Synthesis, crystal structures, in vitro anticancer, and in vivo acute oral toxicity studies of bis-imidazolium/benzimidazolium salts and respective dinuclear Ag(I)-N-heterocyclic carbene complexes

Abstract

The synthesis, spectral (FT-IR and NMR), and structural studies of 1,1′-methylene linked 3,3′-2-cyanobenzyl bis-imidazolium salt (L1) and respective dinuclear Ag(I)-NHC complex (C1) are reported. The structures of both compounds were established through single-crystal X-ray diffraction. C1 has a short Ag–Ag separation of 3.16 Å. Both L1 and C1 were tested for potential against leukemia (k562) cell line. For comparison, para-xylyl linked bis-benzimidazolium salts (L2–L4) and their dinuclear Ag(I)-NHC complexes (C2–C4) were synthesized and tested against the same cell line (K562). The IC50 values proved that L2–L4 and C2–C4 are many fold more active than L1 and C1. The mechanism of action and structure activity relationship are discussed. In vivo oral acute toxicity study (sighting study) was carried out which depicts that 2000 mg/kg dose of selected compounds is an appropriate and safe dose for conducting main study on animals.