STUDIES ON NEW TRANSITION METAL COMPLEXES AND THEIR REACTIVITIES

Abstract

The thesis entitled “Studies on new transition metal complexes and their reactivities” is divided into seven chapters. In this report, we have presented rationally designed compartmental ligands which were utilized for the synthesis of mononuclear, dinuclear and tetranuclear metal complexes based on first-row transition elements viz. manganese, iron, nickel, copper and zinc. The chemical drawings of ligands utilized in this thesis are shown below in Figure 1. Figure 1 Chemical drawings of ligands utilized in the present thesis report. Chapter 1: Introduction This chapter includes the brief introduction of basic aspects of coordination chemistry including different metal ions and ligand employed in the thesis report. The introduction of several metalloenzymes, catalytic reactions and biomimetic reactivity studies were discussed. The various chemical methods and spectroscopic techniques used were comprehensively summarized in this chapter. The role of metal ions in association with rationally designed ligand frame in exhibiting different type of catalytic activities. R = -CH3, HLMe -OCH3, HLOMe -C(CH3)3, HLtBu LNN Thesis Abstract v Chapter 2: Dinuclear μ-phenoxo and μ-hydroxo bridged compartmental copper complexes exhibiting broad spectrum applications in oxidation chemistry of phenols and isoelectronic compounds: Cytotoxicity and evidences for cellular apoptosis In this chapter three compartmental pentadentate ligands HLMe, HLOMe, HLtBu have been synthesized, characterized and utilized for the synthesis of three dinuclear hydroxo and phenolato bridged copper complexes viz. [Cu2(LMe)(μ-OPh)(μ-OH](ClO4)2]CH3CN; (1), [Cu2(LOMe)(μ-OPh)(μ-OH)(μ-OH2)](ClO4)2.CH3CN; (2) and [Cu2(LtBu)(μ-OPh)(μ- OH)(OH2)](ClO4)2; (3) respectively. All the three complexes were characterized by various spectroscopic techniques. Tyrosinase activity was studied by in situ reaction of Cu(I) and ligands exploiting 2,4-di-tert-butyl phenol as substrate leading to radical mediated C-C coupling reaction. The catalytic activities of complexes 1-3 on di-phenols and related substrate molecules were investigated and all three complexes efficiently oxidize 3,5-di-tertbutylcatechol to 3,5-di-tert-butylquinone. Treatment of copper complexes on o-aminophenol and o-phenylene diamine resulted in the oxidative coupling of substrate molecules, leading to the formation of phenoxazinone and diaminophenazine respectively. Furthermore, oxidative properties of reported copper complexes were studied in relevance to their ability in inducing apoptotic cell death. Remarkably, all three copper complexes (1, 2 and 3) exhibited excellent cytotoxic activity towards MCF-7 cell lines (human breast cancer cell lines) with IC50 values of 1.6 μM, 2.0 μM and 0.2 μM respectively Self-activated DNA cleavage Cellular apoptosis Thesis Abstract vi Chapter 3: Facile synthesis and crystal structure of phenoxyl radical complex of zinc: Synthesis of benzoxazole derivatives by C-H bond activation via hydrogen atom transfer (HAT) and oxidation of dihydroanthracene In this chapter a tetranuclear zinc complex [Zn4(LOMe)2(μ2-OPh)2(μ3-OH)2(μ2- OAc)2](ClO4)3.2CH3CN (4) and a dinuclear diphenolato bridged complex [Zn2(LOMe)2(μ2- OPh)2](ClO4)2.2H2O (5) have been synthesized from compartmental ligand HLOMe (4- methoxy-2,6-bis(-(2-phenyl-2-(pyridine-2yl)hydrazono)methyl)phenol) using zinc acetate (Zn(OAc)2).2H2O) and zinc perchlorate (Zn(ClO4)2.6H2O) as precursor salts respectively. Complexes 4 and 5 were characterized by spectroscopic studies and molecular structures were determined by X-ray