Silver(I) and gold(I) complexes with sulfasalazine: Spectroscopic characterization, theoretical studies and antiproliferative activities over Gram-positive and Gram-negative bacterial strains

Abstract

The emergence of bacterial strains resistant to antibiotics, such as the sulfonamides (sulfa drugs), is currently a case of concern. The synthesis of metal complexes using well-known antibacterial agents and bioactive metals has proven to be an excellent strategy in the development of new and more active metallodrugs. Herein, we report the synthesis, structural characterization and antibacterial analysis of new gold(I) and silver(I) complexes with the sulfa drug sulfasalazine (ssz). Elemental, thermal and high-resolution mass spectrometric measurements indicated a 1:1:1 Au/ssz/Ph3P molar composition for the gold(I) complex (Ph3P - triphenylphosphine), while for the silver(I) complex the molar composition was 1:1 Ag/ssz. Solution state NMR and infrared spectroscopic data suggest that ssz coordinates to silver(I) and gold(I) by the oxygen atoms of the deprotonated carboxylic group. The coordination mode of the carboxylate was supported by density functional theory (DFT) calculations, which reinforces a monodentate coordination for the gold(I) complex and a bridged bidentate mode for the silver(I) one, with the molecular formulas [(Ph3P)Au(ssz)] and [Ag(ssz)]2, respectively. Antibacterial activity assays indicated the sensitivity of Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains to [Ag(ssz)]2 and [(Ph3P)Au(ssz)] complexes, while the free ligand was not able to inhibit the growth of any tested bacteria. The non-interaction of the complexes with deoxyribonucleic acid (DNA) was also demonstrated, which suggests that this biomolecule is not a preferential target for the compounds.