Despite the well-known effect of electron-withdrawing (EWGs) or electron donating groups (EDGs) on the rate of formation and stability of aromatic EPOs, ANBA, PABA, NABA and PNBA decorated with the same substituents oriented perpendicular to the conjugated cores thus reducing the electronic effect, showed quite divergent calculated Ediss. Hence DFT analysis was further meant to verify if steric interactions could contribute to the overall binding process thanks to the use of 2D and 3D color-filled reduced gradient density (RGD) projections (Figure ). No major differences could be found between the two sets of molecules in the intensity of VdW and steric interactions. However, the aromatic substituents on NABA and PNBA are less tilted compared to the anthracene analogues, lowering the possibilities to establish any interaction and thus resulting in the impossibility to observe such EPOs experimentally. In light of these results, the focus of the predictive analysis was narrowed to the anthracene-based EPOs, seeking for substrates displaying Ediss < 10 kcal mol -1 . 9,10-diphenylalkynylanthracene (DPAA) has been reported to have a half-life (t1/2) of 23 minutes at 25 °C in toluene. Being this value closer to our goal of sustained release of O2 at 37.5°C, its calculated Ediss = 0.88 kcal•mol -1 was taken as lower limit. Moreover, considering the application as therapeutic agents, fully hydrophobic molecules were not taken into consideration, while the presence of hydroxylic, carboxylic and more hydrophilic functional groups was preferred in order to boost their water solubility and/or allow further functionalization. A total of 13 anthracene structures bearing different combination of EDGs or EWGs were tested and compared with DPAA, PABA and ANBA (Table ).