SOME ASPECTS OF MANGANESE AND IRON CHEMISTRY WITH POLYDENTATE LIGANDS

Abstract

Coordination chemistry is an important branch of chemistry which deals with study of compounds formed between metal ions and ligands (neutral or negatively charged). Inorganic chemistry has several branches and bioinorganic chemistry is one of them. Bioinorganic chemistry describes the mutual relationship between inorganic chemistry and biochemistry. This basically deals with the role of inorganic substances such as metal ions, composite ions, coordination compounds or inorganic molecules inside the living organism. Role of bioinorganic chemistry is to understand all the possible interactions between these inorganic substances and the biological tissues. These interactions can only be studied with the knowledge of coordination chemistry where metal ions bind with the ligands which could be the side chain of amino acid or any other biomolecule. Hence bioinorganic chemistry goes hand in hand with the coordination chemistry. These understandings could be further utilized for the advancement of several fields such as medicinal chemistry, biochemistry, environmental chemistry, chemistry of catalysis and metallopharmaceutical research. Transition metals have been a part of active site in various enzymes due to several bases such as stability in variety of geometries, multiple coordination site, stability in variety of oxidation state and capability of stabilizing intermediates in several processes. A significant aim of bioinorganic chemistry is to design small inorganic coordination complexes which have similar structural features and also function in a manner similar to their natural ones. The synthetic approach mainly deals with the active site and its coordination environment. Manganese and iron both the metals are found in the active site of native enzymes but these molecules as such cannot be utilized as pharmaceutical agents. These metals have been used widely for structural, functional or structuralfunctional mimicking of these metal enzymes. In this regard complexes which are cheap, low molecular weight, less toxic and having good iv solubility in water are highly demanding. Moreover, manganese and iron complexes have been utilized for various medicinal applications. In continuation of the importance of these metals, design and synthesis of fluorescent probes selective and sensitive for monitoring heavy and transition metal ions is a demanding and promising area of research because of the prominent impact of metal ions in environment and biology. A remarkable development of small fluorescent molecule with selectivity towards metal ions has been dragged attention of researchers. These studies are found to be helpful to understand transport and localization as well as physiological and pathological effect of metal ions in the cell. Due to high sensitivity, rapid response and simplicity, fluorescence has attracted much attention for the detection of several chemical analytes in solution. Iron is an important transition metal found in biology exhibiting crucial roles in several catalytic and enzymatic reactions and its imbalance can cause harmful effects hemochromatosis, cancer etc. Hence detection of iron and its concentration as well as localizations are extremely important for the treatment of such diseases. The thesis entitled “Some Aspects of Manganese and Iron Chemistry with Polydentate Ligands” is divided into seven chapters. In present studies, we have designed novel bidentate and tridentate ligands having meridional geometry. Synthesized ligands were further subjected to characterization and data supports the proper synthesis of ligands. The ligands used in present investigation have been depicted in the Fig. 1. v Fig.1 Ligands utilized for the present studies. These ligands were utilized to synthesize mononuclear manganese and iron complexes. Complexes of manganese and iron were also characterized using various spectroscopic techniques. The representative complexes were subjected to X–ray crystallography to justify the molecular structure. Redox activities of all the complexes were optimized using electrochemical studies. First chapter presents an introduction to coordination chemistry of manganese and iron. In this chapter background of the present work along with literature review are described. The chemical systems reported in this thesis are deeply introduced in this chapter. The various chemical methods and equipments used are comprehensively summarized. vi In chapter two, tridentate ligands OCH3PhimpH, CH3PhimpH, tBuPhimpH and NO2PhimpH have been synthesized and characterized. The designed tridentate ligands having N2O donors upon deprotonation bind to iron(III) resulting in a series of novel iron complexes. All the complexes were characterized by elemental analysis, IR and UV–visible spectral studies. Spectroscopic data, magnetic moment and conductivity measurement clearly expressed the formation of [Fe(OCH3Phimp)2](ClO4) (1), [Fe(CH3Phimp)2](ClO4) (2), [Fe(tBuPhimp)2](ClO4) (3) and [Fe(NO2Phimp)2](ClO4) (4) complexes. Molecular structure of complex 1 was determined by single crystal X–ray diffraction study. A distorted octahedral geometry was observed having FeN4O2 coordination sphere. Molecular structure studies interpret tridentate meridional coordination of ligand around iron(III) metal centre. Electrochemical studies were also investigated for synthesized complexes. Theoretical calculation using DFT was also performed to optimize the geometrical and structural parameters. TD–DFT was also optimized to observe the electronic properties and data obtained was found to be consistent with that of experimentally obtained values. Complexes 1, 2, 3 and 4 utilized to optimize oxidation of o–aminophenol in methanol. Complexes were found to be efficient in the oxidation of o–aminophenol. Kinetic experiments were also explored to gain better insight into the oxidation process. Representative complex exhibited nuclease as well as protease activities in absence of external agents. Complex was found to cleave the DNA and protein via self activated mechanism. Chapter three tridentate ligands