Aryl bismuth phosphinates [BiAr(O(O)PRR')]: structure-activity relationships for antibacterial activity and cytotoxicity.

To study and evaluate the structure-activity relationships in di-aryl bismuth phosphinates on antibacterial activity and cytotoxicity a series of complexes containing -methoxyphenyl, -methoxyphenyl, -tolyl and -tolyl aryl groups; [Bi(-MeOPh)(O(O)P(H)Ph)]1, [Bi(-MeOPh)(O(O)PPh)]2, [Bi(-MeOPh)(O(O)P(-MeOPh))]3, [Bi(-MeOPh)(O(O)P(H)Ph)]4, [Bi(-MeOPh)(O(O)PPh)]5, [Bi(-MeOPh)(O(O)P(-MeOPh))]6, [Bi(-tol)(O(O)P(H)Ph)]7, [Bi(-tol)(O(O)PPh)]8, [Bi(-tol)(O(O)P(-MeOPh))]9, [Bi(-tol)(O(O)P(H)Ph)]10, [Bi(-tol)(O(O)PPh)]11 and [Bi(-tol)(O(O)P(-MeOPh))]12, were synthesised and characterised. Complexes 4, 7, 8, 10 and 11 were structurally authenticated by X-ray crystallography. Evaluation of their antibacterial activity towards methicillin-resistant (MRSA), vancomycin-resistant (VRE), () and () showed that the bismuth bound aryl group has a profound influence on activity, with the -MeOPh complexes 1-3 showing very little activity while the -MeOPh complexes have the greatest activity towards MRSA and VRE in the range of 0.63 to 1.25 μM. Viability studies with Cos-7 cells showed that the di-aryl bismuth complexes 1-12 are less cytotoxic than their di-phenyl bismuth analogues, with a general trend of toxicity observed as -tolyl > -tolyl > -methoxyphenyl > -methoxyphenyl. The large difference in Cos-7 viability for complexes 1 (IC > 80 μM) and 4 (IC 14.0 μM) was further investigated through bismuth uptake studies, where there was no obvious difference in Cos-7 bismuth uptake at 5 μM. This suggests that the bismuth-bound aryl group has a significant impact on biological activity, which is then further mediated by other ligands.