Aims: The study aimed at investigating interactions between zinc(II) complexes with different geometrical structures and relevant nitrogen donor nucleophiles at physiological pH.
Background: Lack of clear distinction between the therapeutic and toxic doses of platinum drugs is a major challenge for the design of novel non-platinum DNA and protein targeting metal-based anticancer agents. The non-platinum antitumor complexes could be alternatives to platinum-based drugs due to their better characteristics and different mechanisms of action.
Objective: This study could provide more information regarding the design of future zinc-based anticancer drugs, providing a better understanding of the mechanism of interactions between Zn(II) complexes and nitrogen-donor nucleophiles (important from the medical point of view), and clarifying the changes in geometrical structures of zinc(II) that are referred to structure-reactivity correlations.
Methods: Mole-ratio method and UV-V is spectroscopic kinetic method have been used.
Results: The results indicated additional coordination of chlorides in the first coordination sphere with changes in coordination geometry and formation of the octahedral complex anion [ZnCl4(en)]2- while the excess of chloride did not affect the square-pyramidal structure of [ZnCl2(terpy)]. The substitutions of studied complexes and relevant nucleophiles proceeded in two consecutive reaction steps that depended on the nucleophile concentration. Octahedral complex anion [ZnCl4(en)]2- forms rapidly and all substitution processes of this complex species should be considered. We assume that the first reaction step is accompanied by the dissociation of chloride ligands. Nucleophile 1,2,4- triazoles have shown the highest affinity toward [ZnCl2(en)], and rates of both steps were almost of the same value, indicating parallel reactions.
Conclusion: The different order of reactivity of relevant N-donor ligands toward [ZnCl2(en)] and [ZnCl2(terpy)] complexes for the first reaction step occurred because of the influence of different geometrical structures of complexes, while low reaction rates for the second reactions of [ZnCl2(en)] complex with imidazole and pyrazine were a consequence of interconversion between octahedral and tetrahedral structure during substitution processes.