Umek Nejc
Institute of Anatomy, Faculty of Medicine, University of Ljubljana Korytkova ulica 2 1000 Ljubljana Slovenia
RSC Adv. 2020 Apr 28;10(28):16650-16658. doi: 10.1039/d0ra02713h. eCollection 2020 Apr 23.
Catecholamine autoxidation has been recognized as one of the potential trigger factors for catecholaminergic neuron loss characteristics of neurodegenerative diseases. The cyclization step with intramolecular Michael addition of catecholamine -quinones has been shown to be the irreversible and rate limiting step of the autoxidation reaction across a broad pH range and has a complex pH dependence that has not yet been fully understood. Using quantum chemical calculations, we demonstrated that in the case of noradrenaline and adrenaline two catecholamine -quinone species, one with an unprotonated and one with a protonated quinone group can participate in the cyclization reaction and that the mechanisms of these reactions significantly differ, emphasizing the importance of quinone group protonation states in the reaction mechanism. With a thorough exploration of the reaction kinetics, we further showed that at acidic pH the cyclization reaction rate is pH independent, while at alkaline pH the pH dependence is marked, explaining the experimentally observed complex pH dependence.
儿茶酚胺自氧化已被认为是神经退行性疾病中儿茶酚胺能神经元丢失特征的潜在触发因素之一。儿茶酚胺 - 醌的分子内迈克尔加成环化步骤已被证明是在广泛pH范围内自氧化反应的不可逆限速步骤，并且具有尚未完全理解的复杂pH依赖性。通过量子化学计算，我们证明，对于去甲肾上腺素和肾上腺素这两种儿茶酚胺 - 醌物种，一种具有未质子化醌基团，另一种具有质子化醌基团，均可参与环化反应，且这些反应的机制显著不同，强调了醌基团质子化状态在反应机制中的重要性。通过对反应动力学的深入研究，我们进一步表明，在酸性pH下，环化反应速率与pH无关，而在碱性pH下，pH依赖性显著，这解释了实验观察到的复杂pH依赖性。
