Blanton, Thomas N.

Gindhart, Amy M.

Golab, Joseph T.

Kaduk, James A.

Patel, Nilan V.

English

Illinois Mathematics and Science Academy: DigitalCommons@IMSA

DATA REPORTPowder X-ray diffraction of flucytosine, C4H4FN3ONilan V. Patel,1 Joseph T. Golab,1 James A. Kaduk ,2,3,a) Amy M. Gindhart,4 and Thomas N. Blanton 41Illinois Mathematics and Science Academy, 1500 Sullivan Rd., Aurora, Illinois 60506-1000, USA2Illinois Institute of Technology, 3101 S. Dearborn St., Chicago, Illinois 60616, USA3North Central College, 131 S. Loomis St., Naperville, Illinois 60540, USA4ICDD, 12 Campus Blvd., Newtown Square, Pennsylvania 19073-3273, USA(Received 30 November 2019; accepted 8 December 2019)Flucytosine, CAS #2022-85-7, crystallizes in the tetragonal space group P41212 (#94) with a =6.643768(27), c = 23.89009(10) Å, V = 1054.500(7) Å3, and Z = 8. In this work, the sample wasobtained from the United States Pharmacopeial Convention (USP) Lot #R03100 and analyzedas-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ =0.412826 Å) powder diffraction data and optimized using the density functional theory (DFT).When looking down the a-axis, the crystal structure consists of multiple ribbon-like structures stackedinto columns. The powder X-ray diffraction pattern of the compound has been submitted to ICDD®for inclusion in the Powder Diffraction File™ (PDF®). The agreement of the Rietveld-refined andDFT-optimized structures is good, with the largest difference in the external amine group with anoverall root mean displacement of 0.056 Å. There is also evidence of unit cell expansion at highertemperatures, as the volume of the unit cell at 298 K was 1.6–1.9% greater than the two unit cellsobtained at 150 K. A N–H⋯O hydrogen bond exists in the inter-ribbon region between the flucyto-sine molecules, resulting in a 3D hydrogen bond network. © 2020 International Centre for DiffractionData. [doi:10.1017/S0885715619000903]Key words: flucytosine, Ancobon, Rietveld refinement, density functional theoryFlucytosine, also called 5-fluorocytosine (commercial nameAncobon), is an antifungal drug used to treat Candida(yeast) and cryptococcosis infections. Flucytosine, CAS#2022-85-7, crystallizes in the tetragonal space groupP41212 (#94) with a = 6.643768(27), c = 23.89009(10) Å,V = 1054.500(7) Å3, and Z = 8. A reduced cell search in theCambridge Structural Database (Groom et al., 2016) yieldedone previous structure determination (Hulme and Tocher,2006), using single-crystal X-ray diffraction collected at150 K. A powder pattern calculated from this crystal structureis included in the Powder Diffraction file as entry02-090-1047. Powder diffraction patterns calculated fromlow-temperature, single-crystal data typically have diffractionpeaks with 2θ positions that differ from room temperaturepowder diffraction data. These differences subsequently hin-der phase identification at room temperature, thus the needfor high-quality, room temperature X-ray diffraction data(Kaduk et al., 2014).In this work, the sample was obtained from the UnitedStates Pharmacopeial Convention (USP) Lot #R03100 andanalyzed as-received. The diffraction data were collected onbeamline 11-BM at the Advanced Photon Source atArgonne National Laboratory. The room temperature (295K) crystal structure was refined using synchrotron (λ =0.412826 Å) powder diffraction data and optimized usingthe density functional theory (DFT). Hydrogen positionswere also included as a part of the structure and werere-calculated during the refinement (Figure 1).The agreement of the Rietveld-refined and DFT-optimized structures is good, with the largest difference inthe external amine group with an overall root-mean-squareddisplacement of 0.056 Å. When looking down the a-axis,the crystal structure consists of multiple ribbon-like structuresstacked into columns. There is also evidence of unit cellexpansion at higher temperatures, as the volume of the unitcell at 295 K was 1.6–1.9% greater than the unit cells obtainedat 150 K. We noticed similar hydrogen bonding between thestructures at 150 K and 298 K. Specifically, we also found theN1–H2⋯O1 hydrogen bond that exists in the inter-ribbon regionbetween the flucytosine molecules, resulting in a 3D hydrogenbond network. The powder X-ray diffraction pattern of the com-pound has been submitted to ICDD® for inclusion in the PowderDiffraction File™ (PDF®; Gates and Blanton, 2019).ACKNOWLEDGEMENTSThe authors thank the SIR Department at the Illinois Mathand Science Academy for offering us this research opportunity.FUNDING INFORMATIONThe use of the Advanced Photon Source at ArgonneNational Laboratory was supported by the U.S. Departmentof Energy, Office of Science, and Office of Basic EnergySciences under Contract No. DE-AC02-06CH11357. Thiswork was supported by the International Centre forDiffraction Data (ICDD).a)Author to whom correspondence should be addressed. Electronic mail:kaduk@polycrystallography.com67 Powder Diffraction 35 (1), March 2020 0885-7156/2020/35(1)/67/2/$18.00 © 2020 JCPDS-ICDD 67DEPOSITED DATACIF and/or RAW data files were deposited with ICDD.You may request this data from ICDD at info@icdd.com.Gates-Rector, S. and Blanton, T. (2019). “The Powder Diffraction File: a qual-ity materials characterization database,” Powder Diffr. 34(4), 352–360.Groom, C. R., Bruno, I. J., Lightfoot, M. P., and Ward, S. C. (2016). “TheCambridge Structural Database,” Acta Crystallogr. B. 72, 171–179.Hulme, A. T. and Tocher, D. A. (2006). “The discovery of new crystal formsof 5-fluorocytosine consistent with the results of computational structureprediction,” Cryst. Growth Des. 6, 481–487.Kaduk, J. A., Crowder, C. E., Zhong, K., Fawcett, T. G., and Suchomel, M. R.(2014). “Crystal structure of atomoxetine hydrochloride (Strattera),C17H22NOCl,” Powder Diffr. 29(3), 269–273.Figure 1. (Colour online) Powder X-ray diffraction pattern of flucytosine. The Rietveld refinement structure is indicated in red, and the DFT-optimized structureis indicated in blue.68 Powder Diffr., Vol. 35, No. 1, March 2020 Patel et al. 68

Powder X-ray diffraction of flucytosine, C4H4FN3O

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Powder X-ray diffraction of flucytosine, C4H4FN3O

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