Scientific Research Center, Henan University of Chinese Medicine, Zhengzhou, China.
Population and Family Planning Science and Technology Research Institute of Henan, Zhengzhou, China.
Nucleosides Nucleotides Nucleic Acids. 2021;40(2):212-221. doi: 10.1080/15257770.2020.1861288. Epub 2020 Dec 18.
The conformational features of drugs are important with respect to their biological activity. In this report, we confirmed the solid-state conformation of 1-(4'-azido-2'-deoxy-2'-fluoro-β-d-arabinofuranosyl) cytosine using single-crystal X-ray crystallography and the conformations of three 2'-deoxy-2'-fluoro-4'-substituted nucleosides in solution using Altona-Haasnoot's equations and Nuclear Overhauser effect spectroscopy (NOESY). Furthermore, we compared the preferred solid-state and solution conformation of these nucleosides with thermodynamics cycles to obtain more evidence of their conformations. The results showed 1-(4'-azido-2'-deoxy-2'-fluoro--d-arabinofuranosyl) cytosine was south type conformation (C-3'-) in solid-state and three 4'-substituted nucleosides were north type conformations (C-3'-) in solution. The north type conformations in solution indicated these compounds were steady to acidic and enzymatic N-glycolysis.
药物的构象特征与其生物活性有关。在本报告中，我们通过单晶 X 射线晶体学证实了 1-(4'-叠氮-2'-脱氧-2'-氟-β-D-阿拉伯呋喃基)胞嘧啶的固态构象，并通过 Altona-Haasnoot 方程和核 Overhauser 效应光谱 (NOESY) 证实了三种 2'-脱氧-2'-氟-4'-取代核苷在溶液中的构象。此外，我们将这些核苷的优选固态和溶液构象与热力学循环进行了比较，以获得更多关于其构象的证据。结果表明，1-(4'-叠氮-2'-脱氧-2'-氟-β-D-阿拉伯呋喃基)胞嘧啶在固态中呈南式构象（C-3'-），而三种 4'-取代核苷在溶液中呈北式构象（C-3'-）。溶液中的北式构象表明这些化合物在酸性和酶促 N-糖酵解条件下稳定。
