Herein, computational and crystallographic data were used to select the most suitable structural features to improve the ORA performances in terms of EPO formation and O2 release. For the first time, the synthesis of anthracene-based EPOs bearing carefully selected substituents was carried out using a continuous flow photochemical reactor allowing to envisage the industrial scale up of the photooxygenation step (Figure ). Importantly, as anticipated by computational insights, these EPOs release O2 in physiologically compatible conditions thus suggesting the possibility to further explore these molecules as ORAs for relieving hypoxia.