Fluorinated <i>N</i>‑Heterocyclic\nCarbene Silver(I) Complexes with High Cancer Cell Selectivity

This work presents the synthesis of five new functionalized\n(benz)imidazolium <i>N</i>-heterocyclic (NHC) ligands (<b>L</b>) and four new\n(benz)imidazole silver(I) NHC (Ag(I)-NHC) complexes of mononuclear <b>[Ag(L)<sub>2</sub>](PF<sub>6</sub>)</b> or binuclear <b>[Ag<sub>2</sub>(L)<sub>2</sub>](PF<sub>6</sub>)<sub>2</sub></b> type.\nThe complexes have been fully characterized, including single crystal\nX-ray diffraction of three new structures. The complexes and their\ncorresponding free NHC ligands have been screened against breast cancer\nand noncancerous cell lines, showing the mononuclear benzimidazole\ncomplex has the highest activity, while the binuclear benzimidazole\ncomplex has the highest cancer cell selectivity. The silver uptake\nwas measured by ICP-MS and highlights a strong link between cytotoxicity\nand cellular uptake. DNA interaction studies, molecular docking, and\nevaluation of reactive oxygen species (ROS) have been conducted for\nthe most promising complexes to identify modes of action. Overall,\nthe binuclear benzimidazole complex is the most selective and promising\ncandidate against the MDA-MD-231 (breast cancer) cell line and has\npotential to be developed for treatment of late-stage breast cancers.