Trifluoromethyl Gold(I) Isonitrile Complexes: Synthesis, Structures and Cytotoxicity

ABSTRACT A series of trifluoromethyl gold(I) complexes supported by isonitrile or phosphine ligands has been synthesized and fully characterized. Single‐crystal X‐ray diffraction analysis revealed a diverse landscape of supramolecular architectures in the solid state, including one‐dimensional chains, discrete dimers, and monomers, primarily governed by aurophilic (Au···Au distances: 3.086–3.958 Å) and π‐hole isonitrile ···F–CF 2 interactions. Theoretical calculations (QTAIM and NCI) confirmed the attractive nature and cooperativity of these noncovalent networks. In general, gold(I) complexes show anticancer potential, yet gold(I)–CF 3 versions for medicinal benefits are completely unexplored biologically. In this work, the in vitro antiproliferative activity was evaluated against cisplatin‐sensitive (A2780) and cisplatin‐resistant (A2780cis) ovarian carcinoma cells, as well as nonmalignant (HEK293) cells. Several complexes exhibited exceptional submicromolar potency, significantly outperforming cisplatin. The standout compound, complex 2 , exhibited a remarkably low resistance factor (1.4), demonstrating a pronounced ability to overcome cisplatin resistance. This constitutes the first combined structural and biological investigation of such systems, establishing a novel and fertile niche for the future application of gold(I)–CF 3 complexes.