A DF T investigation on the spin–s pin couplings acro ss the hydrogen bon d in no n-steroidal anti-inflammator y propion ic acid derivatives: Iboprofen, Naproxen and Flur biprofen

Ibupro fen [(RS)-۲-(۴-(۲-methylpropyl)p henyl) pro panoic acid ], Naprox en [(+)-(S)-۲-(۶-methoxynaphthale n-۲-yl) pr opanoic acid] and flurbiprofen [(RS)-۲-(۲-fluorobiphe nyl-۴-yl)propanoic acid] (Fig. ۱) a re non-steroidal anti-inflammatory drugs (NSA IDs) that exhibit favorable anti-inflammatory, analgesic and antipyretic prop erties. The major clinical application on NSAIDs is their action as anti-inflam matory agents in muscle skeletal dis eases [۱].In ۲۰۰۶Jubert et al. [۲] p erformed experimental and theoretical studies of Ibuprofen, Naproxen and Tolimetin acid in an effort to el ucidate a more deeper insight on the physic ochemical properties o f NSAIDs. The results showed th at the oxyg en atoms o f the NAIDs would be the preferential site s for the electrophilic attack, am ong them those corresponding to the carboxylic groups. Although th e study of NSAIDs is v ery popular, there are still many unsolved proble ms in the area of the th eoretical study [۳] for it. In this pap er, we decide d to study theoretically the spin–spin coupling constants t o determine the conform ation and t he role of propionic acid to explore whether there is an intramolecular hydrogen bond or not. I n addition, the Bader’s quantum th eory of ato ms in molecules (QTAIM) has also been applied. QTAIM theory per mits to follo w the Lewis standpoin t of a che mical reacti on, to determ ine the ele ctrophilic a nd nucleophilic zones of a molecule from the topolog y and topog raphy of the Laplacian of the charge density, (...) [۴].