Lal Jhajan, Prajapati Gurudayal, Meena Rachana, Kant Ruchir, Sankar Ampapathi Ravi, Reddy Damodara N
Division of Medicinal and Process Chemistry, CSIR-CDRI, Lucknow, 226031, India) .
Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, UP-201002, India.
Chem Asian J. 2023 Jan 3;18(1):e202201023. doi: 10.1002/asia.202201023. Epub 2022 Nov 29.
We report herein the first systematic crystal structural investigation of azaproline incorporated in homo- and heterochiral diprolyl peptides. The X-ray crystallography data of peptides 1-5 illustrates that stereodynamic nitrogen in azaproline adopted the stereochemistry of neighbouring proline residue without depending on its position in the peptide sequence. Natural bond orbital analysis of crystal structures indicates O -C' of peptides 4 and 5 participating in n→π* interaction with stabilization energy about 1.21-1.33 kcal/mol. Density functional theory calculations suggested that the endo-proline ring puckering favoured over exo-conformation by 6.72-7.64 kcal/mol. NBO and DFT data reveals that the n→π* interactions and proline ring puckering stabilize azaproline chirality with the neighbouring proline stereochemistry. The CD, solvent titration, variable-temperature and 2D NMR experimental results further supported the crystal structures conformation.
我们在此报告了对氮杂脯氨酸掺入同手性和异手性二脯氨酰肽中的首次系统晶体结构研究。肽1 - 5的X射线晶体学数据表明，氮杂脯氨酸中的立体动力学氮采用了相邻脯氨酸残基的立体化学结构，而不依赖于其在肽序列中的位置。晶体结构的自然键轨道分析表明，肽4和5的O - C'参与了n→π相互作用，稳定能约为1.21 - 1.33千卡/摩尔。密度泛函理论计算表明，内脯氨酸环的褶皱比外构象更有利，能量差为6.72 - 7.64千卡/摩尔。自然键轨道和密度泛函理论数据表明，n→π相互作用和脯氨酸环的褶皱通过相邻脯氨酸的立体化学稳定了氮杂脯氨酸的手性。圆二色光谱、溶剂滴定、变温和二维核磁共振实验结果进一步支持了晶体结构的构象。
