Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways

Abstract

The cellular response evoked by antiproliferating osmium­(VI) nitrido compounds of general formula OsN­(N^N)­Cl₃ (N^N = 2,2′-bipyridine <b>1</b>, 1,10-phenanthroline <b>2</b>, 3,4,7,8-tetramethyl-1,10-phenanthroline <b>3</b>, or 4,7-diphenyl-1,10-phenanthroline <b>4</b>) can be tuned by subtle ligand modifications. Complex <b>2</b> induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, <b>4</b> evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, <b>4</b> is the first osmium compound to induce ER stress in cancer cells