Photoinduced Storage and Thermal Release of Singlet Oxygen from 1,2‐Dihydropyridine Endoperoxides

Abstract

The quest for molecules able to trap, store, and release singlet oxygen is of utmost interest due to their applicability in various domains such as materials science and photomedicine. The aim of this study was to prepare and study a new family of singlet oxygen donors based on the 1,2‐dihydropyridine motif. The experiments demonstrated the influence of substituents and solvents on the photooxygenation rate constants. The process can be operated reversibly by thermolysis of the in situ formed endoperoxide leading to a release of singlet oxygen and formation of the parent 1,2‐dihydropyridine compound. A bifunctional structure based on a phenalenone photosensitizer covalently connected to a 1,2‐dihydropyridine module was synthesized via a multi‐step sequence. Upon irradiation with blue light, singlet oxygen was produced leading to the formation of the endoperoxide intermediate. In the dark cycle, the endoperoxide underwent cycloreversion reaction affording the parent 1,2‐dihydropyridine unit paving the way to a continuous production of singlet oxygen during the light/dark cycles.

Dark Dynamic Therapy: Photosensitization without Light Excitation Using Chemiluminescence Resonance Energy Transfer in a Dioxetane–Erythrosin B Conjugate

“…18,19 Moreover, 1,2-dihydropyridine endoperoxides have recently been demonstrated as efficient singlet oxygen storage and release compounds as well. 20 As a proof-of-principle, we sought to develop a watersoluble, cell-permeable small molecule that can produce singlet oxygen without light excitation (i.e., dark dynamically) capable of killing cancer cells without requiring addition of exogenous agents. To this regard, we are using Schaap's chemiluminescent (CL) scaffold (Figure 1).…”

“…Although singlet oxygen was produced without irradiation, cancer cell death was not demonstrated. Finally, the thermal decay of singlet oxygen release from 2-pyridone endoperoxides has been shown as a promising alternative to luminescence. , However, to date, cell killing has only been described for hypoxic conditions, while normoxia required the addition of exogenous fluoride to enhance singlet oxygen release. , Moreover, 1,2-dihydropyridine endoperoxides have recently been demonstrated as efficient singlet oxygen storage and release compounds as well …”

Photosensitizer-singlet oxygen sensor conjugated silica nanoparticles for photodynamic therapy and bioimaging

“…An array of uorescence (FL) probes built on polycyclic and heterocyclic aromatics has been developed to detect or sense 1 O 2 . [7][8][9][10][11][12] However, the performances of such probes are limited due to inadequate FL turn-on features, low sensitivity, and complex syntheses. Nevertheless, anthracene derivatives dominate as safe 1 O 2 sensors and carriers, and substituents at the 9,10positions of anthracene modulate the 1 O 2 sensitivity.…”

Unsymmetrical Anthracene Platforms as Singlet Oxygen Batteries: Effects of Substituents on Photooxygenation and Endoperoxide Thermolysis

“…[14] However, these studies remain limited to a single derivative in each report, and the impact of the substituents on the photooxygenation and the cycloreversion has never been explored with unsymmetrical 9,10-disubstituted anthracenes. As part of our ongoing research into the development of singlet oxygen batteries, [15] we detail the synthesis and the properties towards singlet oxygen of a selection of 9,10-disubstituted anthracenes bearing (hetero)arylalkyne and (hetero)aromatic substituents with different electronic properties (Figure 1). Notably, the photooxygenation generates relevant aromatic endoperoxides for applications as singlet oxygen sources.…”