Homoleptic and Heteroleptic Bismuth(III) Thiazole–Thiolates and the Influence of Ring Substitution on Their Antibacterial and Antileishmanial Activity

Abstract

AbstractTwo new homo‐ and heteroleptic bismuth thiazole‐thiolato complexes derived from 4‐phenylthiazole‐2‐thiol MBT(H) have been synthesised and structurally characterised, [BiPh(MBT)2]2 and [Bi(MBT)3]2. Syntheses were achieved using BiPh3 or Bi(OtBu)3 in protolysis reactions with MBT(H), or by salt metathesis with BiCl3 or BiPhCl2 and the sodium thiolate, [NaMBT]. The complexes were obtained under both standard solvent‐free and solvent‐mediated conditions, and by microwave irradiation. The solid‐state structures of [BiPh(MBT)2]2 and [Bi(MBT)3]2, were determined using single‐crystal X‐ray diffraction, showing them to be dimeric. The bactericidal properties of the complexes against Mycobacterium smegmatis, Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, vancomycin‐resistant Enterococcus (VRE) and Escherichia coli revealed [BiPh(MBT)2]2 to be the most effective against all the bacteria with MIC values of 0.6 μg/mL (0.25 μM) against S. aureus and 0.9 μg/mL (0.27 μM) against E. faecalis. [Bi(MBT)3]2 was less active overall. However, comparisons with the analogous complex [Bi(4‐BrMTD)3], revealed a significant hundred‐fold enhanced activity against S. aureus, MRSA, VRE, and E. faecalis. Both complexes showed little or no toxicity towards mammalian COS‐7 cells at 20 μg/mL. [BiPh(MBT)2]2 also was found to display good antileishmanial activity with an IC50 value of 0.11 μg/mL (0.17 μM), at which concentration the complex was non‐toxic to human fibroblast cells.