Chiral Resolution of Transition Metal Polypyridyl Complexes via HPLC As a Gateway to Enantiopure DNA Targeting Probes

The intrinsic structural and photophysical properties of octahedral tris-(bidentate) transition metal polypyridyl complexes make them attractive DNA probes whose binding affinity and specificity for DNA can be greatly influenced by the Δ- and Λ-enantiomer forms. Strategies for chiral resolution include chiral precursors, fractional crystallisation with chiral salts as well as chromatographic methods. The present work details the optimisation of a chiral resolution process to facilitate the isolation of metal complex enantiomers via chiral stationary phase HPLC using a semi-preparative column. The scope of the study includes both Ru(II) and Os(II) polypyridyl enantiomers containing commonly encountered coordination environments as well as a range of more exotic ligand scaffolds that illustrate the generality of the method. Notably, this work also describes the ability to separate enantiomers of a mixture of two complexes prepared as a result of ‘ligand-scrambling‘ during synthesis.