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硫胺素去质子化机制。噻唑鎓和嘧啶基亚胺的最低未占分子轨道协同作用使碳负离子得以稳定形成,且释放过程受氢键开关控制。

Thiamin deprotonation mechanism. Carbanion development stabilized by the LUMOs of thiazolium and pyrimidylimine working in tandem and release governed by a H-bond switch.

作者信息

DuPré Donald B, Wong John L

机构信息

Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA.

出版信息

J Phys Chem A. 2007 Mar 22;111(11):2172-81. doi: 10.1021/jp067308i. Epub 2007 Feb 23.

Abstract

Our previous paper (J. Phys. Chem. A 2005, 109, 7606) using computed atomic charges, based on the quantum theory of atoms in molecules (QTAIM), on azolium models of thiamin diphosphate has shown that only sulfur acts as an effective electron sink in the formation of the thiamin carbanion intermediate. Herein we apply natural bond orbital (NBO) theory to the analysis of orbital contributions to canonical molecular orbitals (CMOs) of six abbreviated azolium analogs of the carbanion to better understand the unique function of sulfur. The NBO/CMO data provide a description of the origin of the first thiamin electron sink: sulfur performing in the sigma- and pi-orbitals of the transition state as well as in the carbanion, and its advantages due to low electronegativity and moderate size. At the next level of thiamin modeling, we include the six-membered pyrimidine ring to represent the prerequisite V-structure in the iminopyrimidine tautomeric form. This model is subjected to incremental deprotonation and MO decomposition. The 4'-pyrimidylimine moiety, in addition to being an internal base to abstract the C2 proton, also performs as the second electron sink. Thus, the LUMOs of the thiazolium and pyrimidylimine systems working in tandem stabilize the developing charges in these transient structures, with facilitation from their HOMOs. Further, the absence of detectable amounts of the C2 carbanion in 13C2-labeled thiamin-enzyme complex by NMR is explained. Both NBO analysis and the QTAIM topological electronic properties suggest the operation of a H-bonding scheme that leads to the formation of a cryptic C2 carbanion that is not accumulated. The shielding of the carbanion by the N4'-H hydrogen bond is weakened by N1'-H deprotonation. Consequently, prior return of the N1' proton to the nearby glutamate may be the switch for streaming a timed-release of the unstable C2 carbanion to the incoming substrate.

摘要

我们之前的论文(《物理化学杂志A》2005年,第109卷,第7606页)基于分子中原子的量子理论(QTAIM),使用计算得到的原子电荷对硫胺二磷酸的唑鎓模型进行研究,结果表明在硫胺碳负离子中间体的形成过程中,只有硫作为有效的电子受体。在此,我们应用自然键轨道(NBO)理论来分析六个碳负离子的简化唑鎓类似物对正则分子轨道(CMO)的轨道贡献,以便更好地理解硫的独特功能。NBO/CMO数据描述了硫胺第一个电子受体的起源:硫在过渡态以及碳负离子的σ轨道和π轨道中发挥作用,并且由于其低电负性和适中的尺寸而具有优势。在硫胺建模的下一个层次,我们纳入六元嘧啶环以代表亚氨基嘧啶互变异构形式中的必备V结构。对该模型进行逐步去质子化和分子轨道分解。4'-嘧啶基亚胺部分除了作为夺取C2质子的内部碱之外,还充当第二个电子受体。因此,噻唑鎓和嘧啶基亚胺系统的最低未占分子轨道协同作用,在其最高已占分子轨道的促进下,稳定了这些瞬态结构中正在形成的电荷。此外,还解释了通过核磁共振在13C2标记的硫胺 - 酶复合物中未检测到可检测量的C2碳负离子的原因。NBO分析和QTAIM拓扑电子性质均表明存在一种氢键作用机制,该机制导致形成一种未积累的隐蔽C2碳负离子。N4'-H氢键对碳负离子的屏蔽作用因N1'-H去质子化而减弱。因此,N1'质子提前返回附近的谷氨酸可能是将不稳定的C2碳负离子定时释放到进入的底物中的开关。

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