Crystal structure of clofarabine (form I), C10H11ClFN5O3, from synchrotron power diffraction data and density functional theory calculations

Salazar, J.K.; Kaduk, J.A.; Dosen, A.; Blanton, T.N.

doi:10.1107/S2056989026006584

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ISSN: 2056-9890

Volume 82| Part 7| July 2026| Pages 883-887

https://doi.org/10.1107/S2056989026006584

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Crystal structure of clofarabine (form I), C₁₀H₁₁ClFN₅O₃, from synchrotron power diffraction data and density functional theory calculations

Jacob K. Salazar,^a James A. Kaduk,^b,^c ^* Anja Dosen ^d and Thomas N. Blanton ^e

^aNorth Central College, Department of Chemistry, 131 S. Loomis St., Naperville IL 60540, USA, ^bNorth Central College, Department of Physics, 131 S. Loomis St., Naperville IL 60540, USA, ^cDepartment of Chemistry, Illinois Institute of Technology, 3101 S. Dearborn St., Chicago IL 60616, USA, ^dICDD, 12 Campus Blvd., Newtown Square, PA 19073-3273, USA, and ^eICDD, 12 Campus Blvd., Newtown Square, PA 19073-327,3 , USA
^*Correspondence e-mail: [email protected]

Edited by W. T. A. Harrison, University of Aberdeen, United Kingdom (Received 30 April 2026; accepted 22 June 2026; online 26 June 2026)

The crystal structure of clofarabine (form I) [systematic name: 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine], C₁₀H₁₁ClFN₅O₃, has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. The oxolane ring adopts an envelope conformation and the angle between the mean ring planes is 88.4 (2)°, resulting in an L-shaped molecule. The molecules stack along the short a-axis direction, and N—H⋯O, O—H⋯N and N—H⋯N hydrogen bonds link them into a three-dimensional network.

Keywords: powder diffraction; clofarabine; Clolar; Rietveld refinement; density functional theory.

CCDC references: 2564142; 2564141

1. Chemical context

Clofarabine, C₁₀H₁₁ClFN₅O₃ (marketed as Clolar, Evoltra and Clofarex in different countries) is a purine nucleoside antimetabolite, used to treat relapsed or refractory acute lymphoblastic leukemia in children and young adults (Bonate et al., 2006 ). Clofarabine is administered intravenously and functions by inhibiting DNA synthesis and ribonucleoside reductase. The systematic name (CAS Registry Number 123318-82-1) is (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol.

A powder pattern for clofarabine (form I) has been reported in Chinese Patent CN101407640A (Xia et al., 2011 ). Un-named crystalline forms of clofarabine are claimed in US Patent 5,034,518 (Montgomery & Secrist, 1991 ; Southern Research Institute) and US Patent 5,661,136 (Montgomery & Secrist, 1997 ; Southern Research Institute). Xia et al. suggest that these earlier forms were monohydrates, and claim that their form is new. The present work was carried out as part of a project (Kaduk et al., 2014 ) to determine the crystal structures of large-volume commercial pharmaceuticals, and includes high-quality powder diffraction data for them in the Powder Diffraction File (Kabekkodu et al., 2024 ).

2. Structural commentary

The synchrotron X-ray powder pattern of clofarabine is similar enough to that reported by Xia et al. (2011) for form I (Fig. 1) to conclude that they represent the same material. The patent pattern exhibits significant displacement/transparency peak position errors, as well as substantial preferred orientation.

Figure 1
Comparison of the synchrotron pattern of clofarabine Form I (black) to that reported by Xia et al. (2011

) using Cu Kα radiation (green) converted to the synchrotron wavelength of 0.4687342 Å. The patent pattern (measured using Cu Kα radiation) was digitized using UN-SCAN-IT (Silk Scientific, 2013

) and converted to the synchrotron wavelength of 0.4687342 Å using JADE Pro (MDI, 2025

