Quantum Mechanical and NMR Studies of Ring Puckering and cis/trans-Rotameric Interconversion in Prolines and Hydroxyprolines
Quantum Mechanical and NMR Studies of Ring Puckering and cis/trans-Rotameric Interconversion in Prolines and Hydroxyprolines
复制标题
DOI：
10.1021/jp906006w
复制
发表时间：
2009-10-08
影响因子：
2.9
通讯作者：
Courtier-Murias, Denis
中科院分区：
文献类型：
--
作者：
Aliev, Abil E.;Bhandal, Simrath;Courtier-Murias, Denis
脯氨酸（Pro）含有n -乙酰基- l-脯氨酸（AcProOH）和n -乙酰基-4-羟基- l-脯氨酸（AcHypOH）。本文还报道了Gly-Pro-Gly-Gly （GPGG）、Val-Ala-Pro-Gly （VAPG）和Ala-Pro-Gly-Trp酰胺醋酸盐（APGW）变温核磁共振测量的初步结果。通过温度相关核磁共振研究了溶剂（D2O, DMSO-d(6)和CD3CN）对吡咯烷环构象和顺/反式旋转聚合的影响，然后使用QM方法对两种构象平衡进行了详细的过渡态（TS）搜索。结果揭示了TS的能量特征，与核磁共振相吻合，并得到了相应的TS几何形状，这是实验所不能得到的。顺/反式旋转聚合最显著的特征是AcProOH和AcHypOH中的酰胺态氮在TS中采用四面体几何结构，采用各种HF、DFT和MP2计算以及隐式溶剂化模型来确定最合适的QM方案，以可靠地预测水溶液中含有Pro和Hyp的肽的几何形状和相对能量。溶液核磁共振结果用于验证QM预测的可靠性。结果表明，MP2计算结合隐式溶剂化模型在重现不同溶剂中AcProOH或AcHypOH的四种不同构象的核磁共振测量种群时是相当准确的，而HF和DFT B3LYP计算的准确性明显较低。
Nuclear magnetic resonance (NMR) and quantum mechanical (QM) studies have been carried out for proline (Pro) containing peptides: N-acetyl-L-proline (AcProOH) and N-acetyl-4-hydroxy-L-proline (AcHypOH). Preliminary results of variable temperature NMR measurements for Gly-Pro-Gly-Gly (GPGG), Val-Ala-Pro-Gly (VAPG), and Ala-Pro-Gly-Trp amide acetate salt (APGW) are also reported. The effect of solvent (D2O, DMSO-d(6) and CD3CN) on the pyrrolidine ring conformation and cis/trans-rotamerisation along the amide bond preceding Pro was investigated by temperature dependent NMR followed by detailed transition state (TS) searches for both conformational equilibria using QM methods. The results revealed the energetic characteristics of the TS, which were in satisfactory agreement with NMR, and the corresponding TS geometries, which are not available from experiment. The most remarkable feature of the cis/trans-rotamerisation is that the amide nitrogen in AcProOH and AcHypOH adopts a tetrahedral geometry in the TS, Various HF, DFT, and MP2 calculations together with implicit solvation modeling were employed in order to identify the most suitable QM protocols for reliable predictions of the geometry and the relative energies of the conformations of Pro and Hyp containing peptides in aqueous solution. Solution NMR results were used for the verification of the reliability of the QM predictions. The results indicate that the MP2 calculations combined with implicit solvation models are reasonably accurate in reproducing NMR measured populations of four different conformations of either AcProOH or AcHypOH in different solvents, whereas HF and DFT B3LYP calculations were significantly less accurate.