Interaction of zinc ( II ) and copper ( II ) terpyridine complexes with biomolecules

The kinetics and mechanism of the substitution reactions of dichloro [ZnCl2(terpy)] and [CuCl2(terpy)] (terpy = 2,2′:6′,2′′-terpyridine) with biologically relevant ligands have been investigated as a function of nucleophile concentrations at pH 7.38, under pseudo-first-order condition, by UV-Vis spectrophotometric techniques. The interactions of Cu(II) and Zn(II) complexes with tripeptide glutathione (GSH) were investigated under pseudo-first-order conditions with respect to the complex concentration. For the substitution process of Zn(II) complex with glutathione (GSH) pre-equilibrium and chelate formation have been noted. The [CuCl2(terpy)] is more reactive then [ZnCl2(terpy)] complex. The secondorder rate constants for the first step follow the order of reactivity: GSH > DL-Asp > L -Met > 5’-GMP ~ 5’-IMP for Cu(II) complex, while for Zn(II) the order of reactivity is: DL-Asp > L -Met > GSH ~ 5’-GMP > 5’-IMP.


Introduction
Transition metal compounds play crucial role as a cofactor in metalloproteins [1].They have unique role in diverse biological activities.Two essential metal ions zinc and copper have important role in enzyme activity, catalytic, regulatory function, oxidative-reductive processes and etc [1].
Biometal ions exist in single oxidation states such as zinc(II), which plays important role as a structural element in zinc-fingers, hydrolases, peptidases, important role as a structural element in zinc-fingers, hydrolases, peptidases, anhydrases, in gene regulation, etc [1].
As a catalytic cofactor Cu(II) is required in metalloproteins, plays important role in biological oxidation-reduction reactions, in electron transfer, because exists in multiple oxidation states Cu(II)/Cu(I) [1].
Zinc proteins are involved in control of the nucleic acid replication, transcription and repair, are implicated in many diseases and health complications because of that are recognized as medicinal target [2].
The anticancer drug cisplatin, cis-

Zinc-finger-DNA complex
Cu(II) as active centre is present in Cu/Zn-superoxide dismutase (SOD1) located in cytoplasm and mitochondria.SOD1 has antioxidant defence function, in regard to free radical detoxification [6].
Copper, also, has importance in cancer development and progression and serves as a limiting factor for multiple aspects of tumour progression, growth, angiogenesis and metastasis [6].
Our aim of work is to investigate the mechanism of interaction between zinc(II) and copper(II) complexes and biomolecules in proteins environmental.
The kinetics studies under physiological conditions were performed to provide more  biomolecules concentration.

Results and discussion
The so-obtained pseudo-first order rate constants, k obsd1 and k obsd2 , calculated from the kinetic traces (absorbance/time traces) were plotted versus the concentrations of the entering nucleophiles.
A linear dependence on the biomolecule concentration was biomolecule concentration was observed for the reactions with DNA constituent (5'-IMP and 5'-GMP) and amino acids (L-Met and DL-Asp).For the substitution reactions between [ZnCl 2 (terpy)] and glutathione first-order linear dependence, k obsd1 , on the complex concentration, at low concentration was observed.At higher concentration saturation kinetics was obtained.
Fast pre-equilibrium formation of intermediate, pseudo-octahedral complex, was observed, followed by rearrangement to was observed, followed by rearrangement to final complex whereas one chloride is substituted by GSH.
For the reactions between [CuCl 2 (terpy)] and glutathione linear dependence on the complex concentration was observed for the both reaction steps.
The substitution reactions include two reactions steps both mostly depend on biomolecules concentration.
The π-acceptor properties of the tridentate N-donor chelate (terpy) predominantly control the overall reaction pattern.
The different mechanisms of interactions of the pentacoordinate complexes with 5'-GMP, 5'-IMP and GSH have been obtained.
PtCl 2 (NH 3 ) 2 ], cis-DDP releases Zn(II) from the zinc coordination domain of the zinc coordination domain of polymerase-α isolated from prostate cells (PA3) and inhibits the replication process [3].The regulation of zinc-finger transcription factors has been shown by treatment of gene expression profiles of cell with cisplatin [4,5].