Studies on transition metal complexes of flexible polydentate schiff base ligands

Abstract

Utility of transition metal complexes in different sphere of life is one of the pertinent research field which has been extensively explored since the time of Werner who has put forward his theory to understand the structure and bonding for this class of compound. Inorganic chemists have also taken clue from the natural phenomena where transition metal complexes have been widely used in several biological processes, to understand the underlying principles of functionality, which eventually helps to develop different structural and more importantly improved functional model systems. The role of different ligand systems to bring out the necessary function has been gradually understood and different kind of ligand systems have been experimented to obtain better results. Schiff base ligands have shown remarkable advantages to stabilize the transition metal complexes which could be advantageous to generate a robust system with effective applications. With the time it has been perceived that metal complexes can be useful not only in biological processes but it can play crucial role in developing new materials and chemicals with diverse propertiesWith the aim of development of improved Schiff-base ligands for effective application, introduction of flexibility of the ligands have been explored which paved the way of remarkable adaptability in the metal complex which can be utilized to tune it effectively as per desired properties. However, this type ofstudy has not been explored so far exhaustively and there are ample opportunities to look further into it for the better effectiveness of these kind of systems in terms of applicability. Although there are large scope of applications of metallo-Schiff base complexes which grasps wide and differentiated subjects containing immense territories of coordination chemistry, but this thesis mainly deals with the structure-activity relationship between flexibility of Schiff bases in metal complexes and certain special properties with an emphasis onDNA / Protein binding and cleavage property: which is a key research field to develop new therapeutic metallodrug. (ii) Antiproliferative property: for damaging the cancer cell lines. (iii) Antimicrobial activity: a new way to inhibit the growth of microorganisms like bacteria, fungi, etc. (iv) Catecholase activity: where the polymerization of the oxidized product affords the formation of melanin, which protects damaged tissues against pathogens or insects. (v) Glycosidase activity: Which catalyze the hydrolysis of glycosidic linkages to mimic the natural enzyme which is prevalent in carbohydrate metabolism. (vi) Corrosion inhibition property: protects the damage of mild steel which is an essential constructing element in various industries. With the above scenario the primary objective of the research work reported in this thesis is:-  To explore the structure-activity relationship between several kinds of biological, chemical as well as material properties and various complex structures tuned by flexibility as well as flexibility controlled nuclearity. However, to achieve this primary objective, this work has been subdivided into certain tasks as follows :-  To design and synthesize Schiff bases incorporating flexible organic moiety. To tune the flexibility by coordinating the ligand with different type of metal ions and using different metal ion precursor.  To take advantage of the co-ligands to generate polynuclear metal complexes and to control the nuclearity. On the basis of the above objectives the contents of each chapter included in the thesis are discussed briefly as follows: Chapter 1: General Introduction and Background A brief overview of the basic concepts and recent scientific developments towards the generation of Schiff base metal complexes and the importance of introducing the flexibility towards potential applications in various biological, chemical and material applications are discussed in this chapter. Finally, a brief summary of the research reported in this thesis and the relevance in the prospects of recent developments have been put forward. Chapter 2: Nickel(II) complexes with a flexible piperazinyl moiety: studies on DNA and protein binding and catecholase like properties In this chapter, four new mononuclear Ni(II) complexes [Ni(L1)]ClO4 (1), [Ni(L2)]ClO4 (2), [Ni(SCN)3(CH3OH)(aminoethyl-piperazineH)] (3), and [Ni(DMSO)4(aminoethylpiperazineH)](ClO4)3 (4) have been synthesized from two Schiff base ligands [HL1 = 1-phenyl-3-((2-(piperidin-4-yl)ethyl)imino)but-1-en-1-ol and HL2 = 4-((2-(pipera-zin-1-yl)ethyl)imino)pent-2-en-2-ol] by exploiting the flexibility of the piperazinyl moiety. Structural analysis reveals that 1 and 2 are square planar complexes with piperazine rings in boat conformation whereas hydrolysis of Schiff bases (HL1 and HL2) occurs during formation of octahedral complexes (3 and 4) with piperazine rings in chair conformation. Screening tests were conducted to quantify the binding ability of complexes towards DNA, BSA and HSA and it was found that square planar complexes (1 and 2) showed more effective binding properties over octahedral complexes as hydrolysis of Schiff bases during complexation restricts the delocalization of electrons to make these two complexes (3 and 4) inactive towards all kind of activity. Furthermore, enzyme kinetic studies reflect thatsquare planar complexes (1 and 2) are also effective in mimicking catecholase like activities over octahedral complexes. Among all the complexes, 1 was found to be the most promising molecule among the series due to its large binding affinity towards different biomacromolecules and higher turnover frequency in the catechol oxidation reaction. Chapter 3: Copper complexes with flexible piperazinyl arm: nuclearity driven catecholase activity and interactions with biomolecules In chapter 2 efforts were made to synthesize Schiff Base complex with chair conformation however in all such cases the Schiff Base ligand gets hydrolyzed to precursor amine. In this chapter it was aimed to check the flexibility of the ligand upon reaction with other metal center. Exploration of the reactivity with copper ion produced three new Cu(II) complexes viz., [Cu(HL1)(Pyridine)(H2O)](ClO4)2.2MeOH (5), [Cu2(HL1)2(NO3)2](NO3)2.3H2O (6) and [Cu(HL2)(NO3)2].MeCN (7) have been synthesized from those two Schiff base ligands where the flexible piperazinyl moiety takes up chair conformation. Structural analysis reveals that 5 and 7 are monomeric Cu(II) complex consisting of penta- and hexacoordinated Cu(II) centers, respectively, whereas 6 is a dinuclear Cu(II) complex with two different geometrical Cu(II) centers, one is square planar and the other is distorted octahedral. Screening tests were conducted to quantify the binding ability of complexes (5, 6 and 7) towards DNA and BSA as well as the DNA cleavage activity have been explored of these complexes using gel electrophoresis technique. Furthermore, enzyme kinetic studies are also performed for those three complexes towards effectiveness in mimicking of catecholase like activities. Antibacterial activities of these complexes are also scrutinized towards Methicillin-Resistant Staphylococcus aureus (MRSA) bacteria. Finally, the nuclearity driven activity of complex 6 towards DNA binding and catechol oxidations are further explained by DFT.Chapter 4: Nickel(II) and copper(II) complexes constructed with flexible Schiff base ligand: Synthesis, X-ray crystal structure, enzyme catalysis and biological applications The flexibility of Schiff base ligands (HL1 and HL2) upon variation of different metal ions was explored in above two chapters but with changing reaction conditions or with variation of auxiliary anion with same metal has not produced any pair of complexes where the ligand is in two different conformation. For this reason a modified Schiff base ligand HL3 [2-(phenyl((2-(piperazin-1-yl)ethyl)imino)methyl)phenol] has been introduced. Structural features and different applications of four newly synthesized metal complexes formed by the reaction of this ligand HL3 with Cu(II) and Ni(II) salts are discussed in two parts. 4A - Investigation on chemical protease, nuclease and catecholase activity of copper(II) complexes with flexidentate Schiff base ligands This part mainly deals with two Cu(II) complexes [Cu(HL3)(MeOH)(Py)](ClO4)2 (8) and [Cu(HL3)(DMF)](NO3)2 (9). Crystallographic study reveals that like last chapter, here also the piperazinyl arm remains in chair form making the ligand effectively tridentate in nature leaving enough coordination position available for binding of the substrate. Affinity of the synthesized complexes towards BSA protein and DNA were carried out through binding and cleaving experiment which have been followed by cell cytotoxicity measurement. Possible catecholase like activity was also investigated. Interestingly both the complexes have shown interesting protease, nuclease and catecholase activity. 