CONACYT - Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C. P. 09340, México D. F., Mexico.
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, Iztapalapa C. P. 09340, México D. F., Mexico.
Biochim Biophys Acta Gen Subj. 2017 Sep;1861(9):2206-2217. doi: 10.1016/j.bbagen.2017.06.016. Epub 2017 Jun 24.
Melatonin is well known for its antioxidant capacity, which has been attributed to the combined protective effects of the parent molecule and its metabolites. However, the potential role of 2-hydroxymelatonin (2OHM) and 4-hydroxymelatonin (4OHM) in such protection has not been previously investigated.
The calculations were performed using the Density Functional Theory, with the M05-2X and M05 functionals, the 6-311+G(d,p) basis set and the solvation model based on density (SMD).
4OHM shows excellent antioxidant activity via radical-trapping, reacting with peroxyl radicals faster than Trolox and melatonin. 4OHM can be moderately efficient as a preventing antioxidant by inhibiting Cu(II). This effect would lower the Cu(I) availability, which is the redox state required for the OH to be formed, via Fenton-like reactions. 4OHM turns off the oxidant effects of copper-ascorbate mixtures. The presence of a phenolic group was identified as the key structural feature in the antioxidant activity of 4OHM. On the other hand, 2OHM does not present a phenolic group, despite its formal name. Its keto tautomer was identified as the most abundant one (~100%). This may explain the relative low antioxidant protection of 2OHM.
4OHM significantly contributes to the overall antioxidant activity exhibited by melatonin, while the effects of 2OHM in this context are predicted to be only minor. This low reactivity might justify the relatively large abundance of 2OHM in biological systems.
Hydroxylated melatonin metabolites, such as 4OHM, may play an important role in the protective effects of melatonin against oxidative stress.
褪黑素以其抗氧化能力而闻名，这种能力归因于母体分子及其代谢物的综合保护作用。然而，2-羟褪黑素（2OHM）和 4-羟褪黑素（4OHM）在这种保护中的潜在作用尚未被研究过。
使用密度泛函理论进行计算，采用 M05-2X 和 M05 泛函、6-311+G（d，p）基组和基于密度的溶剂化模型（SMD）。
4OHM 通过自由基捕获显示出优异的抗氧化活性，与过氧自由基的反应速度比 Trolox 和褪黑素更快。4OHM 可以通过抑制 Cu(II)作为一种中等有效的预防抗氧化剂。这种效应会降低 Cu(I)的可用性，这是通过芬顿样反应形成 OH 所必需的氧化还原状态。4OHM 可以关闭铜-抗坏血酸混合物的氧化剂效应。酚基团的存在被确定为 4OHM 抗氧化活性的关键结构特征。另一方面，2OHM 尽管有其正式名称，但没有酚基团。它的酮式互变异构体被确定为最丰富的一种（~100%）。这可以解释 2OHM 相对较低的抗氧化保护作用。
4OHM 显著促进了褪黑素所表现出的整体抗氧化活性，而 2OHM 在这种情况下的作用预计是次要的。这种低反应性可能解释了生物系统中 2OHM 相对大量存在的原因。
羟化褪黑素代谢物，如 4OHM，可能在褪黑素对抗氧化应激的保护作用中发挥重要作用。
