Insights into the mechanism of binding of the gold(III) dithiocarbamate derivatives to cysteine or DNA purine bases

Abstract

Complexes Au(DMDT)Br2 (DMDT = N,N-dimethyldithiocarbamate), Au(ESDT)Br2 (ESDT = ethylsarcosinedithiocarbamate) and Au(ESDT)Cl2 are likely to be considered as important candidates for antitumor agents. In the reactions, there is H-bond reciprocity between attacking group and H2O so that it will enhance the stability of the whole structure. On the basis of the optimized gas-phase geometry, the data of monofunctional reactions indicate that the S site of cysteine is superior to other active sites, and by analyzing the order of the activation barriers of two gold compounds with different halogen ligand in the bromoaqua (chloroaqua) substitution reaction, we discover that different halogen ligand has a slight effect on substitution reaction in the aqueous solution. Meanwhile, the cysteine as a drug target is better than purine bases. Afterward, we performed geometry optimizations in two different environments (gas phase and aqueous solution). Follow on to the bifunctional substitution reactions based on the optimized gas-phase geometry, except for the reaction when diaqua adduct [Au(ESDT)Cys(S, N)(H2O)]2+ acts as reactant, all the energy barriers of cysteine’s S as attack site are the lowest in the aqueous solution. Nevertheless, on the basis of the optimized aqueous solution geometry, our computations show that cysteine’s O site is superior to other targets in the bifunctional substitution reaction, when monofunctional adduct [Au(ESDT)Cys(S, N)(H2O)]2+ acts as reactant in the aqueous solution. Therefore, this conclusion by our calculations obtained is found to be in line with some laboratory experimental results. Besides, in the whole substitution reactions, the environmental influences should not be ignored.