Computational Study of Photodegradation Mechanism of Alminoprofen, The Basis for Designing New NSAIDs

Alminoprofen (AP) is 2-(4-((2-methlyallyl)amino)phenyl)propanoic acid, or 2-[4-(2-methylprop-2-enylamino)phenyl]propanoic acid. It has a role as a lipoxygenase, a phospholipase A2 and a cyclooxygenase 2 inhibitor. Due to these enzyme’s inhibitions, it is used as anti-inflammatory, anti-rheumatic and anti-pyretic agent in treatment of inflammatory and rheumatic disorders. Because of the AP is belonging to the propionic aromatic acid structure derivatives and is very similar to the ibuprofen molecule and due to the photosensitivity adverse effects related to this group, the present work focuses upon the photosensitivity photodegradation mechanism of AP. This has been done using the HF-DFT/TD-DFT framework by applying the hybrid functional B3LYP level of theory. Similar to other NSAIDs studied previously, the obtained results of AP from the computed energies and properties of various species show that the deprotonated form dominates at physiological pH, is the susceptible species for photodegradation more than the neural form. In addition, the former species will not be able to decarboxylate from a singlet excited states with high efficiency. In contrast, after it undergoes intersystem crossing, the excited triplet state of the deprotonated form will decarboxylate, with very high efficiency. Molecular orbitals, energies of various species, various energy barriers, reactive radical species, the reactions of radical species with macromolecules and more throughout alminoprofen photodegradation mechanism have been discussed in more details in this work.