). Image generated using JADE Pro (MDI, 2025

The mean plane of the C16–C20/N6–N9 purine ring system of the asymmetric molecule lies approximately in the (12 $[\overline{2}]$ ) Miller plane, and the mean plane of the C11–C14/O3 oxolane ring is aligned approximately with ( $[\overline{1}]$ 22). The latter ring adopts an envelope conformation with atom C12 as the flap. The angle between the mean ring planes is 88.4 (2)°, so the molecules may be described as L-shaped (Fig. 2). The root-mean-square difference of the non-H atoms in the Rietveld-refined and VASP-optimized structures of clofarabine, calculated using the Mercury (Macrae et al., 2020 ) CSD-Materials/search/crystal packing similarity tool is 0.078 Å (Fig. 3); the structures are essentially identical. The root-mean-square Cartesian displacement of the non-H atoms in the refined and optimized structures, calculated using the Mercury Calculate molecule overlay tool, is 0.048 Å (Fig. 4). The agreements are within the normal range for correct structures (van de Streek & Neumann, 2014 ). The remaining discussion will emphasize the VASP-optimized structure.

Figure 2
The molecular structure of clofarabine, showing 50% probability spheroids/ellipsoids.

Figure 3
Comparison of the Rietveld-refined (colored by atom type) and VASP-optimized (pale green) structures of clofarabine, calculated using the Mercury CSD-Materials/Search/Crystal Packing Similarity tool. The root-mean-square Cartesian displacement is 0.078 Å.

Figure 4
Comparison of the refined structure of clofarabine (red) to the VASP-optimized structure (blue). The comparison was generated using the Mercury Calculate/Molecule Overlay tool; the r.m.s. difference is 0.048 Å.

All of the bond distances, bond angles, and torsion angles fall within the normal ranges indicated by a Mercury Mogul geometry check (Macrae et al., 2020). Quantum chemical geometry optimization of the isolated clofarabine molecule (DFT/B3LYP/6-31G*/water) using Spartan '24 (Wavefunction, 2025 ) indicated that the observed conformation is 5.2 kcal mol⁻¹ higher in energy than a local minimum, which has a very similar conformation. The global minimum-energy conformation is 14.8 kcal mol⁻¹ lower in energy, but is folded on itself to form intramolecular O—H⋯N hydrogen bonds. Intermolecular interactions are thus important in determining the observed solid-state conformation.

3. Supramolecular features

Viewed down the short a-axis direction (Fig. 5) the structure exhibits discrete clofarabine molecules. When viewed down the c-axis direction (Fig. 6) a herringbone arrangement of molecules is apparent. The shortest ring centroid–ring centroid distance is 5.067 (2) Å, as the molecules stack along the a-axis direction.

Figure 5
Crystal structure of clofarabine, viewed down the a axis.

Figure 6
Crystal structure of clofarabine, viewed down the c axis.

Analysis of the contributions to the total crystal energy of the structure using the Forcite module of Materials Studio (Dassault Systèmes, 2025 ) indicated that the intramolecular energy is dominated by angle distortion terms, as might be expected for a molecule containing a fused ring system. The intermolecular energy is dominated by van der Waals attractions, which in this force-field based analysis include hydrogen bonds. The hydrogen bonds are better discussed using the results of the DFT calculation.

There are several hydrogen bonds in the structure (Table 1). The amino group N10 acts as a donor in two classical hydrogen bonds, one to the hydroxyl group O4 and to another amino group N10. The energy of the N10—H30⋯O4 hydrogen bond is 5.6 kcal mol⁻¹, calculated using the correlation of Wheatley & Kaduk (2019 ). The hydroxyl groups O4 and O5 form strong O—H⋯N hydrogen bonds to the ring N atoms N7 and N8, respectively. These link the molecules into chains along the b-axis direction, with graph set descriptors (Etter, 1990 ; Bernstein et al., 1995 ; Motherwell et al., 2000 ) C₁¹(8), C₁¹(9) and C₂²(11). The N—H⋯O and N—H⋯N hydrogen bonds link the molecules along the c-axis direction, with graph sets C₁¹(10) and C₁¹(2). These and other larger patterns result in a three-dimensional hydrogen bond network. Four intra- and inter-molecular C—H⋯O hydrogen bonds also contribute to the lattice energy.

