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

A new ZnL 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 ZnL 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 ZnL, this explaining the differences found in the emissions of the compounds. The intrinsic fluorescence of ZnL 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 ZnL to bind DNA was also evaluated, as well as its cytotoxic activity against MCF7 (breast), PC3 (prostate) cancer cells and hamster V79 fibroblasts. ZnL is a moderate DNA intercalator (K = 3.9 × 10 M) and depicts a quite low IC value at 48 h against MCF7 cells (IC = 530 nM), but much higher for PC3 and V79 cells. The relevance of a more careful speciation evaluation of ZnL and other potential metal-based drugs in incubation media used in in vitro tests is highlighted.