Ruthenium coordination compounds of biological and biomedical significance. DNA binding agents

Ruthenium complexes exhibit a broad variety of biological and biomedical activities including anticancer efficiency. The reason is that the octahedral bonding of both Ru(II) and Ru(III) complexes affords an extensive repertoire of three-dimensional architectures, giving the potential for a high degree of site selectivity for binding to their biological targets. The mechanism of biological and biomedical action of ruthenium compounds is connected with their interactions with biomacromolecules. A lot of mechanistic studies revealed disposition of many ruthenium complexes to operate via mechanisms of action involving interactions with DNA, but distinctly different from those of the approved platinum anticancer drugs. In this Review, we discuss major DNA binding modes hitherto identified for ruthenium complexes of biological or biomedical significance and provide some typical examples. The introduction provides the reader with a brief overview of the approaches in the search for the new, transition metal-based agents of biological or biomedical significance to provide the context in which more recent research of DNA binding of ruthenium complexes has been evolved. We then describe main categories of binding modes between DNA and ruthenium compounds, such as coordinative, intercalative, minor groove binding, sequence specificity of DNA binding, the ability of ruthenium compounds to condense and cleave DNA, binding to A- and Z-DNA, DNA quadruplexes and other unusual DNA structures. A number of complexes based on ruthenium(II) centers have been reported to have excellent photophysical and radiosensitizing properties so that DNA photocleavage and synergistic enhancement of DNA damage due to a combined action of ruthenium complexes and ionizing radiation is also discussed. Finally, inhibition of DNA processing enzymes is reviewed as well. We believe that such a synthesis of disparate DNA binding modes of ruthenium complexes will help to generate new ruthenium complexes of improved biological and biomedical significance.