The development of new photosensitizers for photodynamic therapy (PDT) continues unabated, both with regard to new chemical structures, formulations and as nanomaterials. Yet, less attention is given to the photochemical pathways by which singlet oxygen and other reactive oxygen species (ROS) are generated. Normally, photosensitizers exert their action in the light through generation of singlet oxygen and other ROS and their production ceases in the dark. Thus, standard PDT as a photo-therapy couples illumination and singlet oxygen generation. Yet, it is possible to do “PDT” in the dark. This requires the initial (photochemical) generation of singlet oxygen, storage in chemically stable form, and then later release via a chemical reaction. Such chemodynamic therapy (CDP) approaches can be coupled with the photochemical generation and spatial and temporal control of singlet oxygen using the reversible formation of aromatic endoperoxides. Singlet oxygen generation upon decomposition of endoperoxides at ambient temperatures represents an alternative to classical PDT, which is limited by hypoxia and reduced light penetration into cancer tissue. The concept will be illustrated using pyridone-porphyrins and heavy atom-free BODIPY-anthracene dyads, which produce triplet excited states from charge-separated excited states formed via photo-induced electron transfer. Their interaction with molecular oxygen results in efficient 1O2 generation and is accompanied by formation of highly fluorescent species due to cycloaddition of 1O2 to the anthracene subunit. ROS generation from these systems in living cells induces cytotoxicity and at the same time provides fluorescent visualization of the dyads, promising new therapeutic and imaging applications. Next to offering a new approach in photomedicine these electron donor-acceptor dyads exhibit unique photochemical characteristics, notably with regard to controlling the triplet state generation by media polarity and structural factors.

Organic endoperoxides: Storing and releasing singlet oxygen

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.