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.

Graphical Abstract

Keywords:

• Heterometallic complexes
• Zinc(II) and copper(II)
• biomolecules
• antimicrobial activity
• cytotoxic activity

Acknowledgement

T. Soldatović and E. Selimović gratefully acknowledge financial support from State University of Novi Pazar, Republic of Serbia. The authors gratefully acknowledge financial support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Agreement Nos. 451-03-68/2022-14/ 200252, 451-03-68/2022-14/200378 and 451-03-68/2022-14/200122).

Disclosure statement

There are no conflicts of interest to declare.