpH (2-(1-(2-phenyl-2- (pyridine-2-yl)hydrazono)ethyl)phenol) having phenolato donor, imine donor and pyridine donor were synthesized and characterized (NMR, GC-MS, IR, UV-vis). The synthesis and properties of a number of manganese(II) and manganese(III) complexes namely [Mn(Phimp)2] (1), [Mn(Phimp)2](C104) (2), [Mn(N-Phimp)2] (3), [Mn(N-Phimp)2](C104) (4) and [Mn(Me-Phimp)2](C104) (5) with these ligands are discussed, including the interconversion between the various manganese complexes. The molecular structures of 1 and 2 were determined by single crystal X-ray diffraction. Electrochemical studies for the all complexes (1-5) showed Mn(II)/Mn(III) and Mn(III)/Mn(IV) couples vs Ag/AgCl. The redox properties were exploited to examine superoxide dismutase (SOD) activity using Mn(II)/Mn(III) couple in complexes 1, 2, 4 and 5. DNA interaction and nuclease activity studies with selected complexes were performed and their mechanisms were discussed in this chapter. Third chapter deals the effect of metal properties with ligand having carboxamido nitrogen donor in place of imine nitrogen donor on SOD as well as nuclease activity. Forthis purposes a series of new tridentate ligands (Pyimpy (2-((2-phenyl-2-(pyridin-2- yl)hydazono)methyl)pyridine), Me-Pyimpy (1 -phenyl-1 -(pyridin-2-yl)-2-(1-(pyridin-2- yl)ethylidene)hydrazine) and PampH (N'-phenyl-N'-(pyridin-2-yl)picolinohydrazide)) having imine and carboxamido nitrogen donor were synthesized and characterized (NMR, GC-MS, IR, UV-vis). Hexa-coordinated mononuclear complexes [Mn(Pyimpy)2](C104)2 (1), [Mn(Me- Pyimpy)2](C104)2 (2), [Mn(Pamp)2](C104)CH3OH (3-CH3OH), [Mn(Pyimpy)(H20)Cl2] (4), [Mn(Me-Pyimpy)(H20)Cl2] (5) were synthesized and characterized. The molecular structures of 3CH3OH and 4 were determined by single crystal X-ray diffraction, which afforded distorted octahedral coordination sphere having meridionally spanning ligands. The redox properties were exploited to examine superoxide dismutase (SOD) activity using Mn(II)/Mn(III) redox couple. Complex 3 having ligands containing carboxamido (Nam) donor, has been revealed to catalyze more effectively the dismutation of superoxide (02 ) ions in xanthine-xanthine oxidase-nitro blue tetrazolium assay as compared to other complexes. Among all complexes (1-5), complex 3 was found to be most effective in nuclease activity in presence of H202. v Fourth chapter deals with synthesis of iron complexes derived from tridentate Schiff base ligands Pyimpy, Me-Pyimpy and ligand having peptide bond PampH. Complexes [Fe(Pyimpy)Cl3]-2CH2Cl2 (1-2CH2C12), [Fe(Me-Pyimpy)Cl3] (2), [Fe(Pyimpy)2](C104)2 (3) and [Fe(Me-Pyimpy)2](004)2 (4) were synthesized and characterized spectroscopically. Interestingly, complexes 1 and 2 spontaneously reduced (Fe(III)) and converted to complexes 3 and 4 (Fe(II)), their interconversion was monitored by UV-visible spectral studies. Lowspin nature of complexes 3 and 4 were confirmed by magnetic moment and NMR studies. In order to examine the role of carboxamido nitrogen on the metal centre, complexes [Fe(Pamp)(MeOH)Cl2] (5) and [Fe(Pamp)2](C104) (6) were also synthesized and characterized. Magnetic moment data indicate high-spin and low-spin nature of complexes 5 and 6 respectively. Molecular structures of 1-2CH2C12 and 6 were authenticated by X-ray crystallography. Redox properties of all metal complexes will be analyzed in detail. We explored DNA interaction studies of selected complexes and will investigate the role of carboxamido nitrogen in nuclease activities. Complexes 1 and 2 during spontaneously reduction (12 h-15 h) and interconversion are capable to cleave pBR322 plasmid without adding external reducing agents. The DNA cleaving ability of all complexes (1-6) were explored in presence or absence of oxidative or reducing agent. Fifth chapter demonstrated the iron chemistry with ligands PhimpH, Me-PhimpH and N-PhimpH. Complexes [Fe(Phimp)(H20)(OMe)Cl] (1), [Fe(Phimp)Cl2] (2), [FefMe- Phimp)Cl2] (3), [Fe(Me-Phimp)Cl2] (4), [Fe(Phimp)2](C104) (5), [Fe(Me- Phimp)2](N03)H20 (6H20) and [Fe(N-Phimp)2](C104) (7) were synthesized and characterized using different spectroscopic techniques eg. IR, UV-vis, magnetic moment, conductivity, X-ray crystallography. Iron centre was in +3 oxidation state in all complexes because of hard donor -0Ph (phenolato) in the ligand frame. Molecular structures of 1, 2, 4, 5 and 6H20 were authenticated by X-ray crystallography. DNA binding properties were investigated by UV-vis, fluorescence and circular dichroism techniques. All complexes were investigated for biochemical effects on DNA in vitro and on cultured human cells (MCF7) and show promising results. v; Sixth chapter describes the synthesis and characterization of new tetradentate ligand Gimp having imine and pyridine nitrogen donors. Iron complex [Fe(Gimp)Cl2], (1) and [Fe(Gimp)(CN)2]-3H20, (2-3H20) were synthesized and characterized by different spectroscopic studies. Reactivity of acidified nitrite solution gave rise to ligand nitration [Fe(Gimp-N02)(CN)2]CH2Cl2CH3OH, (3CH2C12CH30H) and formation of [Fe(Gimp)(NO)(CN)](C104), (4). To investigate the role of carboxamido nitrogen we designed another ligand (GampH2) having pyridine and carboxamido nitrogen donors. Complex [Fe2(Gamp)(DMF)2Cl4], (5) was synthesized and nitric oxide (NO) reactivity was examined. Low-spin nature of complexes 2 was confirmed by NMR spectral studies. Structures of complexes 2, 3CH2C12CH30H and 5 were established by X-ray crystallography. Weak antiferromagnetically nature of complex 5 was confirmed by SQUID measurements. Seventh chapter describes the synthesis and characterization of new pentadentate Schiff base ligand (N5L = 2,6-bis(l-(2-phenyl-2-(pyridin-2-yl)hydrazono)ethyl)pyridine). The corresponding novel seven coordinated manganese complex [Mn(N5L)(H20)(C104)](C104), 1 was synthesize and characterized by different spectroscopic technique. X-ray crystal structure of complex 1 confirmed the pentagonal-bipyramidal geometry of Mn(II) complex with one ligand (N5L), water and one perchlorate molecule at apical position. The electrochemical property of complex 1 was investigated by cyclic voltammetry (CV) measurements. This seven coordinated complex 1 was found to be capable in DNA strand cleavage of pBR322 plasmid with or without additives (H202 or 2- mercaptoehanol (BME)). The complex could be used as magnetic resonance imaging (MRI) contrast agent.