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.