New mechanistic insights into osmium-based tamoxifen derivatives

Highlights: • Electrochemical behavior of an organometallic osmium-based anticancer drug candidate. • Mechanistic investigations by cyclic voltammetry. • Evidence of a stable quinone methide carbocation intermediate. -- Abstract: The electrochemical behavior of osmociphenol (3, Oc-OH), an organometallic osmium-based anticancer drug candidate, has been investigated by cyclic voltammetry in the absence and presence of lutidine used as a base model. Osmociphenol exhibited spontaneous deprotonation of the phenol function upon oxidation of the osmocene moiety due to its high acidity. In the presence of lutidine, a base-dependent and different electrochemical behavior was observed at low scan rates indicating a second oxidation step leading to the corresponding cationic quinone methide precursor (3b⁺). However, compared to ruthenocene derivatives, the stability of 3b⁺ prevented its conversion into quinone methide as the final and stable complex. Despite differences in their oxidative processes, osmociphenol and ruthenociphenol derivatives exhibit similar biological activities.