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

✍ Scribed by Siddappa Patil; Karolin Dietrich; Anthony Deally; Brendan Gleeson; Helge Müller-Bunz; Francesca Paradisi; Matthias Tacke

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: German
• Weight: 464 KB
• Volume: 93
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.201000310

✦ Synopsis

Abstract

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 μM.