Effect of lipophilicity of wingtip groups on the anticancer potential of mono N‐heterocyclic carbene silver(I) complexes: Synthesis, crystal structures and in vitro anticancer study

Abstract

A series of symmetrically n‐alkyl‐substituted mono benzimidazolium salts with steady increase in n‐alkyl chain length have been prepared by stepwise N‐alkylation resulting in salts (1–8). The mono N‐heterocyclic carbene (NHC)–Ag(I) complexes (9–16) derived from the respective salts were readily accessible by in situ deprotonation using Ag2O. All the salts and the complexes were characterized using Fourier transform infrared, 1H NMR, 13C NMR and elemental analyses. Furthermore, the structures of salts 3 and 7 and complex 16 were elucidated using X‐ray crystallography, which established that this mono NHC–Ag(I) complex has a linear bis‐carbene arrangement (C2–Ag). The proligands and the respective Ag(I) complexes were studied for their in vitro anticancer potential against human colon cancer cell line (HCT‐116) using 5‐fluorouracil as a standard. From the IC50 values of all the tested compounds, it can be postulated that there is an influential relationship between the increase in chain length of the wingtip n‐alkyl groups and the anticancer potential. The proligands 4–8 and their respective complexes 12–16 with long n‐alkyl chain lengths (n = 6–10) showed better IC50 values (0.3–3.9 μM) than the standard drug with the complexes displaying markedly better antiproliferation activity against HCT‐116 cell line than the respective proligands and the standard drug (IC50 = 10.2 μM).