Synthesis, Cytotoxicity and Antibacterial Studies of p-Methoxybenzyl-Substituted and Benzyl-Substituted N-Heterocyclic Carbene–Silver Complexes

摘要

p-Methoxybenzyl-substituted and benzyl-substituted Nheterocyclic carbene (NHC) [(3a–c) and (6a–c)] precursors were synthesised from the reaction of 1H-imidazole (1a), 4,5- dichloro-1H-imidazole (1b), and 1H-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 Grampositive 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 IC50 values. NHC–silver complexes 4a–c and 7a–c were found to have IC50 values of 7.3 (+/–6), 12.7 +/ –3), 25.2 (+/–5), 2.5 (+/–3), 10.8 (+/–4) and 12.5 (+/–4) μMrespectively on the Caki-1 cell line.