Time-Resolved Spectroscopic Study of the Photochemistry of Tiaprofenic Acid in a Neutral Phosphate Buffered Aqueous Solution from Femtoseconds to Final Products

Abstract

The photo-decarboxylation and overall reaction mechanism of tiaprofenic acid (TPA) was investigated by femtosecond transient absorption (fs-TA), nanosecond transient absorption (ns-TA), and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopic experiments in a neutral phosphate buffered solution (PBS). In addition, density functional theory (DFT) calculations were presented to help interpret the experimental results. Resonance Raman and DFT calculation results revealed that the deprotonated tiaprofenic acid (TPA–) form was the primary species that is photoexcited in a near neutral PBS aqueous solution. The fs-TA experimental data indicated that the lowest lying excited singlet state S1 underwent an efficient intersystem crossing process (ISC) to quickly transform into the lowest lying excited triplet state T1 that then undergoes decarboxylation to generate a triplet biradical species (TB3). ns-TA and ns-TR3 results observed a protonation process for TB3 to produce a neutral species (TBP3) that then decayed via ISC to produce a singlet TBP species that further reacted to make the final product (DTPA). A comparison of the present results for TPA– with similar results for the deprotonated form of ketoprofen (KP–) in the literature was done to investigate how the thiophene moiety in TPA– that replaces one phenyl ring in KP– affects the reaction mechanism and photochemistry of these nonsteroidal anti-inflammatory drugs (NSAIDs).