Chirality influence on the cytotoxic properties of anionic chiral bis (N-heterocyclic carbene)silver complexes

Complexes Na3[Ag(NHCR)2], 2a -e and 2b' -c', where NHCR is a N-heterocyclic carbene of the 2,2'-(1H-2 lambda 3,3 lambda 4- imidazole-1,3-diyl)dicarboxylate type, were prepared by treatment of compounds HLR, 1a -e and 1b' -c' (2-(1-(carboxyalkyl)-1H-imidazol-3-ium-3-yl)carboxylate), with silver oxide in the presence of aqueous sodium hy-droxide. They were characterized by analytical, spectroscopic (infrared, IR, H-1 and C-13 nuclear magnetic reso-nance, NMR, and circular dichroism) and X-ray methods (2a). In the solid state, the anionic part of complex 2a, [Ag(NHCH)2]3-, shows a linear disposition of Ccarbene-Ag-Ccarbene atoms and an eclipsed conformation of the two NHC ligands. The proposed bis(NHC) nature of the silver complexes was maintained in solution according to NMR and density functional theory (DFT) calculations. The cytotoxic activity of compounds 2 was evaluated against four cancer cell lines and one non-cancerous cell line and several structure-activity correlations were found for these complexes. For instance, the activity decreased when the bulkiness of the R alkyl group in Na3[Ag (NHCR)2] increased. More interesting is the detected chirality-anticancer relationship, where complexes Na3[Ag {(S,S)-NHCR}2] (R = Me, 2b; iPr, 2c) showed better anticancer activity than those of their enantiomeric de-rivatives Na3[Ag{(R,R)-NHCR}2] (R = Me, 2b'; iPr, 2c').

Automated summary

A series of silver complexes were synthesized and characterized by various analytical methods, indicating the maintenance of N-heterocyclic carbene properties in solution. In the evaluation of anticancer activity, it was found that the activity of silver complexes was affected by the volume of R alkyl group, and the chirality also had an impact on anticancer activity.