Romero-Silva Antonio, Mora-Diez Nelaine, Alvarez-Idaboy J Raul
Facultad de Química, Universidad Nacional Autónoma de México, México DF 4510, Mexico.
Department of Chemistry, Thompson Rivers University, Kamloops, British Columbia V2C 0C8, Canada.
ACS Omega. 2018 Dec 4;3(12):16519-16528. doi: 10.1021/acsomega.8b02964. eCollection 2018 Dec 31.
Radicals in biochemical environments can lead to protein damage. Theoretical studies can help us to understand the observed radical selectivity. In this work, the kinetics and thermodynamics of the hydrogen-transfer (HT) and single-electron transfer (SET) reactions between a cysteine derivative and 17 free radicals of biological significance have been theoretically investigated in aqueous and lipid media. With the exception of the reaction with OCCl, all SET reactions in aqueous medium have rate constants in the diffusion-limited regime. The γ site of cysteine was found to be the most reactive for the HT reactions with all the radicals, with rate constants in the diffusion limit for OH, OCHCl, and OCCl. The HT reactions from the α and γ positions have very similar Δ° values and even though the β position is the least thermodynamically favored, when the HT from β is exergonic it is a more reactive site than α. The results obtained confirm that the Bell-Evans-Polanyi principle does not apply to the reactions between amino acid residues and free radicals and that reactivity comparisons demand proper kinetic calculations.
生物化学环境中的自由基会导致蛋白质损伤。理论研究有助于我们理解观察到的自由基选择性。在这项工作中，理论上研究了半胱氨酸衍生物与17种具有生物学意义的自由基在水性和脂质介质中的氢转移（HT）和单电子转移（SET）反应的动力学和热力学。除了与OCCl的反应外，水性介质中的所有SET反应的速率常数都处于扩散限制范围内。发现半胱氨酸的γ位点对于与所有自由基的HT反应最具反应性，对于OH、OCHCl和OCCl，其速率常数处于扩散极限。来自α和γ位置的HT反应具有非常相似的Δ°值，尽管β位置在热力学上最不利，但当来自β的HT是放能反应时，它是比α更具反应性的位点。获得的结果证实，贝尔-埃文斯-波拉尼原理不适用于氨基酸残基与自由基之间的反应，并且反应性比较需要适当的动力学计算。
