Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province , Shantou University , Shantou 515063 , China.
Chem Res Toxicol. 2019 Apr 15;32(4):613-620. doi: 10.1021/acs.chemrestox.8b00310. Epub 2019 Feb 15.
Naproxen is a nonsteroidal anti-inflammatory drug that exhibits phototoxic side effects in humans, but its mechanism of phototoxicity is ambiguous. To uncover photophysical and photochemical reaction processes of naproxen, femtosecond to nanosecond transient absorption spectroscopies were employed to directly detect excited and transient states of naproxen upon UV irradiation in pure acetonitrile, acetonitrile:water 1:1, and acetonitrile:PBS 1:1 solutions. The transient absorption data together with time-dependent density functional theory analysis-predicted absorption spectra of selected intermediates were integrated to elucidate photochemical mechanisms for reactions of naproxen in different solutions. Femtosecond transient absorption results demonstrated that naproxen has two different photochemical pathways at the early delay time before the formation of final products in various solutions. In a pure acetonitrile solvent, naproxen undergoes charge transfer to solvent to generate a radical cation intermediate, which decarboxylates to generate a radical B intermediate. While in an acetonitrile:PBS 1:1 solution, naproxen predominantly deprotonates first and is promoted to the singlet exited state (NPX), which undergoes intersystem crossing to give rise to the lowest-lying triplet states (T). T then undergoes decarboxylation reaction and produces a radical B species. Kinetic characterization of these processes reveals that the decarboxylation reaction in an acetonitrile:PBS 1:1 solution is faster than that in a pure acetonitrile solvent. Deep studies on photophysical and photochemical processes of NPX will aid us to better understand the toxicology mechanisms associated with NPX in different conditions.
萘普生是一种非甾体抗炎药，在人类中表现出光毒性副作用，但光毒性的机制尚不清楚。为了揭示萘普生的光物理和光化学反应过程，我们采用飞秒到纳秒瞬态吸收光谱法直接检测了在纯乙腈、乙腈：水 1：1 和乙腈：PBS 1：1 溶液中萘普生在紫外光照射下的激发态和瞬态。瞬态吸收数据与基于时间依赖密度泛函理论分析预测的选定中间体的吸收光谱相结合，阐明了萘普生在不同溶液中的光化学反应机制。飞秒瞬态吸收结果表明，在各种溶液中最终产物形成之前的早期延迟时间内，萘普生有两种不同的光化学反应途径。在纯乙腈溶剂中，萘普生向溶剂发生电荷转移，生成自由基阳离子中间体，然后脱羧生成自由基 B 中间体。而在乙腈：PBS 1：1 溶液中，萘普生首先优先发生质子化，并被激发到单重激发态（NPX），然后发生系间窜跃，产生最低的三重态（T）。T 随后发生脱羧反应，生成自由基 B 物种。这些过程的动力学特征表明，乙腈：PBS 1：1 溶液中的脱羧反应比纯乙腈溶剂中的脱羧反应更快。对 NPX 的光物理和光化学过程的深入研究将有助于我们更好地理解在不同条件下与 NPX 相关的毒理学机制。
