Autocatalytic-Assisted Photorelease of a Sensitizer Drug Bound to a Silica Support

Abstract

The photorelease of a sensitizer from a fluorinated silica surface occurs by a reaction of singlet oxygen with the vinyl ether bond linking with scission of a dioxetane intermediate. Irradiation of the released sensitizer generates singlet oxygen, which accelerates the release of more sensitizer via an autocatalytic reaction. Sigmoidal behavior of sensitizer release in n-butanol and n-octanol occurs at the optimal temperature of 20 °C. The photorelease efficiency was reduced at low temperatures, where the sensitizer was retained on the surface due to a long-lived dioxetane with inefficient scission; and also reduced at high temperatures, due to a slower reaction of 1O2 with the vinyl ether bond. Immediate acceleration is a result of released sensitizer being used as a dopant to eliminate the induction step further implicating an autocatalytic mechanism. However, the sigmoidal sensitizer release was not correlated to solvent viscosity, heat or light from the dioxetane decomposition, or to minor O2 solubility enhancements caused by the fluorinated silica. The mechanistic information collected here can be used to help control the pace of drug release; however, it remains to be seen whether an autocatalytic-based drug delivery system has an advantage to those with non-sigmoidal kinetics.

S,S‐Chiral Linker Induced U Shape with a Syn‐facial Sensitizer and Photocleavable Ethene Group

“…. In contrast, previously reported sensitizer–ethene dimers contain no such bending group and are thought to adopt linear conformations due to their dimethylene or succinate connecting groups.…”

“…The results shown in Table (entry 1) indicate a low sensitizer photorelease efficiency of 5% after 1 h of irradiation at 669 nm, as determined by monitoring the appearance of the released sensitizer's Q‐band absorption in n ‐butanol. The sensitizer photorelease efficiency increased substantially (68–99%) with a dimethylene or succinate linker (Table , entries 2–4) . A previous report also showed the optimal photorelease rate was obtained with sensitizer loading of 4.4 μmol g −1 silica and a sensitizer‐to‐sensitizer distance of 17 nm (Table , entry 2).…”

“…A photoreleasable sensitizer has been successfully synthesized and attached to silica using a chiral (1 S ,2 S )‐cyclohexane‐1,2‐dicarboxylate linker. The observed ~19‐fold decrease in sensitizer loading, as compared to similar sensitizers bearing succinate or dimethylene linkers , can be attributed to a key problem. Namely, a bend in the S,S ‐linkage is found to hinder the sensitizer silane from coupling to the silica surface.…”

“…We hypothesized that the U shape of the bridge would increase the exposure of the ethene site for enhanced 1 O 2 ‐based sensitizer release. We expected this system to be an improvement over our previous succinate and dimethylene‐linked sensitizer photorelease systems. In this system, the 1 O 2 , which triggers the sensitizer release, is generated by the sensitizer surface.…”

Fluorinated Photodynamic Therapy Device Tips and their Resistance to Fouling for In Vivo Sensitizer Release

“…Lastly, we now know there is a complimentary effect where the fluorinated tip 1 not only repels biofoulants better, it also suppresses surface 1 O 2 physical quenching for a more efficient sensitizer photorelease. It could be argued that added biofouling protection results from the production of 1 O 2 at the surface of tips 1 and 5 as has been observed for other surfaces which produce 1 O 2 or ROS .…”