crystallography. Presence of phenoxyl radical in the solid state of complex 4 was authenticated by single-crystal X-ray diffraction, EPR, resonance Raman, and UV-Vis spectral studies. Theoretical calculations were performed to investigate structural parameters, spin density and resonance Raman spectral data. Redox properties of the complexes were examined. Stable zinc phenoxyl radical complex 4 derived from compartmental ligand served as a functional mimic of galactose oxidase enzyme. The hydrogen atom abstracting tendency of phenoxyl radical complex was supported by hydrogen atom transfer (HAT) reaction of 9,10-dihydroanthracene via C-H activation and synthesis of anthracene. This has been exploited for oxidative cyclization of Schiff base derivatives leading to the formation of benzoxazole derivatives via C-H bond activation under very mild conditions. Zn1 Zn2 Zn4 Zn3 O13 O16 H16 N1 N3 N4 N6 C18 O14 O15 N12 N10 N9 N7 O17 O20 H20 O18 O19 O21 O22 C51 Thesis Abstract vii Chapter 4: Combined experimental and theoretical studies on selective sensing of zinc and pyrophosphate ions by rational designing of compartmental chemosensor probe: Dual sensing behaviour via secondary recognition approach and cell imaging studies In this chapter ligand HLMe has been used as selective chemosensor probe for the selective recognition of zinc ions over other transition metal ions via fluorescence “ON” strategy. The chemo-sensing behaviour of HLMe has been demonstrated through fluorescence, absorption and NMR spectroscopic techniques. The molecular structure of the zinc complex [Zn2(LMe)2(μ2-OPh)2](ClO4)2.2H2O (6) derived from HLMe was determined by X-ray crystallography. A probable mechanism of this selective sensing behavior was described on the basis of spectroscopic results and theoretical studies by density functional theory (DFT). The biological applicability of the chemosensor (HLMe) was examined via cell imaging on HeLa cells. This zinc complex served as secondary fluorescent probe responding for the pyrophosphate anion specifically over other anions. The fluorescence enhancement of HLMe in association with Zn2+ ions was quenched due to the presence of pyrophosphate (PPi). Thus a dual response has been established based on “OFF-ON-OFF” strategy for detection of both cation and anion. This phenomenon was utilized in the construction of “INHIBIT” logic gate. Zn2+ PPi 450 500 550 600 650 700 0 20 40 60 80 100 120 Fluorescence Intensity (a.u.) Wavelength(nm) HL+Zn HL HL+Zn+ PPi (Ba2+) (Co2+) (Mn2+) (Fe3+) (Lig) (Zn2+) (Na+) (Cu2+) (Hg2+) (Mg2+) (Cd2+) Thesis Abstract viii Chapter 5: Study of cytotoxic activity of mononuclear Fe(II) and Mn(II) complexes based on bidentate ligands: Metal ions controlling catalytic performance towards SOD activity and nuclease activity In this chapter, mononuclear iron(II) and manganese(II) complexes [Fe(LNN)3](ClO4)2, (7) and [Mn(LNN)3](ClO4)2, (8) derived from bidenate ligand LNN, have been synthesised and characterized by various spectroscopic techniques. The X-ray crystal structures of the complexes revealed the tris coordination of three ligand moieties around metal centres providing distorted octahedral coordination environment. The SOD activity of both complexes was evaluated by following Xanthine/Xanthine oxidase assay. Complex 8 manifested efficient SOD activity with an IC50 values of 1.72 μM in contrast to the low-spin iron(II) complex which showed some anomalous behaviour. DNA cleavage activity through gel electrophoretic studies using pUC18 DNA were also studied revealing self activated DNA cleavage activity of 7. The cytotoxic nature of both complexes was determined on MCF−7 cell line. Complex 7 proved to be highly efficient in inducing nuclear deformation, promoting the apoptosis in the cells having IC50 value of 2.97 μM while complex 8 did not show cytotoxic activity. In situ reactive oxygen species generation has been further supported via DPPH (2,2-diphenyl-1-picrylhydrazine) radical quenching studies and DCFDA images. 