Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells.

Pingyu Zhang,Hui Chao,Huaiyi Huang,Thomas Malcomson,Peter B O'Connor,Cookson K C Chiu,Abraha Habtemariam,Martin J Paterson,Yuko P Y Lam,Peter J Sadler,Guy J Clarkson

doi:10.1002/anie.201709082

Abstract

Strongly luminescent iridium(III) complexes, [Ir(C,N)2(S,S)]+ (1) and [Ir(C,N)2(O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X‐ray crystallography and DFT calculations. Their long phosphorescence lifetimes in living cancer cells give rise to high quantum yields for the generation of 1O2, with large 2‐photon absorption cross‐sections. 2 is nontoxic to cells, but potently cytotoxic to cancer cells upon brief irradiation with low doses of visible light, and potent at sub‐micromolar doses towards 3D multicellular tumor spheroids with 2‐photon red light. Photoactivation causes oxidative damage to specific histidine residues in the key proteins in aldose reductase and heat‐shock protein‐70 within living cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of enzymes involved in the glycolytic pathway.

Highlights

Luminescent iridium(III) complexes, [Ir(C,N)2(S,S)]+ (1) and [Ir(C,N)2(O,O)] (2), containing C,N, O,O, or S,S chelating ligands, have been characterized by X-ray crystallography and DFT calculations
Absorption of light by a photosensitizer promotes formation of a triplet state which can polarize the spins of the ground-state 3O2 to generate highly toxic 1O2
Surface cancers are accessible to photodynamic therapy (PDT), but light can be directed to a range of other tissues using, for example, fiber optics

Summary

Introduction

Luminescent iridium(III) complexes, [Ir(C,N)2(S,S)]+ (1) and [Ir(C,N)2(O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X-ray crystallography and DFT calculations. The photoactivation in cancer cells leads to specific oxidative damage in some key cellular proteins.

Results

Conclusion