Effects of supramolecular interactions in nitrile functionalized silver(I)-N-heterocyclic carbene complexes and investigation into their enhancement of antitumor metallodrugs

Abstract

A series of aliphatic nitrile functionalized benzimidazolium salts, 1-6, and their respective mononuclear Ag(I)- NHC complexes, 7-12, are reported. Salts 1-6 were synthesized by the suitable method of N-alkylation, where 1H- benzimidazole was initially reacted with an appropriate alkyl bromide, followed by reaction with either 5- bromovaleronitrile or 6-bromohexanenitrile. The respective mononuclear Ag(I)-NHC complexes 7-12 were prepared by the reaction of the benzimidazolium salts with Ag2O. All the synthesized compounds were characterized by 1H-NMR, 13C-NMR, and FTIR spectroscopy. The molecular structure of complexes 7 and 11 was elucidated through single-crystal X-ray diffraction analyses. The benzimidazolium salts and their respective Ag(I)-NHC complexes were screened for their potential cytotoxicity on breast cancer cell line (MCF-7), using MTT assay. The presence of supramolecular interactions between Ag(I) ions and the nitrile groups are observed to support the cytotoxicity properties of the complexes by slowing down the releasing rate of the metal ions. All the Ag(I)-NHC complexes show slightly better or lesser activity with IC50 values ranging from 7.0±1.06 – 12.9±1.55 µM in comparison with the standard drug, Tamoxifen (IC50 = 11.2±1.84 µM). All the respective benzimidazolium salts, however, were found to be inactive.