Li H, Kennedy S D, Goldstein B M
Department of Biophysics, University of Rochester Medical Center, New York 14642.
Acta Crystallogr B. 1993 Aug 1;49 ( Pt 4):729-38. doi: 10.1107/s0108768193001053.
Isotiazofurin (C9H12N2O5S, NSC363223) is a thiazole nucleoside analogue of the antitumour agent tiazofurin. The conformation of this analogue has been studied using a variety of experimental and computational techniques. The crystal and molecular structure of isotiazofurin has been determined using single-crystal X-ray diffraction techniques and refined to a conventional R value of 0.030 for all data. Conformational features conserved in other thiazole nucleoside structures are also observed in the solid-state structure of isotiazofurin. The C-glycosidic torsion angle remains in the anti conformation and the carboxamide amino group remains cis-planar to the ring nitrogen. Ab initio calculations at the RHF/321G*@321G* level and natural bond orbital analysis of the results suggest that the carboxamide cis-planar conformation observed in the solid state is maintained in solution. However, semiempirical calculations suggest that a syn conformation about the C-glycosidic bond is energetically favored. This is supported by 1H nuclear Overhauser enhancement (NOE) studies. Analyses of NOE results using both slow- and rapid-exchange models indicate a preference for the syn conformation in solution. Thus, the anti conformation observed in the crystal structures of isotiazofurin is not maintained by isotiazofurin in solution.
异硫唑呋林（C9H12N2O5S，NSC363223）是抗肿瘤药物噻唑呋林的噻唑核苷类似物。已使用多种实验和计算技术研究了该类似物的构象。采用单晶X射线衍射技术测定了异硫唑呋林的晶体和分子结构，并对所有数据进行精修，使其常规R值达到0.030。在异硫唑呋林的固态结构中也观察到了其他噻唑核苷结构中保守的构象特征。C-糖苷扭转角保持反式构象，羧酰胺氨基与环氮保持顺式平面构象。在RHF/321G*@321G*水平上的从头算计算以及对结果的自然键轨道分析表明，固态中观察到的羧酰胺顺式平面构象在溶液中得以保持。然而，半经验计算表明，C-糖苷键的顺式构象在能量上更有利。1H核Overhauser增强（NOE）研究支持了这一点。使用慢速和快速交换模型对NOE结果进行分析表明，溶液中更倾向于顺式构象。因此，异硫唑呋林晶体结构中观察到的反式构象在溶液中并未被异硫唑呋林保持。
