In the frame of the HypoCyclo project, cyclodextrin-based polymers (BCDPS) are aimed to be used as suitable shuttle for the delivery of a combination of therapeutic agents as a novel treatment for breast cancer. Together with a chemotherapeutic drug and a photosensitizer (PS) to implement photodynamic therapy (PDT), the project aims to co-encapsulate an Oxygen-Releasing Agent (ORA) as biocompatible vector to supply molecular oxygen (O2) in tissues for the recovery of hypoxic conditions (low O2 tension).
Aromatic endoperoxides are gaining appeal as ORAs, since they are cheap and versatile substrates able to reversibly bind and release O2. The synthesis of these substrates has been conveniently optimized in organic solvent in the presence of methylene blue as cheap PS for the selective production of the reactive species 1O2. However, forecasting a future scale-up based on a greener synthetic approach, a photocatalytic process was designed and developed exploiting BCDPS in homogeneous aqueous phase.
A very hydrophilic βCD polymer crosslinked with epichlorohydrin has been used to effectively solubilize the aromatic substrates in the mM range and catalytic amounts of the PS in buffered water thus enabling, upon suitable irradiation, selective photooxygenation, straightforward isolation of the target endoperoxides and full recovery of the polymeric matrix. Notably, promising conversion of the substrates was achieved in non-deuterated solution for the first time, an extraordinary result considering the very short lifetime of 1O2 in such solvent. Clean and smooth cycloreversion of one anthracene-based ORA was achieved in the reaction mixture, suggesting the use of a unique BCDPS platform performing simultaneously as solubilizing agent, inert reaction vessel and delivery system for the synthesized ORA.
A Cyclodextrin Polymer as Supramolecular Matrix for Scalable Green Photooxygenation of Hydrophobic Substrates in Homogeneous Phase – M. Agnes, A. Mazza, E. Kalydi, S. Béni, M. Malanga and I. Manet, Chem. Eur. J. 2023, e202300511. DOI: https://doi.org/10.1002/chem.202300511