Musa Klefah A K, Eriksson Leif A
Department of Natural Sciences and Orebro Life Science Center, Orebro University, 701 82 Orebro, Sweden.
J Phys Chem A. 2008 Oct 30;112(43):10921-30. doi: 10.1021/jp805614y. Epub 2008 Oct 4.
Density functional theory using the hybrid functional B3LYP has been employed in order to study the mechanisms of photoinduced decomposition of the closely related nonsteroidal anti-inflammatory drugs naproxen (NP) and 6-methoxy-2-naphthylacetic acid (MNAA; the active form of nabumetone). The photochemical properties and computed energies of various species obtained in this study show that both drugs dominate in their deprotonated forms at physiological pH. The deprotonated acids are unable to decarboxylate from their excited singlets; instead, they decarboxylate from their first excited triplet states with high efficiency, overcoming energy barriers less than 3 and 1 kcal/mol for MNAA and NP, respectively. The ultraviolet and visible spectra of the neutral, deprotonated, and decarboxylated moieties of MNAA and NP are more-or-less similar but with higher probabilites (oscillator strength) for the latter. This fact, as well as the higher reactivity of NP, is explained in terms of the electron-donating effect of the additional methyl group present in NP. Singlet oxygen, superoxide radical anion, and corresponding peroxyl radical species are expected to be formed in different steps throughout the proposed photodegradation pathways of both drugs, which give rise to their effects on biomolecules, for example, lipid peroxidation.
为了研究密切相关的非甾体抗炎药萘普生（NP）和6-甲氧基-2-萘乙酸（MNAA；萘丁美酮的活性形式）的光致分解机制，采用了使用杂化泛函B3LYP的密度泛函理论。本研究中获得的各种物种的光化学性质和计算能量表明，这两种药物在生理pH值下均以去质子化形式占主导。去质子化的酸不能从其激发单重态脱羧；相反，它们从第一激发三重态高效脱羧，MNAA和NP克服的能垒分别小于3千卡/摩尔和1千卡/摩尔。MNAA和NP的中性、去质子化和脱羧部分的紫外和可见光谱或多或少相似，但后者具有更高的概率（振子强度）。这一事实以及NP的更高反应活性，是根据NP中存在的额外甲基的给电子效应来解释的。预计在这两种药物提出的光降解途径的不同步骤中会形成单线态氧、超氧自由基阴离子和相应的过氧自由基物种，这导致它们对生物分子产生影响，例如脂质过氧化。
