Synthesis, characterisation and biological evaluation of novel bisimidazolium mononuclear and dinuclear silver(I)-N-heterocyclic carbene complexes with long N-alkyl chains

Abstract

Current drug research has been focusing on silver N-heterocyclic carbene (NHC) complex. Its metal-ligand bonds are stabilised by the strong-electron donor nature of NHC, ultimately increasing its antimicrobial properties. A series of imidazolium salts and their corresponding Ag(I)-NHC complexes with different NHC side chains in terms of alkyl chain length and mono/biscarbene functionalities have been successfully synthesised, characterised, and evaluated for their potential antimicrobial activities. It was shown that the imidazolium salts and Ag(I)-NHC complexes with long aliphatic alkyl N-1/N-3 side chains and bisimidazolium ligands possess promising bioactivities in general, with minimum inhibitory concentration (MIC) against microbes ranging from 0.12 to 7.81 µg/mL against selected six Gram-positive bacterial strains (Staphylococcus aureus and Enterococcus faecalis), two Gram-negative bacteria (Escherichia coli and Shigella flexneri) and two fungal strains (Candida albicans) for 2–7d & Ag-2–7d. It was found that the compounds with biscarbene structures (6d & Ag-6d) possess less toxic effects against immortalised human keratinocyte (HaCaT) cells. However, it must be noted that the toxic effect against HaCaT is higher among Ag(I)-NHC complexes (Ag-4d & Ag-6d) than their corresponding imidazolium salts (4d & 6d) in general. Hence, the variation of side chains, number of imidazolium centres and their respective cytotoxic effect provide insights into the future drug modification towards enhanced antimicrobial activities with minimal side effects.