Carreon-Gonzalez Mirzam, Muñoz-Rugeles Leonardo, Vivier-Bunge Annik, Alvarez-Idaboy Juan Raul
Facultad de Química, Departamento de Física y Química Teórica, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Laboratorio de Espectroscopia Atómica y Molecular (LEAM), Universidad Industrial de Santander, Bucaramanga, Colombia.
J Comput Chem. 2022 Mar 30;43(8):556-567. doi: 10.1002/jcc.26813. Epub 2022 Feb 1.
Thiophenols are chemical species with multiple desirable biological properties, including their primary and secondary antioxidant capacity. In this work, the repairing antioxidant activity of eight different thiophenols has been investigated for damaged leucine and tryptophane. The investigation was carried out employing quantum mechanical and transition state methods to calculate the thermodynamic and kinetic data of the reactions involved, while simulating the biological conditions at physiological pH and aqueous and lipidic medium. The analysis of the atomic charges and the spin densities at each of the points on the potential energy surface was the tool that allowed the elucidation of the reaction mechanisms through which thiophenols repair the oxidative damage caused to the amino acids leucine and tryptophan. It was found that thiophenols can repair leucine via a hydrogen atom transfer mechanism in a manner which is similar to the one used by glutathione to repair the carbon-centered radicals of guanosine. In addition, thiophenols can also restore tryptophane, a nitrogen-centered radical, via proton-coupled electron transfer and single electron transfer mechanisms. Moreover, both processes occur at close to diffusion-controlled rates.
苯硫酚是具有多种理想生物学特性的化学物质，包括其一级和二级抗氧化能力。在这项工作中，研究了八种不同苯硫酚对受损亮氨酸和色氨酸的修复抗氧化活性。研究采用量子力学和过渡态方法进行，以计算所涉及反应的热力学和动力学数据，同时模拟生理pH值以及水性和脂质介质中的生物学条件。对势能面上各点的原子电荷和自旋密度进行分析，这一工具使得阐明苯硫酚修复亮氨酸和色氨酸氧化损伤的反应机制成为可能。结果发现，苯硫酚可以通过氢原子转移机制修复亮氨酸，其方式类似于谷胱甘肽修复鸟苷碳中心自由基的方式。此外，苯硫酚还可以通过质子耦合电子转移和单电子转移机制恢复色氨酸（一种氮中心自由基）。而且，这两个过程都以接近扩散控制的速率发生。
