Department of Chemistry, The University of Hong Kong , Pokfulam Road, Pokfulam, Hong Kong S.A.R., P. R. China.
Department of Chemistry, Shantou University , Shantou 515063, China.
J Phys Chem B. 2017 Apr 6;121(13):2712-2720. doi: 10.1021/acs.jpcb.6b11934. Epub 2017 Mar 29.
Photoinduced dehalogenation of the antifungal drug itraconazole (ITR) in acetonitrile (ACN) and ACN/water mixed solutions was investigated using femtosecond and nanosecond time-resolved transient absorption (fs-TA and ns-TA, respectively) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR) experiments. An excited resonance energy transfer is found to take place from the 4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-one part of the molecule to the 1,3-dichlorobenzene part of the molecule when ITR is excited by ultraviolet light. This photoexcitation is followed by a fast carbon-halogen bond cleavage that leads to the generation of radical intermediates via either triplet and/or singlet excited states. It is found that the singlet excited state-mediated carbon-halogen cleavage is the predominant dehalogenation process in ACN solvent, whereas a triplet state-mediated carbon-halogen cleavage prefers to occur in the ACN/water mixed solutions. The singlet-to-triplet energy gap is decreased in the ACN/water mixed solvents and this helps facilitate an intersystem crossing process, and thus, the carbon-halogen bond cleavage happens mostly through an excited triplet state in the aqueous solutions examined. The ns-TA and ns-TR results also provide some evidence that radical intermediates are generated through a homolytic carbon-halogen bond cleavage via predominantly the singlet excited state pathway in ACN but via mainly the triplet state pathway in the aqueous solutions. In strong acidic solutions, protonation at the oxygen and/or nitrogen atoms of the 1,2,4-triazole-3-one group appears to hinder the dehalogenation reactions. This may offer the possibility that the phototoxicity of ITR due to the generation of aryl or halogen radicals can be reduced by protonation of certain moieties in suitably designed ITR halogen-containing derivatives.
采用飞秒和纳秒时间分辨瞬态吸收（fs-TA 和 ns-TA）和纳秒时间分辨共振拉曼光谱（ns-TR）实验研究了抗真菌药物伊曲康唑（ITR）在乙腈（ACN）和 ACN/水混合溶液中的光诱导脱卤反应。当 ITR 被紫外光激发时，发现分子的 4-苯基-4,5-二氢-3H-1,2,4-三唑-3-酮部分与分子的 1,3-二氯苯部分之间发生了激发共振能量转移。这种光激发随后导致碳-卤键快速断裂，通过三重态和/或单重态激发态生成自由基中间体。研究发现，在 ACN 溶剂中，单重态激发介导的碳-卤键断裂是主要的脱卤过程，而三重态介导的碳-卤键断裂更倾向于在 ACN/水混合溶液中发生。在 ACN/水混合溶剂中，单重态到三重态的能量间隙减小，这有助于促进系间窜越过程，因此，在所研究的水溶液中，碳-卤键断裂主要通过激发三重态发生。ns-TA 和 ns-TR 结果还提供了一些证据，表明自由基中间体是通过主要通过单重态激发途径通过均裂碳-卤键断裂产生的，而在水溶液中主要通过三重态途径产生的。在强酸性溶液中，1,2,4-三唑-3-酮基团的氧和/或氮原子的质子化似乎阻碍了脱卤反应。这可能提供了一种可能性，即通过某些部位的质子化，有可能降低由于生成芳基或卤基自由基而导致的 ITR 的光毒性，这些部位可以在适当设计的含有 ITR 卤化物的衍生物中。
