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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Density Functional Theory Study on the Demethylation Reaction between Methylamine, Dimethylamine, Trimethylamine, and Tamoxifen Catalyzed by a Fe(IV)–Oxo Porphyrin Complex
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Density Functional Theory Study on the Demethylation Reaction between Methylamine, Dimethylamine, Trimethylamine, and Tamoxifen Catalyzed by a Fe(IV)–Oxo Porphyrin Complex

机译：甲胺，二甲胺，三甲胺和Tamoxifen催化的甲胺，二甲胺与Fe（IV） - 过脱水卟啉复合物催化的密度泛函理论研究

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摘要

In this work, we studied computationally the N-demethylation reaction of methylamine, dimethylamine, and trimethylamine as archetypal examples of primary, secondary, and tertiary amines catalyzed by high-field low-spin Fe-containing enzymes such as cytochromes P450. Using DFT calculations, we found that the expected C–H hydroxylation process was achieved for trimethylamine. When dimethylamine and methylamine were studied, two different reaction mechanisms (C–H hydroxylation and a double hydrogen atom transfer) were computed to be energetically accessible and both are equally preferred. Both processes led to the formation of formaldehyde and the N-demethylated substrate. Finally, as an illustrative example, the relative contribution of the three primary oxidation routes of tamoxifen was rationalized through energetic barriers obtained from density functional calculations and docking experiments involving CYP3A4 and CYP2D6 isoforms. We found that the N-demethylation process was the intrinsically favored one, whereas other oxidation reactions required most likely preorganization imposed by the residues close to the active sites.
机译：在这项工作中，我们在计算上研究了甲胺，二甲胺和三甲胺的N-去甲基化反应作为由高领含量低纺丝酶如细胞变性P450催化的初级，仲和叔胺的初级，仲和胺的原型实例。使用DFT计算，我们发现对三甲胺实现了预期的C-H羟基化方法。当研究二甲胺和甲胺时，计算两种不同的反应机制（C-H羟基化和双氢原子转移）以便能量上可接近，两者同样优选。这两种过程都导致形成甲醛和N-脱甲基化底物。最后，作为说明性示例，三种初级氧化途径的三种初级氧化途径通过从密度函数计算和涉及CYP3A4和CYP2D6同种型的对接实验获得的能量屏障合理地合理化。我们发现N-去甲基化方法是本质上的优选，而其他氧化反应最可能被残留物均接近活性位点的残留物。

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    Nerea Alberro; Miquel Torrent-Sucarrat; Ana Arrieta; Gloria Rubiales; Fernando P. Cossío;

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    Department of Organic Chemistry I Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Centro de Innovación en Química Avanzada (ORFEO-CINQA) Manuel Lardizabal Ibilbidea 3 20018 San Sebastián/Donostia Spain;

    Department of Organic Chemistry I Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Centro de Innovación en Química Avanzada (ORFEO-CINQA) Manuel Lardizabal Ibilbidea 3 20018 San Sebastián/Donostia Spain;

    Department of Organic Chemistry I Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Centro de Innovación en Química Avanzada (ORFEO-CINQA) Manuel Lardizabal Ibilbidea 3 20018 San Sebastián/Donostia Spain;

    Department of Organic Chemistry I Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Centro de Innovación en Química Avanzada (ORFEO-CINQA) Manuel Lardizabal Ibilbidea 3 20018 San Sebastián/Donostia Spain;

    Department of Organic Chemistry I Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) Centro de Innovación en Química Avanzada (ORFEO-CINQA) Manuel Lardizabal Ibilbidea 3 20018 San Sebastián/Donostia Spain;

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  • 正文语种 eng
  • 中图分类 物理化学（理论化学）、化学物理学;
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