Insights into the mechanism of action and cellular targets of ruthenium complexes from NMR spectroscopy.

NMR spectroscopy has proved extremely beneficial in the investigation of inorganic drugs from the time that cisplatin was first introduced into the clinic more than 30 years ago. Both (195)Pt and (15)N NMR were used in early studies and made a major contribution in the understanding of the molecular mechanism of action from model studies involving reactions with amino acids and nucleotides. Over the past decade, ruthenium drugs have proved to be a valuable alternative to platinum drugs, and NMR has also provided unique insights into their molecular mechanism of action including investigations of simple aquation reactions, protein binding and the kinetics and sequence selectivity of DNA binding interactions. In this article, emphasis is given to define the cellular targets and elucidate some of the mechanistic profiles of recent ruthenium-based organometallic compounds offering efficacy toward cancer cells, by various NMR techniques.