NMR Studies of Metallointercalator–DNA Interactions

The study of the interaction between inert transition metal complexes and nucleic acids has developed from the early work of Dwyer [1], Lippard [2], Norden [3] and Barton [4] to the point that it is now a central theme in bio-inorganic chemistry. While there has been considerable interest in metal complexes that bind nucleic acids, the interaction of metallointercalators with DNA and RNA has received the most attention [5, 6]. Square-planar platinum(II) complexes have demonstrated significant anticancer activity [7], and octahedral ruthenium(II) and rhodium(III) complexes have been used as probes of nucleic acid structure and as a means to study electron transfer reactions mediated by the heteroaromatic bases [5, 6]. While a range of techniques is available to study the nucleic acid binding of metal complexes, NMR spectroscopy (particularly 1H NMR) has proven to be the most useful. NMR spectroscopy can provide a detailed, atom level resolution, picture of the metal complex binding, and if the quality of the data is sufficient, a threedimensional structure of the metal complex bound to the oligonucleotide can be determined. The strategies used to assign the 1H NMR spectrum of an oligonucleotide [8–10], the extension of these methods to study the interaction of metal complexes with DNA and the use of molecular modelling will be presented in this chapter.