Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

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.

Photocatalytic Modification of Amino Acids, Peptides, and Proteins

“…In PDT, major efforts have been devoted, over the years, to the development of new photosensitizers, with the purpose of increasing light penetration in tissues and to enhance the spatial precision of treatments . An example towards such photosensitizers is the novel organoiridium complex reported by Sadler and co‐workers . The photosensitizer exhibited a long phosphorescence lifetime and allowed the selective induction of cancer cell death in cell cultures by causing oxidative damage on key His residues, which were overexpressed in tumor cells.…”

“…[10a, 60] An example towards such photosensitizers is the novel organoiridium complexr eported by Sadler and co-workers. [61] The photosensitizer exhibited a long phosphorescencel ifetime and allowed the selectivei nductiono fc ancer cell death in cell cultures by causingo xidative damage on key His residues,w hich were overexpressed in tumor cells.…”

Metal–Organic Frameworks Harness Cu Chelating and Photooxidation Against Amyloid β Aggregation in Vivo

“…However, small molecules including thioflavin T derivatives, riboflavin, or porphyrin, are easily aggregated to decrease photooxidative efficiency . In addition, the short lifetime of singlet oxygen ( 1 O 2 ) (<200 ns) as well as the short diffusion distance of 1 O 2 (≈1 μm) also abate their efficiency. Moreover, reactive oxygen species (ROS) can simultaneously destroy normal cells and tissues .…”

Spectroscopic and electrochemical study for evaluating DNA interaction activity of 4‐(3‐halophenyl)‐6‐(pyridin‐2‐yl)pyrimidin‐2‐amine based piano stool Cp* Rh (III) and Ir (III) complexes

“…However, FDA approved Pt drugs includes only three name (cisplatin, oxaliplatin and carboplatin for cancer chemotherapy, due to inappropriate distribution in cell and inactivation by some cellular mechanism . These open up a great scope for researchers of medicinal inorganic chemistry to design and synthesize metallonuclease agents, which can specifically interact with the tumor cell and damage cellular DNA damage by forming metal‐DNA adduct, and a wide range of transition‐metal based biologically active compounds are currently under consideration for future development …”