Structure solution of low-temperature simvastatin polymorphs from synchrotron powder diffraction
M. Husak, Bohumil Kratochvíl, A. Jegorov · Acta Crystallographica Section A Foundations of Crystallography · 2008
Capecitabine is the first FDA-approved oral chemotherapy for the treatment for some types of cancer, including advanced bowel cancer or breast cancer.Capecitabine is 5-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine, and in vivo is enzymatically converted to the active drug 5-fluorouracil.Crystal structure determination of capecitabine was not apparently reported yet.The crystal structure of capecitabine was determined from high-resolution x-ray synchrotron powder diffraction data using parallel tempering method combined with grid computing technique.Data was collected on synchrotron ESRF in Grenoble on beam line ID31.Capecitabine crystallizes in P212121 space group, Z=4, with unit cell parameters a=5.21, b=9.52, c=34.79,V=1724.The initial model was generated by AM1 computing method implemented in program MOPAC.The structure was solved in program FOX which was modified for grid computing techniques -FoxGrid.The initial model was restrained with bonds and angles restrains.This reduction allowed the parallel tempering to complete within a reasonable computation time.The most probably result in consideration of chemical validity (crystal packing and hydrogen-bonding pattern) was selected for refinement.The structure was refined in program GSAS.The final refinement, treated molecule of capecitabine as relaxed molecule with bonds and angles restrains, leads to final confidence factors Rp=0.096 and Rwp=0.158.This study was supported by the grant of the Czech Grant Agency (GACR 203/07/0040), grant from the Grant Agency of the Academy of Sciences of the Czech Republic (IAA400500602) and by the research program MSM6046137302 of the Ministry of Education,Youth and Sports of the Czech Republic.