OCH3PhimpH, CH3PhimpH, and tBuPhimpH having N2O donors coordinates to manganese(III) after deprotonation affording a series of mononuclear manganese complexes. All the complexes were characterized by elemental analysis, IR and UV– visible spectral studies. Magnetic moments and conductivity measurements suggested the vii formulation of [Mn(OCH3Phimp)2]ClO4 (5), [Mn(CH3Phimp)2]ClO4 (6) and [Mn(tBuPhimp)2]ClO4 (7) manganese complexes respectively. Molecular structure of 7 was determined by X–ray crystallography and structural features were also explored. Cyclic voltammetric studies were also monitored for all the complexes in the series. DFT calculations were also monitored for representative metal complex to optimize geometrical and structural parameters. TD–DFT studies explained the electronic properties and are in good agreement with those of experimentally obtained. The phenoxyl radical complexes were generated at room temperature in CH3CN solution by adding [(NH4)2[CeIV(NO3)6] and were characterized by UV–visible spectral studies. The phenoxyl radical complex generated at room temperature exhibited nuclease as well as protease activity with pBR322 DNA without any external agent. In chapter four, two novel ligands H–N3L (1–phenyl–1–(pyridine–2–ylmethyl)–2– (pyridine–2–ylmethylene)hydrazine) and Me–N3L (1–phenyl–2–(1–(pyridin–2–yl)ethylidene)– 1–(pyridin–2–ylmethyl)hydrazine) have been designed and synthesized. These ligands have been characterized using various spectroscopic techniques such as UV–visible, IR, GC–MS and NMR spectral studies. Synthesized ligands have been utilized to prepare mononuclear complexes of manganese. A series of manganese complexes [Mn(H–N3L)Cl2] (8), [Mn(H–N3L)2](ClO4)2 (9), Mn(Me–N3L)Cl2 (10) and [Mn(Me–N3L)2](ClO4)2 (11) were synthesized and characterized by spectroscopic techniques. Molecular structure of complex 10.CH3COCH3 was determined by single crystal X–ray diffraction technique. Molecular structures interpret distorted octahedral geometry and tridentate meridional coordination of ligand around manganese. Redox properties were also explored for the synthesized metal complexes. Theoretical calculations were also performed using complex 10 and the geometrical and structural parameters were also viii investigated. TD–DFT calculations justify the electronic properties obtained from the experimentally obtained values. The complexes 8, 9, 10 and 11 were employed to catalyze the dismutation of superoxide using xanthine–xanthine oxidase–nitroblue tetrazolium assay and obtained good IC50 values. DNA interaction studies were also monitored using all complexes. Nuclease as well as protease activity exhibited in presence of oxidising agent for the representative complex. In chapter five, tridentate ligands H–N3L (1–phenyl–1–(pyridine–2–ylmethyl)–2– (pyridine–2–ylmethylene)hydrazine) and Me–N3L (1–phenyl–2–(1–(pyridin–2–yl)ethylidene)– 1–(pyridin–2–ylmethyl)hydrazine) have been utilized to synthesized mononuclear iron complexes. Complexes [H–Fe(N3L)Cl3] (12) [H–Fe(N3L)2](ClO4)2 (13) [Fe(Me–N3L)Cl3] (14) and [Fe(Me–N3L)2](ClO4)2 (15) have been synthesized and characterized using elemental analysis, IR, UV–visible and ESI–MS spectral studies. Magnetic moment and conductivity measurements also supported the formulated structures of the complexes. NMR spectral studies were also performed for complexes 13 and 15 due to the presence of low spin Fe(II) metal centre. Structural and geometrical aspects were monitored using DFT calculations. TD–DFT calculations were also performed to optimize the electronic properties and found to be in good agreement with the experiment one. Electrochemical studies were also investigated for all the complexes in the series. Due to the stability in buffer these complexes were subjected to the DNA interaction studies. DNA binding studies were monitored using UV–visible, fluorescence and CD spectral studies. These studies indicated that all the complexes bind well with the DNA. Nuclease activity was also monitored for the representative complexes and exhibited oxidative DNA nuclease in presence of oxidizing agent (H2O2). ix In chapter six, a naphthylamine based probe NED1 (N–(2–aminoethyl)naphthalen–1– amine) was utilized for the detection of Hg(II), Fe(II), Fe(III) in mixed aqueous media via fluorescence quenching. These sensitive metal ions bind with the probe by forming a 1:1 complex. Time resolved fluorescence and quantum yield of probe NED1 in absence as well as in presence of metal ions were investigated. Extent of binding of probe with sensitive metal ions was calculated. Sensitivity of the probe in presence of other metal ions was examined using competitive binding studies. Probe NED1 displayed sensitivity towards Hg(II) during in vitro as well as in vivo studies. This multianalyte probe demands biological applications in cell imaging and in logic gates. Chapter seven presents the synthesis a novel fluorescent probe NED2 (2–((2– (naphthalen–1–ylamino)ethylimino)methyl)phenol) has been synthesized via a simple one step synthetic procedure and characterized by various spectroscopic methods. Photo–physical properties of NED2 have been investigated to study the sensing of metal ions in methanolic solution. Probe NED2 was found to be highly selective for iron over tested metal ions. Probe NED2 selectively detected iron in both +2 and +3 oxidation states giving rise to yellow–brown and purple color respectively. The naked eye detection of iron is useful for the discrimination of +2 and +3 oxidation state while fluorescence studies concludes selective and specific sensitivity towards Fe(III). Probe NED2 was found to be highly sensitive and selective towards Fe(III) during fluorimetric detection. Binding stoichiometry was found to be 1:1 for Fe(III) and probe NED2. DFT calculation provided that the decrease in the energy gap between HOMO and LUMO is probably responsible for the quenching of fluorescence. Logic gates application of the probe NED2 was also explored. x The material, reagents synthetic procedure and experimental details for complexes will be described in the respective chapters. The thesis concludes with a few suggestions for further work.