在使用 DFT 和 UPLC-Q-TOF MS/MS 方法的基基-甲基马反应中识别过渡物和转化产物
Kavanal P Prasanthkumar1, Faseelath Valayankadan1, Charuvila T Aravindakumar2,3
1Post Graduate and Research Department of Chemistry, Maharaja's College, Ernakulam 682 011, India.
The journal of physical chemistry. B
|February 6, 2024
概括
研究了抗甲状腺药物甲基马 (MMI) 与基基 (·OH) 的氧化反应. 单个电子转移是主要的途径,在模拟生理条件下导致转化产物的形成.
科学领域:
- 环境化学环境化学
- 药用化学 医学化学
- 计算化学计算化学
背景情况:
- 了解药品的氧化降解对于评估它们的环境命运和生物活性至关重要.
- 甲基 (MMI) 是一种广泛使用的抗甲状腺药物,其与基基 (·OH) 等活性氧物种的反应尚未完全理解.
研究的目的:
- 阐明反应机制,并确定甲基马 (MMI) 被基基 (·OH) 氧化后的转化产物 (TP).
- 确定主导氧化途径并评估MMI在生理学上相关条件下对自由基物种的敏感性.
主要方法:
- 密度函数理论 (DFT) 计算的协同应用 (M06-2X/6-311++G(d,p) /SMD(水)) 和超高性能液态染色学-四极点飞行时间并列质谱学 (UPLC-Q-TOF MS/MS).
- 计算探测原子抽象 (HA),激素添加物形成 (RAF) 和单个电子转移 (SET) 反应通道.
- 通过H2O2的紫外线光解产生OH基来与MMI反应,然后通过UPLC-Q-TOFMS/MS分析进行TP识别.
主要成果:
- 对于大多数OH-MMI反应,DFT计算预测了无障碍路径,其中SET被确定为主要的氧化路径 (44%的分支比率).
- 实验分析确定了MMI的十个转化产物 (TP),它们的结构通过碎片化模式得到证实.
- 类型的甲基素 (MSeI) 显示了与MMI相似的反应模式,表明对OH氧化具有相似的敏感性.
结论:
- 单电子转移是由基基 (·OH) 氧化甲基马 (MMI) 的主要机制.
- 该研究成功地确定了MMI的关键转化产品,提供了对其降解途径的见解.
- 甲基对自由基物种表现出显著的敏感性,这对于理解其在生物和环境系统中的行为很重要.
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