Jordaan Maryam A, Shapi Michael
Department of Chemistry, Faculty of Natural Sciences, 70688 Mangosuthu University of Technology , Durban, South Africa.
Antivir Chem Chemother. 2017 Dec;25(3):94-104. doi: 10.1177/2040206617730170. Epub 2017 Sep 11.
This study sought to investigate the solvent-dependency on the photolysis of efavirenz to gain insight into the photoprocesses involved. The primary mechanisms were firstly the excited-state intramolecular proton transfer (i.e. phototautomerization), which generated the imidic acid phototautomer observed as [M-H] quasimolecular ion at m/z 314.0070 in the high-performance liquid chromatography-electrospray ionization-time-of-flight mass spectrometry in the negative mode. Secondly, the photoinduced α-cleavage with the loss of a carbonyl group occurred (i.e. photodecarbonylation) to form the photoproduct at m/z 286.0395. The ultraviolet-visible spectra illustrated a large, hyperchromic, and slight bathochromic effect in both the π→π* and n→π* electronic transitions. The largest bathochromic effect was prevalent in the chloroform solvent, i.e. chloroform (π* = 0.58; β = 0.00; α = 0.44) > methanol (π* = 0.60; β = 0.66; α = 0.98) > acetonitrile (π* = 0.75; β = 0.40; α = 0.19). This is due to the significant interaction of the amino group with the excited carbonyl moiety which is attributed to intramolecular phototautomerization resulting in a larger energy shift of the electronic state. A plausible explanation is due to the hydrogen bond donor ability of the polar methanol and nonpolar chloroform solvents, which stabilized the polarized imidic acid phototautomer by means of hydrogen bonding interactions, as opposed to the aprotic acetonitrile which exhibits no hydrogen bonding interactions. The study would form the basis for further photolytic analyses and syntheses to generate a plethora of novel photoproducts with anti-HIV activity based on the biologically active benzoxazinone framework of efavirenz.
本研究旨在探究溶剂对依非韦伦光解的依赖性，以深入了解其中涉及的光化学过程。主要机制首先是激发态分子内质子转移（即光互变异构），在高效液相色谱 - 电喷雾电离 - 飞行时间质谱的负模式下，产生了在m/z 314.0070处观察到的亚氨酸光互变异构体，表现为[M - H]准分子离子。其次，发生了伴随羰基损失的光诱导α - 裂解（即光脱羰作用），形成了m/z 286.0395处的光产物。紫外 - 可见光谱表明，在π→π和n→π电子跃迁中均出现了大的、增色的且轻微的红移效应。最大的红移效应在氯仿溶剂中最为显著，即氯仿（π* = 0.58；β = 0.00；α = 0.44）＞甲醇（π* = 0.60；β = 0.66；α = 0.98）＞乙腈（π* = 0.75；β = 0.40；α = 0.19）。这是由于氨基与激发态羰基部分之间的显著相互作用，这归因于分子内光互变异构导致电子态的更大能量位移。一个合理的解释是，极性甲醇和非极性氯仿溶剂的氢键供体能力通过氢键相互作用稳定了极化的亚氨酸光互变异构体，与之形成对比的是，非质子乙腈不存在氢键相互作用。该研究将为进一步的光解分析和合成奠定基础，以基于依非韦伦的生物活性苯并恶嗪酮骨架生成大量具有抗HIV活性的新型光产物。
