Novel Nonsymmetrically p -Benzyl-Substituted (Benz)imidazole N -Heterocyclic Carbene-Silver(I) Acetate Complexes: Synthesis and Biological Evaluation

Abstract

Nonsymmetrically substituted N -heterocyclic carbene (NHC) precursors 1a – d and 3a – d were synthesised by first reacting 1H-(benz)imidazole with p -cyanobenzyl bromide to give 4-(1H-imidazole-1-ylmethyl)benzonitrile ( 1 ) and 4-(1H-benzimidazole-1-ylmethyl)benzonitrile ( 3 ) and afterwards introducing benzyl bromide, 1-(bromomethyl)-4-methylbenzene, 1-(bromomethyl)-4-methoxybenzene, and methyl 4-(bromomethyl)benzoate. The NHC-silver(I) acetate complexes (1-benzyl-3-(4-cyanobenzyl)-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate ( 2a ), (1-(4-cyanobenzyl)-3-(4-methylbenzyl)-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate ( 2b ), (1-(4-cyanobenzyl)-3-[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-imidazole-2-ylidene) silver(I) acetate ( 2c ), (1-benzyl-3-(4-cyanobenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate ( 4a ), (1-(4-cyanobenzyl)-3-(4-methylbenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate ( 4b ), (1-(4-cyanobenzyl)-3-(4-methoxybenzyl)-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate ( 4c ), and (1-(4-cyanobenzyl)-3-[4-(methoxycarbonyl)benzyl]-2,3-dihydro-1H-benzimidazole-2-ylidene) silver(I) acetate ( 4d ) were yielded by reacting these NHC precursors with silver(I) acetate. The silver(I) acetate complex 4b was characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial studies against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli , using the Kirby-Bauer disc diffusion method, were carried out on the seven NHC-silver(I) acetate complexes 2a – c and 4a – d . Also the IC 50 values of these seven complexes were determined by an MTT-based assay against the human renal cancer cell line Caki-1. The complexes 2a – c and 4a – c revealed the following IC 50 values, respectively, 25 (±1), 15 (±2), 5.4 (±0.8), 16 (±2), 7.1 (±1), 20 (±4), and 14 (±1) μ M.