Experimental and theoretical studies of the substitution reactions of some bifunctional Au(III) complexes with biologically relevant thiols and thioethers

The kinetics of the substitution reactions between bifunctional Au(III) complexes, [AuCl2(bipy)](+), [AuCl2(dach)](+) and [AuCl2(en)](+) (bipy = 2,2 ''-bipyridine, dach = (1 R,2R)-1,2-diaminocyclohexane, en = ethylenediamine), with biologically relevant ligands such as glutathione (GSH), L-methionine (L-Met) and L-cysteine (L-Cys) is determined. All kinetic studies are performed in 25 mM Hepes buffer (pH = 7.2) in the presence of NaCl (25 mM) to prevent hydrolysis of the complexes. The reactions were followed under pseudo-first-order conditions using stopped-flow UV-Vis spectrophotometry at determined working wavelengths at three different temperatures (288.2, 298.1, and 309.8 K). DFT theoretical approach was applied to calculate thermodynamic and kinetic parameters that determined an operative mechanism of substitution reactions for all complexes and L-Cys as a selected model substituent. The obtained kinetic data showed that all complexes have similar reactivity; [AuCl2(bipy)](+) is the most reactive while [AuCl2(en)](+) is the least reactive. The second step of the substitution reaction is much faster than the first. The reactivity of the studied nucleophiles decreases in order L-Met > L-Cys > GSH. According to the values of the activation parameters determined experimentally and theoretically, all substitutions follow an associative model.