<strong>Interaction of Zinc(II) Complexes with Relevant Nitrogen Nucleophiles under Physiological Conditions</strong>

Abstract

In recent years, the field of medicinal inorganic chemistry has received considerable attention for the design of anticancer agents. Zinc(II) ion plays an important role in bioinorganic processes because of the potential formation of coordination compounds in which zinc(II) ion can readily accommodate four-, five-, or six molecules. The advantage of zinc-based anticancer drugs could be their selectivity toward specific cellular targets thanks to specific coordination ability and kinetic properties  (Bertini I., et al., Biological Inorganic Chemistry. Structure and Reactivity, University Science Books: Sausalito, CA, 2007; Roat-Malone R.M. (Ed.), Bioinorganic Chemistry: A Short Course, John Wiley & Sons, Inc., Hoboken, NJ, 2002).  The mole-ratio method was used for determining metal-ligand stoichiometry between [ZnCl2(en)] (where en=  1,2-diaminoethane or ethylenediamine) and imidazole at pH 7.2 in the presence of different chloride concentrations. The results indicated step-wise formation of 1:1 and 1:2 complexes in the presence of 0.010 M NaCl and 1:1 complexes in the presence of 0.001 M NaCl. Those results are correlated with additional coordination of chlorides in the first coordination sphere and with changes in coordination geometry. In the presence of 0.001 M NaCl, five-coordinate complex anion [ZnCl3(en)]- is formed initially, and then substitution reaction with imidazole occurred. In the presence of 0.010 M NaCl the octahedral complex anion [ZnCl4(en)]2- formed. The kinetics of ligand substitution reactions between complex and relevant nitrogen nucleophiles such as imidazole, 1,2,3-triazole and L-histidine were investigated at pH 7.2 as a function of nucleophile concentration in the presence of 0.001 M and 0.010 M NaCl. The reactions were followed under pseudo-first-order conditions by UV-vis spectrophotometry. The substitution reactions included two steps of consecutive displacement of chlorido ligands and changes in coordination geometry of [ZnCl2(en)] complex. Results are discussed in terms of mechanisms of interactions between potential antitumor zinc-based drugs and biomolecules.