水液相下羟基自由基诱导半胱氨酸分子损伤的机理

Mechanism of Cysteine Molecular Damage Induced by Hydroxyl Radical in Water-Liquid Phase Environment

采用密度泛函理论的M06-2X和MN15方法,结合自洽反应场理论的SMD(solvation model based)模型方法,研究了水液相下羟基自由基(OH^(·))诱导半胱氨酸分子(Cys)损伤的反应机理。研究发现:Cys的损伤可通过OH^(·)抽取其H原子、OH^(·)加成到羧基C和单电子从Cys分子向OH^(·)转移3个通道实现。势能面计算表明:OH^(·)加成到羧基C的反应通道最具优势,是无势垒过程;OH^(·)抽取α-H、质子化氨基H、巯基H和亚甲基H的最低能垒分别是12.5、4.6、7.3、8.9 k J/mol;电子从Cys向OH^(·)转移的反应为劣势通道,能垒为93.5 k J/mol。结果表明,水液相下OH^(·)容易导致Cys分子损伤。

The reaction mechanism of cysteine molecular damage induced by hydroxyl radical in water-liquid phase environment was studied by means of M06-2X and MN15 methods based on density functional theory and SMD(solvation model based) model method of self consistent reaction field theory.The study shows that the damage of Cys can be achieved by three ways:OH^(·) extracting its H atom,OH^(·) adding to carboxyl C and single electron transferring to OH^(·) from Cys molecule,all of which could induce Cys damage.Investigation on the potential energy surface shows that the reaction of OH^(·) adding to carboxyl C has the most advantage,and the process is barrierfree;the lowest barriers for OH^(·) radicals extracting α-H and protonating amino group H,mercapto group H and methylene H are 12.5,4.6,7.3 and 8.9 k J/mol,respectively.The reaction of electron transferring to OH^(·) from Cys molecule is a disadvantage channel with the barrier as 93.5 k J/mol.The results show that OH^(·) can cause Cys molecular damage easily in water-liquid phase environment.