Synthesis and antimicrobial activity of thiophene-functionalized Ag(I) and Au(I) N-heterocyclic carbene complexes against ampicillin-resistant Staphylococcus aureus

New antibacterial agents with novel actions are vital to treat drug-resistant bacterial infections. Silver and gold-based organometallic N-heterocyclic carbene (NHC) complexes have emerged as promising candidates with notable antibacterial potential. Here, four new Ag(I)- and Au(I)-NHCcomplexes, 1a, 1b, and 2a, 2b, have been synthesized from the proligand 2-(thiophen-2-ylmethyl)-2H-imidazo[1,5-α]pyridine-4-ium hexafluorophosphate and 1-methyl 2-(thiophen-2-ylmethyl)-2H-imidazo[1,5-α]pyridine-4-ium hexafluorophosphate, respectively, and characterized using several spectroscopic techniques. All the NHC complexes 1a, 1b, 2a, and 2b were revealed to have antimicrobial activity against ampicillin resistant Staphylococcus aureus, ranging from 32 to 256 µg/mL. Complex 1b and 2b showed a MIC value of 64 and 32 µg/mL, respectively which is further reduced eightfolds when used in combination with ampicillin. The most potential NHC complex 2b is also efficiently able to eradicate S. aureus biofilms in the presence of ampicillin. Electron microscopy and molecular docking studies demonstrated significant cell membrane disruption accompanied by a marked depletion of the intracellular ATP pooland β-lactamase inhibition as major mechanisms of action against ampicillin-resistant S. aureus. Thus, thiophene-functionalized Ag(I) and Au(I)-NHC complexes could be developed as potential antibacterial agents to control drug-resistant bacteria and infections.