Controlling the Reactivity of Ruthenium(II) Arene Complexes by Tether Ring-Opening

The closed- and open-tethered RuII η6-arene complexes [RuII(η6:η1-C6H5(C6H4)NH2)(en)]Cl2 (2) and [RuII(η6-C6H5(C6H4)NH2)Cl(en)]Cl (3), where en is ethylenediamine, have been synthesized and their X-ray structures determined. Interconversion between 2 and 3, that is, tethered-arene ring-closure and ring-opening, in different solvents has been investigated. Complex 2 opens in dimethylsulfoxide (DMSO) by solvent-induced dissociation of the NH2 group of the pendant arm. In methanol, however, equilibrium between 2 and 3 is reached after 12 h when both species coexist in solution in a ratio of 2:1 (open/closed). In water (pH 7), complete ring closure of 3 to 2 at 298 K occurs in less than 2 h. The tether ring of complex 2 opens at basic pH and closes at neutral pH. Complex 2 opens over time (18 h) in concentrated HCl. The opening-closing process is fully reversible in the pH range 2−12. Density Functional Theory calculations have been used to obtain insights into the electronic structure of complexes 2 and 3, their UV−vis properties, and their stability compared to their aqua derivatives. Control of tether-ring-opening can contribute toward a strategy for activation and for achieving cytotoxic selectivity of ruthenium arene anticancer drugs.