4B - Counter anion directed flexibility of Ni(II) Schiff base complexes: Lysozyme binding and glycosidase activity In this part of the thesis ligand HL3 was reacted with two different Ni(II) salts and finally structurally two different complexes [Ni(L3)(MeOH)] (ClO4)2 (10) and [Ni2(HL3)2(H2O)2(MeOH)2]Cl3.3MeOH (11) were synthesized. Among these two, the piperazinyl arm is in boat conformation in Ni(II) complex 10 and in chair conformation in Ni(II) complex 11 which is a chloro-bridged dimericmolecule. Probable reason behind this structural diversity by coordination mode of chloride ion is described here. Apart from a structural point of view, the lysozyme binding activities and glycosidase activities of these two complexes were also determined. The results confirm that nuclearity can play an important role in above mentioned activity. Chapter 5: A novel approach of pseudohalide promoted enhanced corrosion inhibition by antimicrobial zinc(II) Schiff base complexes This chapter describes the structure-activity relationship of corrosion inhibition property of Zn(II) Schiff base complexes which were prepared in a stepwise well planned synthetic approach. In this regard, two complexes ([Zn(L4)2](ClO4)2 (12) and [Zn(μ-fumarate)(L4)]n (13) derived from two ligands L4 [N1,N1-dimethyl-N2-(1-(pyridin-2-yl)ethylidene)ethane-1,2-diamine] and L5 [N1,N1-diethyl-N2-(1-(pyridin-2-yl)ethylidene)ethane-1,2-diamine] were synthesized and their detail electrochemical analyses reveal that the compounds are inert towards any anti-corrosion property like their parent organic ligand. Thus enhancement of hetero-atom availability via incorporation of azide as a co-ligand for greater adsorption of the molecules on the mild steel was planned and successful implementation of this idea produces four new Zn(II) complexes [ZnL4(N3)2] (14), [ZnL5(N3)2] (15), [ZnL6(N3)2] (16) and [ZnL7(N3)2] (17)) where, ligands L6 [2-morpholino-N-(1-(pyridin-2-yl)ethylidene)ethanamine] and L7 [(2-(piperidin-1-yl)-N-(1-(pyridin-2-yl)ethylidene)ethanamine)] contained flexible morpholinyl and piperadinyl moieties in their chair conformation. Electrochemical polarization and impedance studies indicate that all these four Zn(II) azido Schiff base complexes have significant corrosion inhibition property in 15% HCl medium on mild steel. FE-SEM (Field emission scanning electron microscopy) and AFM (Atomic force microscopy) images depicted that metal surface is protected by these four Zn(II) complexes. Apart from these, the antimicrobial activities of these complexes have been scrutinized. Considering all above facts, it can be concluded that this kind of pseudo halide promoted enhanced corrosion inhibition approach is one of thefruitful strategies to develop corrosion resistance metal complexes which are worth for further investigation. Chapter 6: Targeted synthesis of cadmium(II) Schiff base complexes towards corrosion inhibition on mild steel Being inspired by the results of the last chapter, this chapter is focused on the enhancement of the corrosion inhibion efficiency via incorporation of some robust metal ion such as cadmium as it is widely used as an electroplating element in aircraft for corrosion protection of airframe components. Thus, the reaction of cadmium salts with three ligands L4, L6 and L7 gave five Cd(II) Schiff base complexes [Cd(L4)2](ClO4)2 (18), [Cd(L4)(cyanoacetate)(OAc)] (19), [Cd2(L4)2(N3)4] (20), [Cd(L6)(N3)2]n (21), [Cd2(L7)2(N3)4]n (22). The corrosion inhibition property of these complexes on mild steel upon treatment with 15% HCl has been examined where azide complexes have shown significant corrosion inhibition property as revealed by electrochemical impedance spectroscopy and potentiodynamic polarization. FE-SEM images show that the mild steel surface was protected by cadmium complexes. Among azido complexes, polymeric complexes have higher inhibition activity (up to 94%) due to the more availability of hetero atoms which was further explained using density functional theory. Thus finally, it can be concluded that increasing adsorbing sites by increasing nuclearity could be one of the key factors to develop corrosion resistance polymeric metal complexes which are worth for further investigation.Chapter 7: General conclusions and future scope This chapter summarizes the salient features of the work and its future prospects.