Comparison between electrochemistry/mass spectrometry and cytochrome P450 catalyzed oxidation reactions
Comparison between electrochemistry/mass spectrometry and cytochrome P450 catalyzed oxidation reactions
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DOI：
10.1002/rcm.978
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发表时间：
2003-01-01
影响因子：
2
通讯作者：
Bruins, AP
中科院分区：
文献类型：
--
作者：
Jurva, U;Wikström, HV;Bruins, AP
在线电化学与电喷雾质谱法可在多大程度上用于模拟细胞色素 P450 催化的氧化反应。我们对大多数反应进行了机械层面的比较，以解释为什么某些反应可以（而有些反应不能）通过电化学氧化来模拟。 EC/MS/MS 系统成功地模拟了 P450 催化反应通过单电子氧化引发的机制进行的情况，例如 N-脱烷基化、S-氧化、P-氧化、醇氧化和脱氢。通过直接夺取氢原子引发的P450催化反应，例如O-脱烷基化和未取代芳环的羟基化，通常具有太高的氧化电位，无法在水的氧化电位极限以下进行电化学氧化，并且不能被EC/MS/MS系统模拟。尽管 EC/MS/MS 系统无法模拟细胞色素 P450 进行的所有氧化，但可以获得有关底物对氧化的敏感性以及分子氧化可能发生在哪个位置的有价值的信息。对于从药物开始的代谢物的小规模电化学合成，EC/MS/MS 系统对于快速优化电化学条件应该非常有用。该系统的简单性以及可轻松快速地应用于大量化合物，使其成为药物代谢研究中的有用工具。版权所有 (C) 2003 John Wiley Sons, Ltd.
The extent to which electrochemistry on-line with electrospray mass spectrometry can be used to mimic cytochrome P450 catalyzed oxidations has been investigated. Comparisons on the mechanistic level have been made for most reactions in an effort to explain why certain reactions can, and some cannot, be mimicked by electrochemical oxidations. The EC/MS/MS system used successfully mimics in cases where the P450 catalyzed reactions are supposed to proceed via a mechanism initiated by a one-electron oxidation, such as N-dealkylation, S-oxidation, P-oxidation, alcohol oxidation and dehydrogenation. The P450 catalyzed reactions initiated via direct hydrogen atom abstraction, such as O-dealkylation and hydroxylation of unsubstituted aromatic rings, generally had a too high oxidation potential to be electrochemically oxidized below the oxidation potential limit of water, and were not mimicked by the EC/MS/MS system. Even though the EC/MS/MS system is not able to mimic all oxidations performed by cytochrome P450, valuable information can be obtained concerning the sensitivity of the substrate towards oxidation and in which position of the molecule oxidations are likely to take place. For small-scale electrochemical synthesis of metabolites, starting from the drug, the EC/MS/MS system should be very useful for quick optimization of the electrochemical conditions. The simplicity of the system, and the ease and speed with which it can be applied to a large number of compounds, make it a useful tool in drug metabolism research. Copyright (C) 2003 John Wiley Sons, Ltd.