The
ruthenium complexes [Ru(CYM)(p-Cl-dkt)(Cl)] (1), [Ru(CYM)(pta)(p-Cl-dkt)]PF6 (2), and [Ru(CYM)(pta)Cl2] (3, RAPTA-C) (CYM = para-
cymene, p-Cl-dkt = 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione, pta = 1,3,5-triaza-7-phosphaadamantane) are biologically active and show anti-
cancer activities, albeit with different mechanisms. To further understand these mechanisms, we compared their speciation in aqueous solutions with an
amino acid (
cysteine), with an
amino acid derivative (
N-acetylcysteine) and with a tripeptide (
glutathione) by Mass Spectrometry (MS). Here, we show that all
ruthenium complexes have high selectivity for
cysteine and
cysteine-derived molecules. On one hand, [Ru(CYM)(p-Cl-dkt)(Cl)] undergoes solvolysis in water and forms [Ru2(CYM)2(
OH)3]+. Subsequently, all
hydroxyl anions are exchanged by deprotonated
cysteine. Infrared Photodissociation Spectroscopy (IRPD) showed that
cysteine binds to the
ruthenium atoms via the deprotonated
thiol group and that
sulfur bridges the
ruthenium centers. On the other hand, the pta-bearing complexes remain monometallic and undergo only slow Cl or p-Cl-dkt exchange by deprotonated
cysteine. Therefore, the
pta ligand protects the
ruthenium complexes from
ligand exchange with water and from the formation of biruthenium clusters, possibly explaining why the mechanism of pta-bearing
ruthenium complexes is not based on ROS production but on their reactivity as monometallic complexes.