Aminocarbyne-Alkyne Coupling in Diruthenium Complexes: Exploring the Anticancer Potential of the Resulting Vinyliminium Complexes and Comparison with Diiron Homologues.

ABSTRACT

New diruthenium complexes based on the scaffold Ru2Cp2(CO)2 (Cp = η5-C5H5) and containing a bridging vinyliminium ligand, [2a-d]CF3SO3, were synthesized through regioselective coupling of alkynes with an aminocarbyne precursor (85-90% yields). The reaction involving phenylacetylene proceeded with the formation of a diruthenacyclobutene byproduct, [4]CF3SO3 (10% yield). Complexes [2a-d]+ undergo partial alkyne extrusion in contact with alumina or CDCl3. All products were characterized by elemental analysis, infrared and multinuclear NMR spectroscopy, and single crystal X-ray diffraction in two cases. Complexes [2a-d]+ revealed an outstanding stability in DMEM cell culture medium at 37 °C (<1% degradation over 72 h). These complexes exhibited cytotoxicity in human colon colorectal adenocarcinoma HT-29 cells in the low micromolar range, with lower IC50 values than those obtained with the homologous diiron complexes previously reported. Evaluation of ROS (reactive oxygen species) production and O2 consumption rate (OCR) highlighted the higher potential of Ru2 complexes, compared to the Fe2 counterparts, to impact mitochondrial activity, with the heterometallic Ru2-ferrocenyl complex [2d]+ showing the best performance.