Targeting nucleic acids with metal complexes is an exciting and widely explored field of research. Following the discovery of the anticancer drug cisplatin, a number of metal complexes have been designed, synthesised, and tested for their DNA binding properties. On the contrary, the interaction of metal complexes with RNA has been much less investigated. RNA is an essential biomolecule, involved in a variety of crucial cellular functions, which offers a much wider structural diversity than DNA. As such, RNA represents an attractive target for the design and the development of structure-selective therapeutic and diagnostic agents. A few recent publications describe the ability of various metal complexes to interact with RNA, and the binding of cisplatin and derivatives to RNA is being currently investigated. This short review offers an overview of some recent advances on both covalent and non-covalent interactions of metal complexes with RNA and addresses the potential of targeting RNA non-duplex structures.

Studying the interaction of metal ions with RNA is challenging because of the fast dynamics of the system and the intricate interplay between structural and functional roles of metal ions. NMR spectroscopy is an exceptional tool to investigate such interactions in solution and allows for a detailed description of both metal ion binding sites and binding modes in complex and dynamic RNA structures. We recently applied heteronuclear NMR to study the metal ion binding properties of a three-way junction RNA (D1κζ) which plays an important role in group II intron splicing, and observed metal ion binding in both κ and ζ regions of the construct. Here we concentrate in more detail on the ζ region (D1ζ) using NMR to investigate the interaction with Mg(II), Cd(II) and cobalt(III)hexammine. Our data confirm Cd(II) induced macrochelate formation at the 5ʹ-end triphosphate, suggest an overall similar behaviour for the two divalent metal ions, but with much clearer changes in chemical shifts upon Cd(II) addition, and reveal only little changes upon cobalt(III)hexammine addition, allowing to discriminate between inner-and outer-sphere binding. Moreover, we observed distinct differences when we titrated the sample with Cd(II) in the presence of either KCl or KClO 4 as background monovalent salt.