Pyrazine Functionalized Ag(I) and Au(I)-NHC Complexes are Potential Antibacterial Agents

Antimicrobial resistance is an ever-increasing problem throughout the world and has already reached severe proportions. Bacteria can develop ways to render traditional antibiotics ineffective, raising a crucial need to find new antimicrobials with novel mode of action. We demonstrate here a novel class of pyrazine functionalized Ag(I) and Au(I)-NHC complexes as antibacterial agents against human pathogens that are resistant to several antibiotics. Complete synthetic and structural studies of Au(I) and Ag(I) complexes of 2-(1- methylimidazolium) pyrimidinechloride (L-1), 2,6-bis(1-methylimidazol)pyrazinechloride (L-2) and 2,6-bis(1-methyl imidazol) pyrazinehexa-fluorophosphate (L-3) are reported herein. Chloro[2,6-bis(1-methyl imidazol)pyrazine]gold(I), 2b and chloro [2,6-bis(1- methyl imidazol)pyrazine]silver(I), 2a complexes are found to have more potent antimicrobial activity than other synthesized compounds and several conventionally used antibiotics. Complexes 2b and 2a also inhibit the biofilm formation by Gram-positive bacteria, Streptococcus mutans and Gram-negative bacteria, Escherichia coli, causing drastic damage to the bacterial cell wall and increasing membrane permeability. Complexes 2b and 2a strongly binds to both Lys and Dap-Type peptidoglycan layers, which may be the reason for damage to the bacterial cell wall. Theoretical studies of all the complexes reveal that 2b and 2a are more reactive than other complexes, and this may be the cause of differences in antibacterial activity. These findings will pave the way towards developing a new class of antibiotics against different groups of conventional antibiotic-resistant bacteria.