The hydroxyl radical (•OH) scavenging activities of Melatonin, an endogenously produced neurohormone and its related indolamines like N-acetyl tryptophan (NAT) and N-acetyl serotonin (NAS) have been investigated using density functional theory. The mechanism involves 4 steps: initial radical addition to position-3 of the indole ring, keto-amine to enol-imine tautomerization, cyclisation, and finally, addition of a second •OH leading to a cyclic end product. Incorporation of an explicit water molecule in tautomerization step leads to a significant reduction in the barrier of this step, so that the subsequent cyclisation step becomes rate-limiting. In agreement with the very high reactivity of •OH, the initial and final addition of •OH to indolamine are found to be barrierless. Radical adduct formed in the initial step was found to be very stable due to the extensive conjugation present in the substrate. Our calculations show that melatonin is the most effective radical scavenger among the three molecules chosen. NAS was found to exhibit antiradical property comparable to that of melatonin. In contrast to the general observation of reduced antioxidant activity of tryptophan, a non-natural derivative of tryptophan used here (NAT) is found to have good radical scavenging activity. This work further implies that non-natural derivatives of indolamines might as well be useful in the detoxification of free radicals as they exhibit almost comparable antioxidant efficiency as that of melatonin.

褪黑激素（一种内源性产生的神经激素）及其相关的吲哚胺（如N-乙酰色氨酸（NAT）和N）的羟自由基（•OH）清除活性-乙酰5-羟色胺（NAS）已使用密度泛函理论进行了研究。该机理涉及4个步骤：初始自由基加成至吲哚环的3位，将酮胺加至烯醇-亚胺互变异构体，环化，最后加成第二个•OH，生成环状最终产物。在互变异构化步骤中掺入明确的水分子导致该步骤的屏障的显着降低，使得随后的环化步骤成为速率限制。与•OH的极高反应性相一致，发现将•OH最初和最终添加到吲哚胺中是无障碍的。发现在初始步骤中形成的自由基加合物由于在基质中存在广泛的共轭而非常稳定。我们的计算表明，褪黑激素是所选三种分子中最有效的自由基清除剂。发现NAS显示出与褪黑激素相当的抗自由基性质。与色氨酸的抗氧化活性降低的一般观察结果相反，发现此处使用的色氨酸的非天然衍生物（NAT）具有良好的自由基清除活性。这项工作进一步暗示，吲哚胺的非天然衍生物也可能在自由基排毒中有用，因为它们显示出与褪黑激素几乎相同的抗氧化效率。发现此处使用的色氨酸的非天然衍生物（NAT）具有良好的自由基清除活性。这项工作进一步暗示，吲哚胺的非天然衍生物也可能在自由基排毒中有用，因为它们显示出与褪黑激素几乎相同的抗氧化效率。发现此处使用的色氨酸的非天然衍生物（NAT）具有良好的自由基清除活性。这项工作进一步暗示，吲哚胺的非天然衍生物也可能在自由基排毒中有用，因为它们显示出与褪黑素几乎相同的抗氧化效率。