Translation of photooxygenation reaction of aromatic molecules from organic to aqueous environment: challenges towards a preparative protocol

With the aim of developing green synthetic protocolsfor the photooxygenation of hydrophobic molecules in water, a combination of supramolecular and photo-chemistrieswas exploited.The photochemical synthesis of aromatic endoperoxides is a very well-known and established procedure for the storage of molecular oxygen to be exploited in situin biological applications. In fact, the mechanism bringing to the formation of this bridge is reversible and tunable, enabling the release of molecular oxygen or reactive oxygen species (ROS) according to the molecular structure.We optimized the photochemical synthesis of selected aromatic endoperoxidesin organic solventsin the presence of a photosensitizer, i.e.Methylene Blue (MB), catalyzing the covalent link of singlet oxygen (1O2) onto the aromatic backbone. The same reaction was then translated to aqueous environment after inclusion complexation of the substrates and MB in a cyclodextrin-based polymeric network. The same performance was achieved in the same reaction conditions, allowing the application of a greener procedure for upscaling. The release of 1O2and ROSwas achieved by thermolysis of the formed endoperoxide bridges irrespectively of the environment in which they were obtained and subsequently heated. These preliminary results pave the way for future development of photodynamic therapy (PDT) in hypoxic conditions, i.e.when inside solid cancer cells it is not achieved an adequate supply ofO2, reducing the standard PDT efficacy.