A Click Chemistry Approach for Developing Organelle-Directed Photocytotoxic Ruthenium(II) Probes

Transition metal complexes are versatile probes for cellular imaging and sensing. While the interactions of Ru(II) polypyridyl complexes with macromolecules such as DNA have long been studied, their application in cells or tissues has been limited by poor membrane permeability. Here, we report Ru(II) probes coupled to a membrane-permeable triphenylphosphonium (TPP) vector. The biocompatible conjugation was achieved through click chemistry of an azide-functionalized polypyridyl ligand with an alkyne-modified TPP moiety. Evidence of cellular localization, predominantly in the mitochondria, was de-rived from live-cell confocal fluorescence microscopy. The ability of TPP-modified Ru(II) conjugates to intercalate DNA, and hence serve as molecular beacons, was identified. Spectroscopic solution studies and fluorescence imaging revealed that complexes containing a TPP-1,10-phenanthroline (TPP-phen) ligand act as more potent luminescent probes than those with a TPP-dipyridophenazine (TPP-dppz) ligand, thereby highlighting the importance of probe design to biological application.