1 2 3 4 5 6 7 lane Cleavage of supercoiled pUC18 plasmid DNA at 37 C (100 ng) by complex 2 using 2% DMF as a medium after incubation at 37 C for 30 min. DNA control (lane 1); DNA + Mn(ClO4)2.4H2O (lane 2); DNA + 2 (2μM) (lane 3); DNA + 2 (10μM) (lane 4); DNA + 2 (20μM) (lane 5); DNA+ 2 (60μM) (lane 6); DNA+ 2 (100μM) (lane 7). Form II Form III Form I Form II Form III Form I 1 2 3 4 5 6 7 8 lane Cleavage of supercoiled pUC18 plasmid DNA at 37 C (100 ng) by complex 1 using 2% DMF as a medium after incubation at 37 C for 30 min. DNA control (lane 1); DNA + Fe(ClO4)2.xH2O (lane 2); DNA + ligand (20μM) (lane 3); DNA + 1 (2μM) (lane 4); DNA + 1 (10μM) (lane 5); DNA + 1 (20μM) (lane 6); DNA+ 1 (40μM) (lane 7); DNA+ 1 (60μM) (lane 8). M = Fe, Mn 2+ Self-activated DNA cleavage Cellular apoptosis SOD activity 1 2 3 4 5 6 0 20 40 60 80 100 120 Concentration (M) % Inhibition 8 Thesis Abstract ix Chapter 6: Study of cytotoxic activity of mononuclear Fe(II) and Mn(II) complexes based on bidentate ligands: Metal ions controlling catalytic performance towards SOD activity and nuclease activity This chapter contains the report of synthesis and characterization of two nickel complexes [Ni2LMe(μ−Oph)(μ−OH2)(μ-NO3)(H2O)](NO3) (9) and [Ni4(LMe)2(μ−Oph)2 (μ− OH)2(μ-OAc)2](NaPF6) (10). Complex 9 is a dinuclear phenolato bridged, aqua bridged complex synthesized on employing nickel nitrate tetrahydrate as precursor metal salt while complex 10 was synthesized using nickel acetate as metal starting material. The characterizations of both complexes have been done by different spectroscopic methods like 1H NMR, IR spectra and UV-visible spectral studies along with X-ray crystallographic studies. Both complexes 9 and 10 were identified as paramagnetic complexes. The complexes were testified for the Suzuki-Miyaura reaction and both 9 and 10 were proved to be efficient cross-coupling agents under mild conditions and low catalyst loading for aryl iodide and phenyl boronic acid leading to carbon‒carbon bond formation which ultimately resulted in the synthesis of biphenyl. It is notable to mention here that no extra reducing agent was added to carry out the cross-coupling reaction. ⁺ Catalysts 100 C, THF, Base Iodobenzene Phenyl boronic acid Biaryl (biphenyl) Thesis Abstract x Chapter 7: Synthesis, characterization and reactivity studies on dinuclear manganese (II,II) and mononuclear iron(III) complexes This chapter reports the rational designing and synthesis of dinuclear diphenolato manganese complex [Mn2(LMe)2(μ−Oph)2](ClO4)2 (11) and mono nuclear bis-coordinated iron complex [Fe(LMe)2(μ− Oph)2](ClO4).2CH3OH (12) based on compartmental ligand HLMe. The characterization of both complexes was done by different spectroscopic methods such as IR spectral studies, UV‒visible spectroscopy, and electrochemical studies. Molecular structures of both complexes were determined by X‒ray crystallography. The oxidative capability of both complexes was investigated utilizing a range of substrates including hydrocarbons, alcohols and substituted thio ether. Both the complexes were found to be efficient as oxidation catalysts in presence of hydrogen peroxide. The generation of intermediate species were justified using UV-Vis spectroscopy and ESI-MS spectral analysis