Table 1
Hydrogen-bond geometry (Å, °) for clofarabine_VASP

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H28⋯N7ⁱ	1.01	1.72	2.726	173
O5—H29⋯N8ⁱⁱ	0.99	1.86	2.831	167
N10—H30⋯O4ⁱⁱⁱ	1.03	1.87	2.854	159
N10—H31⋯N10^iv	1.02	2.38	3.271	145
C11—H21⋯F2^v	1.10	2.27	3.208	142
C11—H21⋯O5^vi	1.10	2.60	3.531	142
C12—H22⋯O3^vii	1.10	2.40	3.396	149
C15—H26⋯Cl1^viii	1.11	2.77	3.570	129
C17—H27⋯F2^ix	1.09	2.40	3.177	127
Symmetry codes: (i) $[-x+2, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (iii) $[-x+{\script{3\over 2}}, -y, z-{\script{1\over 2}}]$ ; (iv) $[x+{\script{1\over 2}}, -y-{\script{1\over 2}}, -z]$ ; (v) ; (vi) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (vii) ; (viii) $[-x+{\script{1\over 2}}, -y, z+{\script{1\over 2}}]$ ; (ix) $[-x+2, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

The volume enclosed by the Hirshfeld surface of clofarabine (Fig. 7; Hirshfeld, 1977 ; Spackman et al., 2021 ) is 299.22 Å³ or 97.94% of 1/4 of the unit-cell volume. The packing density is thus typical. The only significant close contacts (red in Fig. 9) involve the hydrogen bonds. The volume/non-hydrogen atom is smaller than normal, at 15.3 Å³.

Figure 7
The Hirshfeld surface of clofarabine. Intermolecular contacts longer than the sums of the van der Waals radii are colored blue, and contacts shorter than the sums of the radii are colored red. Contacts equal to the sums of radii are white.

The Bravais–Friedel–Donnay–Harker (Bravais, 1866 ; Friedel, 1907 ; Donnay & Harker, 1937 ) algorithm suggests that we might expect elongated morphology for crystallites of clofarabine, with [100] as the long axis. A second-order spherical harmonic model for preferred orientation was included. The texture index was 1.017, indicating that the preferred orientation was slight in this rotated capillary specimen.

4. Database survey

A reduced cell search in the Cambridge Structural Database (CSD, 2026.1.0; Groom et al., 2016 ), combined with the chemistry C, H, Cl, F, N, and O only, yielded no hits.

5. Synthesis and crystallization

Clofarabine is a commercial reagent, purchased from TargetMol (Batch #132343), and was used as-received.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The white powder was packed into a 1.5 mm diameter Kapton capillary, and rotated during the measurement at ∼50 Hz. The powder pattern was measured at 295 K at beam line 11-BM (Lee et al., 2008 ; Wang et al., 2008 ; Antao et al., 2008 ) of the Advanced Photon Source at Argonne National Laboratory using a wavelength of 0.4687342 Å from 0.5–50° 2θ with a step size of 0.001° and a counting time of 0.1 sec step⁻¹. The high-resolution powder diffraction data were collected using twelve silicon crystal analyzers that allow for high angular resolution, high precision, and accurate peak positions. A mixture of silicon (NIST SRM 640c) and alumina (NIST SRM 676a) standards (ratio Al₂O₃:Si = 2:1 by weight) was used to calibrate the instrument and refine the monochromatic wavelength used in the experiment.

Table 2
Experimental details

	clofarabine
Crystal data
Chemical formula	C₁₀H₁₁ClFN₅O₃
M_r	303.68
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	295
a, b, c (Å)	5.067481 (12), 10.79402 (2), 22.34124 (5)
V (Å³)	1222.03 (1)
Z	4
Radiation type	Synchrotron, λ = 0.46873 Å
μ (mm⁻¹)	0.04
Specimen shape, size (mm)	Cylinder, 2.0 × 1.5

Data collection
Diffractometer	11-BM, APS
Specimen mounting	Kapton capillary
Data collection mode	Transmission
Scan method	Step
2θ values (°)	2θ_min = 0.510, 2θ_max = 49.995, 2θ_step = 0.001

Refinement
R factors and goodness of fit	R_p = 0.072, R_wp = 0.085, R_exp = 0.041, R(F²) = 0.06753, χ² = 4.439
No. of parameters	92
No. of restraints	56
(Δ/σ)_max	13.147
Computer programs: GSAS-II (Toby & Von Dreele, 2013) and DIAMOND (Brandenburg & Putz, 2025 ).

The pattern was indexed on a primitive orthorhombic unit cell with a = 5.06685, b = 10.79310, c = 22.33892 Å, V = 1225.6 Å³, and Z = 4 using N-TREOR as incorporated into EXPO2014 (Altomare et al., 2013 ). The suggested space group was P2₁2₁2₁, which was confirmed by the successful solution and refinement of the structure.

