Water-soluble arene ruthenium complexes: From serendipity to catalysis and drug design

• The history of water-soluble arene ruthenium complexes is retraced.
• Such complexes activate hydrogen and are catalysts or catalyst precursors in water.
• Bioconjugates and anticancer can be developed with such complexes.

Shortly after the discovery of benzene ruthenium dichloride and some controversy about its polymeric or dimeric nature in the 1960s, the hydrolysis of this material in water to give a mixture of benzene ruthenium aqua complexes was discovered. However, it took a long time until this reaction and the hydrolysis of other arene analogs were used as an entry to the synthesis of water-soluble arene ruthenium complexes. These complexes are able to activate molecular hydrogen in aqueous solution and allow the design of arene ruthenium bioconjugates. They can serve as catalysts or catalyst precursors for hydrogenation and transfer hydrogenation reactions in water and they are at present one of the most promising classes of metal complexes to replace cisplatin in future cancer therapy, due to their inherent cytotoxicity and their good cellular uptake, conditioned by well balanced lipophilic and hydrophilic properties.

Many arene ruthenium complexes can be handled in water thanks to the surprising inertness of the arene ruthenium bond towards hydrolysis. Arene ruthenium chloro complexes can undergo aquation to give cationic aqua complexes that are water-soluble. This historical perspective retraces the evolution of this field from the chance discovery to topical research in catalysis and drug design.Figure optionsDownload as PowerPoint slide