Abstract

Pterins are naturally occurring pigments and enzyme cofactors widespread in living organisms. Tetrahydrobiopterin (H₄Bip) is a coenzyme of aromatic amino acid hydroxylases, NO-synthases, and alkylglycerol monooxygenases. This coenzyme is prone to oxidation in the presence of molecular oxygen, a so-called autoxidation. The reactions participating in H₄Bip autoxidation are well known. However, our study is an attempt to evaluate theoretically the feasibility of reactions participating in autoxidation. To do so, we have calculated the Gibbs free energy of elementary reactions between H₄Bip, its derivatives, molecular oxygen, and reactive oxygen species (ROS). In the last few years, we have established the photosensitized oxidation of H₄Bip experimentally. Thus, we have also evaluated the feasibility of H₄Bip photooxidation reactions, which may occur according to both type-I and type-II photosensitized oxidation. We calculated Fukui indices for H₄Bip and found particular atoms in the molecule that interact with nucleophiles (for example, singlet oxygen ¹O₂) and radicals (in particular, molecular oxygen ³O₂). Therefore, we evaluated the probability of H₄Bip autoxidation reactions, photooxidation reactions, and the reactivity of particular atoms in H₄Bip molecule using the theoretical methods of quantum chemistry.

摘要

蝶呤是在生物体中广泛存在的天然色素和酶辅因子。四氢生物蝶呤（H ₄ Bip）是芳香族氨基酸羟化酶，一氧化氮合酶和烷基甘油单加氧酶的辅酶。这种辅酶在分子氧存在下易于氧化，即所谓的自氧化。参与H ₄ Bip自氧化的反应是众所周知的。但是，我们的研究是从理论上评估参与自氧化反应的可行性的尝试。为此，我们计算了H ₄ Bip，其衍生物，分子氧和活性氧（ROS）之间基本反应的吉布斯自由能。在过去的几年中，我们已经建立了H ₄的光敏氧化以实验方式进行Bip。因此，我们还评估了根据I型和II型光敏氧化可能发生的H ₄ Bip光氧化反应的可行性。我们计算了H ₄ Bip的Fukui指数，并发现了分子中与亲核试剂（例如单线态氧¹ O ₂）和自由基（特别是分子氧³ O ₂）相互作用的特定原子。因此，我们使用量子化学的理论方法评估了H ₄ Bip自氧化反应，光氧化反应的可能性以及H ₄ Bip分子中特定原子的反应性。