title: Crystal structure and tautomerism of capecitabine.
abstract: The crystal and molecular structure of capecitabine, an anticancer pharmaceutical substance, was solved and refined using single-crystal X-ray diffraction. The compound was synthesized from a derivative of cytidine by a modified method. The crystal of capecitabine for X-ray study was grown by seedless crystallization from a single solvent. The low and room temperature single-crystal X-ray crystallographic study revealed that capecitabine exists in the solid state exclusively in one of the two possible prototropic tautomers. In the molecular structure of this tautomer, the hydrogen atom is attached to the N3 nitrogen atom of the pyrimidine ring (imine tautomer) and not to the N(4) nitrogen of the carbamate (carbamate tautomer), as has been widely reported up to the present. The imine tautomer was also found to be thermodynamically preferred in the ab initio calculations. This finding indicates that the reported structural formula of capecitabine, as well as its systematic chemical name, must be revised.
authors.affiliation: Department of Chemistry, University of Warsaw, Warszawa, 02-093, Poland.
authors.forename: Maura
authors.initials: M
authors.lastname: Malińska
authors.forename: Piotr
authors.initials: P
authors.lastname: Krzeczyński
authors.forename: Ewelina
authors.initials: E
authors.lastname: Czerniec-Michalik
authors.forename: Kinga
authors.initials: K
authors.lastname: Trzcińska
authors.forename: Piotr
authors.initials: P
authors.lastname: Cmoch
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kutner
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Woźniak
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry*; D000069287:Capecitabine; D003460:Crystallization; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D000438:Alcohols; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
keywords: X-ray crystallography; ab initio calculations; capecitabine; stability; structure; tautomerism