Gold(I) Bis(NHC) Complexes: Structural Variation on Wingtips and Their Leishmanicidal Activity

The development of new treatments for leishmaniasis is urgent due to adverse effects of current drugs. Gold(I) bis(N-heterocyclic carbene) (NHC) complexes are promising alternatives because structural modification of N-wingtips allows tuning of chemical and biological properties. In this study, Gold(I) biscarbene complexes were synthesized and characterized to evaluate activity against Leishmania amazonensis. Complexes 1 and 2 were prepared with aryl NHC ligands using adapted procedures, while novel complexes 3 and 4 were obtained via weak base methodology. All compounds were characterized by NMR, UV–Vis, mass spectrometry, FT-IR, and elemental analysis. Lipophilicity was determined by shake-flask method and human serum albumin binding constants were measured via Stern–Volmer approach. All complexes showed negative Log P values and strong activity against promastigote forms. IC₅₀ studies in macrophages, TRx inhibition, and DNA interactions are ongoing. DFT calculations suggest electronic effects do not explain kinetic differences in ligand substitution, indicating solubility as key factor.