Antimicrobial Activity of Anionic Bis(N-Heterocyclic Carbene) Silver Complexes

The antimicrobial properties of a series of anionic bis(carbene) silver complexes Na₃[Ag(NHC^R)₂] were investigated (<b>2a</b>-<b>2g</b> and <b>2c'</b>, where NHC^R is a 2,2'-(imidazol-2-ylidene)dicarboxylate-type <i>N</i>-heterocyclic carbene). The complexes were synthesized by the interaction of imidazolium dicarboxylate compounds with silver oxide in the presence of aqueous sodium hydroxide. Complexes <b>2f</b>,<b>g</b> were characterized analytically and spectroscopically, and the ligand precursor <b>1f</b> and complexes <b>2c</b> and <b>2g</b> were structurally identified by X-ray diffraction methods. The anions of <b>2c</b> and <b>2g</b>, [Ag(NHC^R)₂]^3-, showed a typical linear disposition of C_carbene-Ag-C_carbene atoms and an uncommonly eclipsed conformation of carbene ligands. The antimicrobial properties of complexes <b>2a</b>-<b>g</b>, which contains chiral (<b>2b</b>-<b>2e</b> and <b>2c'</b>) and non-chiral derivatives (<b>2a</b>,<b>f</b>,<b>g</b>), were evaluated against Gram-negative bacteria, <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>, and a Gram-positive bacterium, <i>Staphylococcus aureus</i>. From the observed values of the minimal inhibitory concentration and minimal bactericidal concentration, complexes <b>2a</b> and <b>2b</b> showed the best antimicrobial activity against all strains. An interesting chirality-antimicrobial relationship was found, and eutomer <b>2c'</b> showed better activity than its enantiomer <b>2c</b> against the three bacteria. Furthermore, these complexes were investigated experimentally and theoretically by ¹⁰⁹Ag nuclear magnetic resonance, and the electronic and steric characteristics of the dianionic carbene ligands were also examined.