Musa Klefah A K, Eriksson Leif A
School of Science and Technology and Orebro Life Science Center Orebro University, 701 82, Orebro, Sweden.
Phys Chem Chem Phys. 2009 Jun 14;11(22):4601-10. doi: 10.1039/b900144a. Epub 2009 Mar 23.
Diclofenac (DF) is a widely used non-steroid anti-inflammatory drug, associated with a range of side effects. The phototoxicity of DF is studied herein employing computational quantum chemistry at the B3LYP/6-31G(d,p) level of theory. The results show that the drug readily absorbs radiation from the UV-region. The deprotonated form spontaneously dechlorinates from its triplet state leading to ring closure and formation of an active photoproduct: chlorocarbazole acetic acid, CCA. The formed CCA is also photodegraded easily from its deprotonated triplet state. Photodegradation routes of deprotonated CCA are decarboxylation (barrier less than 4.5 kcal mol(-1)) and dechlorination (barrier around 6.2 kcal mol(-1)). The energy barrier required for dechlorination to take place from the neutral from is about 20 kcal mol(-1). The differences between the molecular orbitals of the neutral and the deprotonated forms of DF and CCA and spectra obtained using time-dependent density-functional theory (TD-DFT), in addition to the different radical and oxygenated intermediate species formed during the photodegradation mechanism, are discussed in more detail. The theoretical results obtained herein are in line with the experimental results available to date.
双氯芬酸（DF）是一种广泛使用的非甾体抗炎药，伴有一系列副作用。本文采用B3LYP/6-31G(d,p)理论水平的计算量子化学方法研究了DF的光毒性。结果表明，该药物很容易吸收紫外区域的辐射。去质子化形式从其三重态自发脱氯，导致环化并形成活性光产物：氯咔唑乙酸（CCA）。形成的CCA也很容易从其去质子化三重态发生光降解。去质子化CCA的光降解途径是脱羧（势垒小于4.5 kcal mol⁻¹）和脱氯（势垒约为6.2 kcal mol⁻¹）。从中性形式进行脱氯所需的能垒约为20 kcal mol⁻¹。除了光降解机制中形成的不同自由基和含氧中间物种外，还更详细地讨论了DF和CCA的中性形式与去质子化形式的分子轨道之间的差异以及使用含时密度泛函理论（TD-DFT）获得的光谱。本文获得的理论结果与迄今为止的实验结果一致。
