Synthesis, Cytotoxicity and Antibacterial Studies of Novel Symmetrically and Nonsymmetrically 4‐(Methoxycarbonyl)benzyl‐Substituted N ‐Heterocyclic Carbene–Silver Acetate Complexes

From the reaction of 1 H ‐imidazole ( 1a ), 4,5‐dichloro‐1 H ‐imidazole ( 1b ), 1 H ‐benzimidazole ( 1c ), 1‐methyl‐1 H ‐imidazole ( 1d ), and 1‐methyl‐1 H ‐benzimidazole ( 1f ) with methyl 4‐(bromomethyl)benzoate ( 2 ), symmetrically and nonsymmetrically 4‐(methoxycarbonyl)benzyl‐substituted N ‐heterocyclic carbene (NHC) precursors, 3a – 3f , were synthesized. These NHC precursors were then reacted with silver(I) acetate (AgOAc) to yield the NHC–silver acetate complexes (acetato‐ κO ){1,3‐bis[4‐(methoxycarbonyl)benzyl]imidazol‐2‐ylidene}silver ( 4a ), (acetato‐ κO ){4,5‐dichloro‐1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1 H ‐imidazol‐2‐yl}silver ( 4b ), (acetato‐ κO ){1,3‐bis[4‐(methoxycarbonyl)benzyl]‐2,3‐dihydro‐1 H ‐benzimidazol‐2‐yl}silver ( 4c ), (acetato‐ κO ){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1 H ‐imidazol‐2‐yl}silver ( 4d ), (acetato‐κ O ){4,5‐dichloro‐1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1 H ‐imidazol‐2‐yl}silver ( 4e ), and (acetato‐ κO ){1‐[4‐(methoxycarbonyl)benzyl]‐3‐methyl‐2,3‐dihydro‐1 H ‐benzimidazol‐2‐yl}silver ( 4f ), respectively. The three NHC–AgOAc complexes 4a, 4c , and 4d were characterized by single‐crystal X‐ray diffraction. All compounds studied in this work were preliminarily screened for their antimicrobial activities in vitro against Gram ‐positive bacteria Staphylococcus aureus , and Gram ‐negative bacteria Escherichia coli using the qualitative disk‐diffusion method . All NHC–AgOAc complexes exhibited weak‐to‐medium antibacterial activity with areas of clearance ranging from 4 to 7 mm at the highest amount used, while the NHC precursors showed significantly lower activity. In addition, NHC–AgOAc complexes 4a and 4b , and 4d – 4f exhibited in preliminary cytotoxicity tests on the human renal‐cancer cell line Caki‐1 medium‐to‐high cytotoxicities with IC 50 values ranging from 3.3±0.4 to 68.3±1 μ M .