Novel heterometallic Zn(II)-L-Cu(II) complexes: studies of the nucleophilic substitution reactions, antimicrobial, redox and cytotoxic activity

Abstract

New heterometallic complexes [{ZnCl(terpy)(μ-pyrazine)CuCl(terpy)}] (ClO4)2 (Zn-L1-Cu) and [{ZnCl(terpy)(μ-4,4′-bipyridyl)CuCl(terpy)}] (ClO4)2 (Zn-L2-Cu) (where terpy = 2,2′:6′,2′′-terpyridine, L1 = pyrazine, L2 = 4,4′-bipyridyl) were synthesized. The substitution reactions with biologically important nucleophiles were investigated at pH 7.4 by UV-Vis spectrophotometric method. The obtained results have shown different orders of reactivity of guanosine-5′-monophosphate (5′-GMP), inosine-5′-monophosphate (5′-IMP) and glutathione (GSH) toward heterometallic Zn(II)-L-Cu(II) complexes. Spectrophotometric titration of diaqua Zn-L-Cu complexes has shown that aqua ligands coordinated to both metal centers can exhibit different pK a values depending on the distance between them. Both synthesized complexes showed moderate antimicrobial activity against most of the tested bacterial and fungal strains. The cytotoxic activity of heteronuclear Zn-L1-Cu and Zn-L2-Cu complexes was determined on human colorectal cancer (HCT-116) and human healthy lung pleura (MRC-5) cell lines. Both complexes exerted significant cytotoxic effects, especially after 72 h (IC50 < 0.01 µM) and significantly reduced cell viability. Complexes induced a significant increase in reactive radical species which consequently induced cell death and thus lower IC50 values. As the response of the cells to an increased radical level induced by treatment, glutathione level also increased in a time and dose-dependent manner.