Synthesis, DNA Binding And Proliferation Inhibition Activities Of Transition Metal Complexes With Schiff Bases Containing 2-aminomethylbenzimidazole Or Valine

The interactions of metal complexes with DNA have been widely studied in the field of life science during the past decades for their potential utilities in the development of novel DNA structure probe and anticancer agents. Schiff base and its transitional complexes have received considerable attention due to the wide variety of biological activities such as antibacterial and anticancer. Benzimidazole nucleus, which is found in a variety of naturally occurring compounds such as vitamin B₁₂, is the pharmacophore of many kinds of medicines; natural ammo acids are indispensable nutrients for the human body. Schiff base and its complexes based on benzimidazole or amino acids may have higher biological activity. In order to screening high efficient, low toxic anticancer drugs, design, synthesis and DNA (or BSA) binding studies of binary or ternary transitional metal complexes with Schiff bases containing 2-aminomethylbenzimidazole or valine are disccused in this paper.The main work are as following:1. Three benzimidazole Schiff bases, N-(benzimidazol-2-ylmethyl)-salicylideneimine (HL¹), N-(benzimidazol-2-ylmethyl)-5-chloro-salicylidene imine (HL²), N-(benzimidazol -2-ylmethyl)-o-vallineneimine (HL³), have been synthesized. They were characterized by elemental analysis, IR, UV-Vis and ¹H NMR spectra. HL² was further determined by X-ray single crystal diffraction. The interaction between the compounds and DNA was studied by means of UV-Vis spectra, fluorescence spectra and viscometric titration. The compoundsbond to DNA in the same mode of partial interaction because of their similarity in structure. The binding ability followed the trend from high to low: HL² HL³ and HL¹. Moreover, their proliferation inhibition activities against human cancer human cancer cell lines colon carcinoma COLO205 and breast carcinoma MCF-7 were determined by MTT method.2. Ten transition complexes containing ligand of HL¹ and HL² have been synthesized. Their structure were characterized by means of elemental analysis, molar conductance, IR, UV-Vis and ¹HNMR and confirmed to be [M(L¹)Cl(H₂O)] or [M(L²)Cl(H₂O)], M = Cu(â…¡), Zn(â…¡), Co(â…¡), Ni(â…¡), Cd(â…¡). The binding studies of the copper and zinc complexes with DNA were carried out by means of UV-visible spectra, fluorescence spectra and viscometric titration. The results showed that the complexes could bind to DNA in the same mode. The binding abilities of the complexes were noticeable stronger than their own ligands. These may be attributed to the extension of the planar area of the intercalated ligand due to the coordination of M (â…¡), which leads to the coordinated ligand penetrating more deeply into and stacking more strongly with the base pairs of the DNA. Moreover, the potential inhibition activities of [Cu(L²)Cl(H₂O)]·H₂O against human cancer cell lines colon carcinoma COLO205 and breast carcinoma MCF-7 were determined by MTT method. The cytotoxity of the Schiff base was greatly improved by the formation of the complex with copper ion.3. Two copper ternary complexes of N-salicylidene-DL-valinato Schiff base (salval) with 1,10-phenanthroline (phen) and 2,2'-bipyridine (bpy) have been synthesized. Their structure were conformed to be [Cu(salval)(phen)] and [Cu(salval)(bpy)]·3H₂O via elemental analysis, molar conductance, IR, UV and TG-DTG. The single crystal of [Cu(salval)(bpy)]·3H₂O was cultivated and determined by X-ray crystallography. The binding reaction between the complexes and bovine serum albumin (BSA) was studied by fluorescence spectroscopy. The research results indicated that the two complexes had a quite strong ability to quench the fluorescence from BSA and their combmation reactions were mainly a static quenching process.