Interactions of zinc(II) complexes with 5′-GMP and their cytotoxic activity

Abstract

The mechanism of substitution from tetrahedral [ZnCl₂(en)] and square-pyramidal [ZnCl₂(terpy)] complexes (where en = 1,2-diaminoethane or ethylenediamine and terpy = 2,2′:6′,2′′-terpyridine) by guanosine-5′-monophosphate (5′-GMP) have been investigated by ¹H NMR spectroscopy. The substitution reaction of [ZnCl₂(terpy)] complex is faster than the reaction of [ZnCl₂(en)], which was finished after 48 h. Information about the structures of the final products in solution were obtained from the DFT calculations (B3LYP/6-31G(d)) and experimental ¹H NMR data acquired during the course of the reaction. The cytotoxic activity of zinc(II) complexes was tested on human breast cancer cell line MDA-MB-231, human colon cancer cell line HCT-116 and normal human lung fibroblast cell line MRC-5. Both complexes reduced cell viabilities, while [ZnCl₂(terpy)] was significantly cytotoxic on MDA-MB-231 after 72 h, and HCT-116 after 24 h without dose dependence. The differences in reactivity toward 5′-GMP and cytotoxic activity of Zn(II) complexes may be attributed to the very stable square-pyramidal geometry of [ZnCl₂(terpy)] in solution, while weak ligand effect of the en compared to the terpy affected slow interaction of tetrahedral [ZnCl₂(en)] complex with the target bio-molecule.

Graphical Abstract

Keywords:

• Zinc(II) complexes
• guanosine-5′-monophosphate
• 1H NMR
• DFT calculations
• structure-reactivity correlation
• anticancer cytotoxic activity

Acknowledgments

T. Soldatović and E. Selimović gratefully acknowledge financial support from State University of Novi Pazar, Novi Pazar, Republic of Serbia. R. Puchta would like to thank the Regionales Rechenzentrum Erlangen (RRZE) for a generous allotment of computer time and Prof. Tim Clark for hosting this work at the CCC. B.M. Alzoubi thanks Al-Balqa Applied University for its support. The authors are grateful for the support to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project Nos. III41010, OI172016 and OI172036).

Disclosure statement

No potential conflict of interest was reported by the authors.