The Importance of Heterolepticity in Improving the Antibacterial Activity of Bismuth(III) Thiolates

Five mixed thiolatobismuth(III) complexes [BiPh-(5-MMTD)(2){4-MMT(H)}] (1), [Bi(1-MMTZ)(2){(PYM)(PYM(H))(2)}] (2), [Bi(MBT)(2)(5-MMTD)] (3), [Bi(4-BrMTD)(3){2-MMI(H)}] (4) and [Bi(1-MMTZ)(2){1-MMTZ(H)}(2-MMI){2-MMI(H)(2)}] (5) were synthesised from imidazole-, thiazole-, thiadiazole-, triazole-, tetrazole-and pyrimidine-based heterocyclic thiones. Four of these complexes 1-4 were synthesized from BiPh3, while complex 5 was obtained from Bi[4-(MeO)Ph](3). Complexes 1-5 were structurally characterised by XRD. Evaluation of the antibacterial properties against Mycobacterium smegmatis, Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Vancomycin-resistant Entero-coccus (VRE), Enterococcus faecalis and Escherichia coli showed that mixed thiolato complexes containing the anionic thiazolebased ligands MBT and 4-BrMTD are most effective. The mixed thiolato complexes [Bi(MBT)(2)(5-MMTD)] (3) having thiazole-and thiadiazole-and [Bi(4-BrMBT)(3){2-MMI(H)}] (4) containing thiazole- and imidazole-based ligands proved to be more efficient, with low minimum inhibitory concentrations of 1.73 and 3.45 mu M for 3 against VRE and E. faecalis, respectively, and 2.20 mu M for 4 against M. smegmatis and E. faecalis. All complexes showed little or no toxicity towards mammalian COS-7 cell lines at 20 mu g mL(-1).