Transition metal complexes as probes of nucleic acids

Abstract

This chapter discusses a series of transition metal complexes that recognize the nucleic acid binding sites based on shape selection. By matching the shapes and symmetries of the metal complexes to particular variations in local nucleic acid conformation, a family of molecules that target different DNA sites have been developed. The recognition of a site depends on the local conformation, or shape, rather than on the sequence directly. Indeed, based purely on such considerations of shape and symmetry, a high level of specificity may be achieved. The molecules prepared serve as a novel series of conformation-selective probes, and these may be utilized to map the topological variations in structure along the nucleic acid polymer. The chapter also discusses the sequence-neutral cleavage complex, Rh(phi)^2bpy^(3+) (where bpy is bipyridine), a useful reagent for high-resolution photofootprinting, as well as several conformation specific tools to examine nucleic acid structure. These various ruthenium and rhodium complexes may be applied to detect subtle variations in B-DNA conformations or to investigate global secondary structures of a polynucleotide such as DNA cruciforms, left-handed Z-DNA, and A-form DNA. The chapter describes the way the secondary and tertiary structure of RNA may be examined using this methodology. The different information that may be gained from these methods is also discussed. In general, studies with these complexes provide a unique and sensitive handle to probe elements of nucleic acid polymorphism in solution.