Capecitabine (Xeloda) is a chemotherapy drug used to treat breast, gastric, and colorectal cancers. Commercial capecitabine crystallizes in the orthorhombic space group P212121 (#19) with a = 5.20587(3), b = 9.52324(4), c = 34.79574(21) Å, V = 1725.062(12) Å3, and Z = 4. A reduced cell search in the Cambridge Structural Database (Groom et al., Reference Groom, Bruno, Lightfoot and Ward2016) yielded three previous structure determinations (Rohlicek et al., Reference Rohlicek, Husak, Gavenda, Jegorov, Kratochvil and Fitch2016, BOVDUM; Malińska et al., Reference Malińska, Krzeczyński, Czerniec-Michalik, Trzcińska, Cmoch, Kutner and Woźniak2014, BOVDUM01 and BOVDUM02), using synchrotron powder data and later single-crystal data at two temperatures. The lattice parameters of the room temperature studies BOVDUM and BOVDUM01 are in excellent agreement with those determined here. The lattice parameters of BOVDUM02 (determined at 100 K) are smaller, by 2.43, 0.45, and 3.64% for a, b, and c, respectively. In this work, the sample was ordered from United States Pharmacopeial Convention (lot # G0J205), and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.413914 Å) powder diffraction data, density functional theory (DFT), and Rietveld refinement techniques. Hydrogen positions were included as part of the structure, and were re-calculated during the refinement. The diffraction data were collected on a beamline 11-BM at the Advanced Photon Source, Argonne National Laboratory. Figure 1 shows the powder X-ray diffraction pattern of the compound and the agreement of the refined and optimized structures. The agreement of the Rietveld-refined and DFT-optimized structures is poorest in the pentyl side chain, consistent with the disorder observed previously in BOVDUM and BOVDUM01. Pairwise comparisons of the two structures of this study and the three previous determinations shows that the root-mean-square Cartesian displacements of the non-hydrogen atoms lie in the range 0.18–0.53 Å, and that the differences are mainly in the side chains. The pattern is included in the Powder Diffraction File as entry 00-064-1493.
Figure 1. (Color online) Powder X-ray diffraction pattern of capecitabine. The Rietveld-refined structure is indicated in red, and the DFT-optimized structure is indicated in blue.
ACKNOWLEDGEMENTS
Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. This work was partially supported by the International Centre for Diffraction Data. We thank Lynn Ribaud and Saul Lapidus for their assistance in the data collection, and Andrey Rogachev for the use of computing resources at IIT.
SUPPLEMENTARY MATERIAL
The supplementary material for this article can be found at https://doi.org/10.1017/S0885715619000575
