Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium–Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands

An
efficient synthetic protocol was devised for the preparation
of five cationic ruthenium–arene complexes bearing imidazol­(in)­ium-2-dithiocarboxylate
ligands from the [RuCl2­(p-cymene)]2 dimer and 2 equiv of an NHC·CS2 zwitterion. The reactions proceeded cleanly and swiftly in
dichloromethane at room temperature to afford the expected [RuCl­(p-cymene)­(S2C·NHC)]Cl products in
quantitative yields. When the [RuCl2­(p-cymene)]2 dimer was reacted with only 1 equiv of a dithiolate betaine under the same experimental conditions,
a set of five bimetallic compounds with the generic formula [RuCl­(p-cymene)­(S2C·NHC)]­[RuCl3­(p-cymene)] was obtained in quantitative
yields. These novel, dual anionic and cationic ruthenium–arene
complexes were fully characterized by various analytical techniques.
NMR titrations showed that the chelation of the dithiocarboxylate
ligands to afford [RuCl­(p-cymene)­(S2C·NHC)]+ cations was quantitative and irreversible.
Conversely, the formation of the [RuCl3­(p-cymene)]− anion was limited by an equilibrium,
and this species readily dissociated into Cl– anions
and the [RuCl2­(p-cymene)]2 dimer. The position of the equilibrium was strongly influenced by
the nature of the solvent and was rather insensitive to the temperature.
Two monometallic and two bimetallic complexes cocrystallized with
water, and their molecular structures were solved by X-ray diffraction
analysis. Crystallography revealed the existence of strong interactions
between the azolium ring protons of the cationic complexes and neighboring
donor groups from the anions or the solvent. The various compounds
under investigation were highly soluble in water. They were all strongly
cytotoxic against K562 cancer cells. Furthermore, with a selectivity
index of 32.1, the [RuCl­(p-cymene)­(S2C·SIDip)]Cl complex remarkably targeted the erythroleukemic
cells vs mouse splenocytes.