Heterometallic bridged Pt(II)-Zn(II) complexes: Influence of the substituent in 4-position in inert terpy ligand on antigenotoxicity, potential antitumor activity and mechanism of interactions of the complexes with biomolecules

The synthesis and characterization of novel hetrometallic complexes [{cis-PtCl(NH3)2(mu-4,4 '-bipyridyl)ZnCl(terpy-Cl)}](ClO4)2 (C1a), [{trans-PtCl(NH3)2(mu-4,4 '-bipyridyl)ZnCl(terpy)}](ClO4)2 (C2a), [{cis-PtCl(NH3)2(mu-pyrazine)ZnCl(terpy-Cl)}](ClO4)2 (C3a) and [{trans-PtCl(NH3)2(mu-pyrazine)ZnCl(terpy-Cl)}](ClO4)2 (C4a) (where terpy-Cl = 4 '-chloro-2,2 ':6 ',2 ''-terpyridine) was done. Acid-base titrations were performed by UV-Vis spectrophotometric method to evaluate the pKa values of corresponding aqua complexes. Interactions between complexes and important biomolecules, guanosine-5 '-monophosphate (5 '-GMP) and glutathione (GSH) were examined by 1H NMR spectroscopy. The chloride substituent at the 4 ' position on the middle pyridine ring of terpyridine ligand significantly affects the coordination of biomolecules, as well as overall stability of complexes. The complexes were evaluated in vitro for the antioxidant prevention of DNA damages. All tested novel complexes demonstrated a significant reduction in DNA damage against oxidative modifications of DNA caused by the hydroxyl and peroxyl radicals. Also, cytotoxicity evaluation showed that significant cytotoxicity occurs only after long-term effect of C1a, C2a and C3a, complexes in HCT-116 cells. Molecular docking studies predict results in agreement with experimental research. The four novel complexes [{cis-PtCl(NH3)2(mu-4,4 '-bipy)ZnCl(terpy-Cl)}](ClO4)2, [{trans-PtCl(NH3)2(mu-4,4 '-bipyridyl)ZnCl(terpy)}](ClO4)2, [{cis-PtCl(NH3)2(mu-pyrazine)ZnCl(terpy-Cl)}](ClO4)2 and [{trans-PtCl(NH3)2(mu-pyrazine)ZnCl(terpy-Cl)}](ClO4)2 were synthesized and characterized. The chloride in 4 ' position of 2,2 ':6 ',2 ''-terpyridine has great influence on the stability of the complexes and their antitumor activity. image