Synthesis, Cytotoxicity and Antibacterial Studies of <i>p</i>‐Methoxybenzyl‐Substituted and Benzyl‐Substituted N‐Heterocyclic Carbene–Silver Complexes

Abstract

Abstract p ‐Methoxybenzyl‐substituted and benzyl‐substituted N‐heterocyclic carbene (NHC) [( 3a – c ) and ( 6a – c )] precursors were synthesised from the reaction of 1 H ‐imidazole ( 1a ), 4,5‐dichloro‐1 H ‐imidazole ( 1b ), and 1 H ‐benzimidazole ( 1c ) with p ‐methoxybenzyl bromide ( 2 ) and benzyl bromide ( 5 ). These NHC precursors were then treated with silver(I) acetate to yield the NHC–silver complexes [1,3‐bis(4‐methoxybenzyl)imidazol‐2‐ylidene]silver(I) acetate ( 4a ), [4,5‐dichloro‐1,3‐bis(4‐methoxybenzyl)imidazol‐2‐ylidene]silver(I) acetate ( 4b ), [1,3‐bis(4‐methoxybenzyl)benzimidazol‐2‐ylidene]silver(I) acetate ( 4c ), (1,3‐dibenzylimidazol‐2‐ylidene)silver(I) acetate ( 7a ), (1,3‐dibenzyl‐4,5‐dichloroimidazol‐2‐ylidene)silver(I) acetate ( 7b ), and (1,3‐dibenzylbenzimidazol‐2‐ylidene)silver(I) acetate ( 7c ), respectively. The NHC precursor 3c , four NHC–silver complexes 4c and 7a – c were characterised by single‐crystal X‐ray diffraction method. The preliminary antibacterial activity of all the compounds was studied against Gram‐negative bacteria Escherichia coli , and Gram‐positive bacteria Staphylococcus aureus using the Kirby–Bauer disk‐diffusion method. Almost all the NHC–silver complexes have shown high antibacterial activity compared to the NHC precursors. In addition, the NHC–silver complexes had their cytotoxicity investigated through MTT‐based preliminary in vitro testing on the Caki‐1 cell lines in order to determine their IC 50 values. NHC–silver complexes 4a – c and 7a – c were found to have IC 50 values of 7.3 (+/–6), 12.7(+/–3), 25.2 (+/–5), 2.5 (+/–3), 10.8 (+/–4) and 12.5 (+/–4) μ M respectively on the Caki‐1 cell line.