Computational Studies of the Active Metabolite of Triflusal Molecular Orbitals and Spectroscopic Features; The Basis for Triflusal Phototoxicity Mechanism

Triflusal is a prodrug used as a platelet antiaggregant agent (a platelet aggregation inhibitor). It has efficacy similar to that of aspirin specially in patients with cerebral and myocardial infraction. Chemically, triflusal is nothing except a derivative of acetylsalicylic acid (2-acetyl-3-trifluoromethylsalicylic acid). It is bio-transformed under the effect of a deacetylation process into the active metabolite (known as HTB) which is 2-hydroxyl-3-trifluoromethylbenzoic acid. During the triflusal uses the cutaneous phototoxic/photoallergic side effect is noted including rash, itching or allergic reactions. In order to study this side effect, we use a very excellent tool to study such reactions which is DFT and TD-DFT. The active metabolite of triflusal HTB molecular orbitals and UV-VIS spectroscopic features have been investigated herein. The obtained results show that there is a difference in the molecular orbitals (MOs) pattern between the two forms of HTB (protonated and deprotonated) especially the HOMOs of the deprotonated species. The HOMOs of this species localized on the carboxylic moieties, which is manifested in the Mulliken atomic charge distributions on the carboxylic moiety, where in the deprotonated species shows higher negative charge on carboxylic moieties compared with the neutral form. This is also reflexed in the results obtained for the UV-VIS spectrum of the neutral and deprotonated forms of HTB. The MOs and UV-VIS spectrum of the neutral and deprotonated species of HTB molecule and its excitations to the triplet state are investigated in more details in the present work.