Kang Young Kee, Byun Byung Jin
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
J Phys Chem B. 2007 May 17;111(19):5377-85. doi: 10.1021/jp067826t. Epub 2007 Apr 18.
The conformational study of N-acetyl-N'-methylamide of azaproline (Ac-azPro-NHMe, the azPro dipeptide) is carried out using ab initio HF and density functional methods with the self-consistent reaction field method to explore the effects of the replacement of the backbone CHalpha group by the nitrogen atom on the conformational preferences and prolyl cis-trans isomerization in the gas phase and in solution (chloroform and water). The incorporation of the Nalpha atom into the prolyl ring results in the different puckering, backbone population, and barriers to prolyl cis-trans isomerization from those of Ac-Pro-NHMe (the Pro dipeptide). In particular, the azPro dipeptide has a dominant backbone conformation D (beta2) with the cis peptide bond preceding the azPro residue in both the gas phase and solution. This may be ascribed to the favorable electrostatic interaction or intramolecular hydrogen bond between the prolyl nitrogen and the amide hydrogen following the azPro residue and to the absence of the unfavorable interactions between electron lone pairs of the acetyl carbonyl oxygen and the prolyl Nalpha. This calculated higher population of the cis peptide bond is consistent with the results from X-ray and NMR experiments. As the solvent polarity increases, the conformations B and B* with the trans peptide bond become more populated and the cis population decreases more, which is opposite to the results for the Pro dipeptide. The conformation B lies between conformations D and A (alpha) and conformation B* is a mirror image of the conformation B on the phi-psi map. The barriers to prolyl cis-trans isomerization for the azPro dipeptide increase with the increase of solvent polarity, and the cis-trans isomerization proceeds through only the clockwise rotation with omega' approximately +120 degrees about the prolyl peptide bond for the azPro dipeptide in the gas phase and in solution, as seen for the Pro dipeptide. The pertinent distance d(N...H-NNHMe) and the pyramidality of imide nitrogen can describe the role of this hydrogen bond in stabilizing the transition state structure and the lower rotational barriers for the azPro dipeptide than those for the Pro dipeptide in the gas phase and in solution.
利用从头算HF和密度泛函方法以及自洽反应场方法，对氮杂脯氨酸的N - 乙酰基 - N'- 甲基酰胺（Ac - azPro - NHMe，氮杂脯氨酸二肽）进行构象研究，以探究在气相和溶液（氯仿和水）中，脯氨酸主链上的CHα基团被氮原子取代后对构象偏好和脯氨酰顺反异构化的影响。将Nα原子引入脯氨酰环导致其褶皱、主链构象分布以及脯氨酰顺反异构化的势垒与Ac - Pro - NHMe（脯氨酸二肽）不同。特别地，氮杂脯氨酸二肽在气相和溶液中都具有占主导地位的主链构象D（β2），且在氮杂脯氨酸残基之前的肽键为顺式。这可能归因于脯氨酰氮与氮杂脯氨酸残基之后的酰胺氢之间有利的静电相互作用或分子内氢键，以及乙酰羰基氧的孤对电子与脯氨酰Nα之间不存在不利相互作用。计算得出的较高的顺式肽键构象分布与X射线和核磁共振实验结果一致。随着溶剂极性增加，具有反式肽键的构象B和B的比例增加，顺式比例减少得更多，这与脯氨酸二肽的结果相反。构象B位于构象D和A（α）之间，构象B在φ - ψ图上是构象B的镜像。氮杂脯氨酸二肽的脯氨酰顺反异构化势垒随着溶剂极性的增加而升高，并且在气相和溶液中，氮杂脯氨酸二肽的顺反异构化仅通过围绕脯氨酰肽键以大约 +120°的ω'进行顺时针旋转，这与脯氨酸二肽的情况相同。相关距离d(N...H - NNHMe)和酰亚胺氮的锥角可以描述该氢键在稳定过渡态结构中的作用，以及在气相和溶液中氮杂脯氨酸二肽比脯氨酸二肽具有更低的旋转势垒。
