Lipophilic ruthenium complexes with tuned cell membrane affinity and photoactivated uptake

Abstract

Ruthenium dipyridophenazine (dppz) complexes are virtually non-emissive in aqueous solutions but show strong luminescence in hydrophobic environments, making them interesting as molecular probes in cellular imaging. We show by luminescence spectroscopy that by substituting the dppz ligand with alkyl ether chains of increasing length the complexes can be tuned from preferential intercalation into DNA to insertion in model phospholipid membranes. Confocal laser scanning microscopy (CLSM) on methanol fixed CHO-K1 cells show an analogous distribution in the cell, where the least hydrophobic complex exclusively stains the nucleus whereas the more hydrophobic ones seem to predominantly stain membrane structures in the cytoplasm. In live cells CLSM show that initially only the more hydrophobic derivatives stain the plasma membrane. However, brief further exposure to the laser light causes permeabilization of the membrane and accumulation of extracellular ruthenium complexes in internal cellular structures, similarly to the distribution found in fixed cells.