JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.138, no.34, pp.10968 - 10977
Abstract
Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen (O-1(2)) and superoxide radical (O-2(center dot-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT). have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (<= 1 J cm(-2)) because of the relatively high O-1(2) quantum yield (> 0.78), even with two photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria) producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexpi.