Aryl bismuth phosphinates [BiAr2(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 ortho-methoxyphenyl, meta-methoxyphenyl, meta-tolyl and para-tolyl aryl groups; [Bi(o-MeOPh)(2)(O(O)P(H)Ph)](n), [Bi(o-MeOPh)(2)(O(O)PPh2)](n) 2, [Bi(o-MeOPh)(2)(O(O)P(p-MeOPh)(2))](n) 3, (Bi(m-MeOPh)(2)(O(O)P(H)Ph)](n) 4, [Bi(m-MeOPh)(2)(O(O)PPh2)](n) 5, [Bi(m-MeOPh)(2)(O(O)P(p-MeOPh)(2))](n) 6, (Bi(m-tol)(2)(O(O)P(H)Ph)](n) 7, (Bi(m-tol)(2)(O(O)PPh2)](n) 8, [Bi(mtol)(2)(O(O)P(p-MeOPh)(2))](n) 9, [Bi(p-tol)(2)(O(O)P(H)Ph)](n) 10, (Bi(p-tol)(2)(O(O)PPh2)](n) 11 and [Bi(p-tol)(2)(O(O)P (p-MeOPh)(2))](n) 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 Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) showed that the bismuth bound aryl group has a profound influence on activity, with the o-MeOPh complexes 1-3 showing very little activity while the m-MeOPh complexes have the greatest activity towards MRSA and VRE in the range of 0.63 to 125 mu M. Viability studies with Cos-7 cells showed that the di-aryl bismuth complexes 1 12 are less cytotoxic than their diphenyl bismuth analogues, with a general trend of toxicity observed as p-tolyl > m-tolyl > m-methoxyphenyl > o-methoxyphenyl. The large difference in Cos-7 viability for complexes 1 (IC50 > 80 mu M) and 4 (IC50 14.0 mu M) was further investigated through bismuth uptake studies, where there was no obvious difference in Cos-7 bismuth uptake at 5 mu M. This suggests that the bismuth-bound aryl group has a significant impact on biological activity, which is then further mediated by other ligands.

Automated summary

The study focused on the structure activity relationships of di-aryl bismuth phosphinates and their antibacterial activity and cytotoxicity. The results showed that the bismuth-bound aryl groups significantly influenced the activity, with some complexes exhibiting strong antibacterial activity.