Photophysical properties and biological evaluation of a Zinc(II)-5-methyl-1H-pyrazole Schiff base complex

A new ZnL₂ complex containing two molecules of a tridentate Schiff base derived from 5-methyl-1H-pyrazole (HL) is synthesized and characterized. The photophysical properties of HL and ZnL₂ are disclosed and supported by CAMB3LYP DFT/TDDFT calculations. It is shown that there is keto-tautomer stabilization upon excitation with an energetically accessible triplet state in HL, not present in ZnL₂, this explaining the differences found in the emissions of the compounds. The intrinsic fluorescence of ZnL₂ is used as probe for a detailed study of its binding to human serum albumin. The protein-complex association is thermodynamically favourable and it is shown by fluorescence quenching and time-resolved analysis that the fluorescence quenching involves a mixed mechanism with prevalence of static quenching, which corroborates adduct formation at site I, close to the Trp214 residue. The ability of ZnL₂ to bind DNA was also evaluated, as well as its cytotoxic activity against MCF7 (breast), PC3 (prostate) cancer cells and hamster V79 fibroblasts. ZnL₂ is a moderate DNA intercalator (K_app = 3.9 × 10⁴ M^-1) and depicts a quite low IC₅₀ value at 48 h against MCF7 cells (IC₅₀ = 530 nM), but much higher for PC3 and V79 cells. The relevance of a more careful speciation evaluation of ZnL₂ and other potential metal-based drugs in incubation media used in in vitro tests is highlighted.