Flores-Ortega Alejandra, Casanovas Jordi, Assfeld Xavier, Alemán Carlos
Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Avda. Diagonal no. 647, 08028 Barcelona, Spain.
J Org Chem. 2009 Apr 17;74(8):3101-8. doi: 10.1021/jo900169s.
This work shows the influence of the side-chain protonation on the conformational properties, relative stabilities, and peptide bond isomerization of four aminoproline isomers. Thus, this research has been useful to define the rules that allow control the conformation of aminoproline with the pH. Comparison of the results obtained using density functional theory calculations for the N-acetyl-N'-methylamide derivatives of the protonated isomers, which differ in the beta- or gamma-position of the substituent and its cis or trans relative disposition, with those reported for the corresponding neutral analogues (J. Phys. Chem. B 2008, 112, 14045) has allowed us to reach the following conclusions: (i) protonation of the amino group produces a reduction of the backbone conformational flexibility and a destabilization of the cis configuration of the amide bond involving the pyrrolidine nitrogen; (ii) the planarity of the peptide bond is broken in some cases to form strong side chain...backbone interactions, which induce a very significant pyramidilization at the amide nitrogen atom; (iii) as was also detected for the neutral analogues, the formation of side chain...backbone intraresidue interactions favor the cis disposition of the substituent; and (iv) protonation of the amino side group increases the energy gaps that separate the different investigated isomers resulting in an enhancement of the destabilization of the dipeptides with the substituent attached in a trans position.
这项工作展示了侧链质子化对四种氨基脯氨酸异构体的构象性质、相对稳定性和肽键异构化的影响。因此，本研究对于确定能够通过pH值控制氨基脯氨酸构象的规则很有帮助。将质子化异构体（其取代基在β或γ位以及其顺式或反式相对构型不同）的N - 乙酰 - N'- 甲基酰胺衍生物使用密度泛函理论计算得到的结果与相应中性类似物（《物理化学杂志B》2008年，第112卷，第14045页）所报道的结果进行比较，使我们得出以下结论：（i）氨基的质子化导致主链构象灵活性降低以及涉及吡咯烷氮的酰胺键顺式构型不稳定；（ii）在某些情况下肽键的平面性被打破以形成强的侧链……主链相互作用，这在酰胺氮原子处诱导出非常显著的锥化；（iii）正如在中性类似物中也检测到的那样，侧链……主链残基内相互作用的形成有利于取代基的顺式构型；以及（iv）氨基侧基的质子化增加了分隔不同研究异构体的能隙，导致带有反式连接取代基的二肽的不稳定增强。
