Naphthalene Endoperoxide Heterodimer Designed for Sustained Singlet Oxygen Release

Abstract

Naphthalene endoperoxides undergo thermal cycloreversion reactions to produce singlet oxygen and their parent naphthalene compounds. The rate of the reaction is dependent on the structural features, such as steric and electronic modulators. We believe that achieving a sustained release rate of singlet oxygen is important in potential biological applications. This can be achieved by tethering of two endoperoxides with different singlet oxygen release rates in a single molecular construct. Here, we report the synthesis of such a dimeric endoperoxide. Our data shows that with the biexponential reaction kinetics of singlet oxygen generation from a heterodimeric endoperoxide, it is possible to hold singlet oxygen release rates within a selected range for a longer period of time.

Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment

“…IR820, 3-amino-1-propanol, and triethylamine (dissolved in anhydrous DMF, molar ratio 1:2:4) were added sequentially to a 50 mL round bottom flask and stirred for 4 h at 85 °C with nitrogen protection and aluminum foil shade (500 rpm). After the reaction was completed, the solvent (anhydrous DMF) was removed by rotary evaporation to obtain IR820 hydroxylated crude product (IR820-OH), which was then purified by silica gel column chromatography [ 54 ]. The resultant IR820-OH is scraped and weighed to calculate the molar mass.…”

Oxygen-Generating Biomaterials for Translational Bone Regenerative Engineering

“…189 However, the half-life of endoperoxides can be controlled by methods like steric modification. 190 Endoperoxides have already been used in biomedical applications. Lu et al fabricated a covalent organic framework (COF) comprised of endoperoxide for cancer treatment.…”

“…Third, endoperoxides have a short half-life, which is inappropriate for long-term oxygen generation . However, the half-life of endoperoxides can be controlled by methods like steric modification . Endoperoxides have already been used in biomedical applications.…”

Aromatic Endoperoxides†

“…Example 6 (Eq. 4) illustrates the formation of a bisendoperoxide, 12 (25). Singlet oxygen carriers with multiple endoperoxide functional groups, such as 12, can be used to gain temporal control (25)(26)(27)(28)(29)(30) over the release of singlet oxygen.…”

“…4) illustrates the formation of a bisendoperoxide, 12 (25). Singlet oxygen carriers with multiple endoperoxide functional groups, such as 12, can be used to gain temporal control (25)(26)(27)(28)(29)(30) over the release of singlet oxygen. An optimal release rate of singlet oxygen in biological systems (temporal control) is important because dominant quenching by glutathione is observed at slow-release rates and cytotoxic effects are observed at high singlet oxygen release rates (31).…”