Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Photochem Photobiol. 2021 Nov;97(6):1534-1547. doi: 10.1111/php.13480. Epub 2021 Jul 30.
8-Methoxypsoralen (8-MOP) serves as a PUVA (psoralen + UV-A) agent in the treatment of certain skin diseases. Derivatives of 8-MOP with cationic aromatic substituents at the five positions were synthesized and characterized by steady-state, femtosecond and nanosecond spectroscopy as well as cyclic voltammetry. The aromatic substituents' positive charge increases the water solubility and the affinity toward intercalation into DNA. The aromatic substituents were supposed to lower the psoralen S energy and thereby suppress a photo-induced electron transfer (PET) with guanine-bearing DNA. Such a suppression of this PET is expected to increase the propensity of psoralens to photo-addition to DNA. For derivatives bearing methylpyridinium residues, femtosecond spectroscopy revealed an intramolecular PET occurring on the picosecond time scale. This PET precludes the population of the triplet state. As triplet states are the precursor state for the photo-addition to DNA, their intermolecular PET renders these derivatives ineffective in terms of PUVA. For two derivatives bearing trimethylphenylammonium moieties, such an intramolecular PET does not occur and the triplet state is populated. Surprisingly, these compounds also exhibit no PUVA activity. Based on these findings, implications for further optimization of PUVA agents are discussed.
8-甲氧基补骨脂素（8-MOP）是一种用于治疗某些皮肤病的 PUVA（补骨脂素+长波紫外线 A）药物。在本研究中，合成了在 5 位带有正电荷芳香取代基的 8-MOP 衍生物，并通过稳态、飞秒和纳秒光谱以及循环伏安法对其进行了表征。芳香取代基的正电荷增加了水溶性和与 DNA 嵌入的亲和力。芳香取代基被认为可以降低补骨脂素 S 能，从而抑制与含鸟嘌呤的 DNA 的光诱导电子转移（PET）。这种 PET 的抑制作用预计会增加补骨脂素与 DNA 光加成的倾向。对于带有甲基吡啶鎓残基的衍生物，飞秒光谱显示出在皮秒时间尺度上发生的分子内 PET。这种 PET 阻止了三重态的产生。由于三重态是 DNA 光加成的前体状态，它们的分子间 PET 使得这些衍生物在 PUVA 方面无效。对于带有三甲基苯基铵部分的两个衍生物，这种分子内 PET 不会发生，并且三重态被占据。令人惊讶的是，这些化合物也没有表现出 PUVA 活性。基于这些发现，讨论了对进一步优化 PUVA 药物的影响。
