Solid-state and solution conformations of isotiazofurin: crystallographic, computational and 1H NMR studies.
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.
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Department of Biophysics, University of Rochester Medical Center, New York 14642.
Kennedy
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Goldstein
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D000970:Antineoplastic Agents / Q000737:chemistry*; D006860:Hydrogen Bonding; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D012254:Ribavirin / Q000031:analogs & derivatives / Q000737:chemistry; D012263:Ribonucleosides / Q000737:chemistry*; D012996:Solutions; D013844:Thiazoles / Q000737:chemistry*; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D012263:Ribonucleosides; D012996:Solutions; D013844:Thiazoles; D012254:Ribavirin; C083363:isotiazofurin; C033706:tiazofurin