Singlet dioxygen (1O2) has capacity to readily undergo Diels-Alder type cycloaddition reactions with a variety of biological dienes, including nucleosides. Such reactivities may serve as a key principle of photodynamic treatments of epidermal cancer. However, little is known about the molecular mechanism, by which 1O2 causes cell death. To enable the mechanistic studies, molecular tools for 1O2 are essential. This prompted us to create a series of molecules that generate and respond to 1O2. Molecular dyads consisting of an organoiridium complex and a coumarin fluorophore having a julolidine unit was prepared. The Ir(III) complex moiety was capable of photosensitization 1O2 at a quantum yield as high as 100%. We found that 1O2 mediated dehydrogenative iminium formation of the coumarin component. Control experiments performed in the presence of 1O2 scavengers supported 1O2 specificity of the reaction. The oxidation reaction accompanied fluorescence ratiometric responses, serving a viable strategy for detection of 1O2. The dual photofunctionalities have been demonstrated using macrophages and mammalian cancer cells. The cellular experiments revealed that the 1O2 provoked apoptosis at the early stage of photoirradiation, while prolonged exposure to 1O2 led to necrosis. This study is suggestive of a signaling action of biological 1O2. To expand photobiological utility, 1,3-diphenylisobenzothiophene (DPBS) was prepared through a two-step synthesis from 1,3-diphenylisobenzofuran. DPBS reacted slowly with photogenerated 1O2 to form unstable endoperoxide, which is subsequently hydrolyzed into 1,2-dikitone. The latter step released hydrogen sulfide (H2S), an important gasotransmitter. We explored the 1O2-mediated photo-uncaging reaction of H2S. The studies demonstrated that the reaction can serve a useful strategy for photocontrolled delivery of H2S.

Molecular approaches to photocontrol of biological singlet dioxygen

253rd National Meeting (2017)

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