Theoretical and experimental studies of ligand exchange reaction models and their correlation with antileishmanial activity of gold-NHC complexes

Leishmaniases are a group of neglected tropical diseases in need of new therapeutic options. Our group investigates the use of gold complexes as potential metallodrugs for these diseases, which have already shown great promise. Part of this activity stems from activation, deactivation, and action phenomena through ligand exchange reactions, particularly with thiols present in the active sites of Trypanothione Reductase (a vital enzyme for the redox homeostasis of the Leishmania parasite). Ligand exchange reaction models with small molecules are investigated in this work using experimental and computational techniques. Computational studies using Density Functional Theory indicate that the direct reaction of the complexes with cysteine is more favorable than through the formation of an aquation intermediate, in addition to demonstrating a direct correlation between the reaction Δ_rG° with cysteine and the HOMO-LUMO GAP of the complexes (complexes with smaller HOMO-LUMO GAPs are more reactive toward cysteine).