The molecular structure of clofarabine was downloaded from PubChem (Kim et al., 2023 ) as Conformer3D_COMPOUND_CID_119182.sdf. It was converted to a *.mol2 file using Mercury (Macrae et al., 2020), and to a Fenske–Hall Z-matrix using OpenBabel (O'Boyle et al., 2011 ). The structure was solved using parallel tempering techniques as implemented in FOX (Favre-Nicolin & Černý, 2002 ).

Rietveld refinement was carried out using GSAS-II (Toby & Von Dreele, 2013 ). Only the 2.0–35.0° portion of the pattern was included in the refinements (d_min = 0.779 Å). All non-H bond distances and angles were subjected to restraints, based on a Mercury Mogul geometry check (Sykes et al., 2011 ; Bruno et al., 2004 ). The Mogul average and standard deviation for each quantity were used as the restraint parameters. The aromatic fused ring system was restrained to be planar. The restraints contributed 1.4% to the overall χ². The hydrogen atoms were included in calculated positions, which were recalculated during the refinement using Materials Studio (Dassault Systèmes, 2025). The Cl atom was refined anisotropically. The other U_iso(H) values were grouped by chemical similarity. The peak profiles were described using the generalized microstrain model (Stephens, 1999 ). The background was modeled using a six-term shifted Chebyshev polynomial, with a peak at 5.89° to model the scattering from the Kapton capillary and any amorphous component of the sample.

The final refinement of 92 variables using 33,001 observations and 56 restraints yielded the residuals R_wp = 0.0856 and GOF = 2.11. The largest peak (0.65 Å from Cl1) and hole (0.36 Å from Cl1) in the difference-Fourier map are 0.459 (12) and −0.594 (12) e Å⁻³, respectively. The final Rietveld plot is shown in Fig. 8. The largest features in the normalized error plot are in the positions and shapes of some of the strong low-angle peaks, and may indicate a change in the specimen during the measurement.

Figure 8
The Rietveld plot for clofarabine. The blue crosses represent the observed data points, and the green line is the calculated pattern. The cyan curve is the normalized error plot, and the red line is the background curve. The blue tick marks indicate the peak positions. The vertical scale has been multiplied by a factor of 20× for 2θ > 15.5°.

The crystal structure of clofarabine was optimized (fixed experimental unit cell) with density functional theory techniques using VASP (Kresse & Furthmüller, 1996 ) through the MedeA graphical interface (Materials Design, 2024 ). The calculation was carried out on 32 cores of a 144-core (768 Gb memory) HPE Superdome Flex 280 Linux server at North Central College. The calculation used the GGA-PBE functional, a plane wave cutoff energy of 400.0 eV, and a k-point spacing of 0.5 Å⁻¹ leading to a 3 × 2 × 1 mesh, and took ∼8.1 h. Single-point density functional theory calculations (fixed experimental cell) and population analysis were carried out using CRYSTAL23 (Erba et al., 2023 ). Fixed experimental cell) and population analysis were carried out using CRYSTAL17 (Dovesi et al., 2018 ). The basis sets for the H, C, N and O atoms in the calculation were those of Gatti et al. (1994 ), and those for F and Cl were those of Peintinger et al. (2013 ). The calculations were run on a 3.5 GHz PC using 8 k-points and the B3LYP functional, and took ∼1.4 h.

Supporting information

CCDC references: 2564142; 2564141

Crystal structure: contains datablocks clofarabine, clofarabine_VASP. DOI: https://doi.org/10.1107/S2056989026006584/hb8221sup1.cif

checkCIF report

Computing details top

2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine (clofarabine) top

Crystal data top

C₁₀H₁₁ClFN₅O₃	Z = 4
M_r = 303.68	D_x = 1.651 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Synchrotron radiation, λ = 0.46873 Å
a = 5.067481 (12) Å	µ = 0.04 mm⁻¹
b = 10.79402 (2) Å	T = 295 K
c = 22.34124 (5) Å	cylinder, 2.0 × 1.5 mm
V = 1222.03 (1) Å³

Data collection top

11-BM, APS diffractometer	Scan method: step
Specimen mounting: Kapton capillary	2θ_min = 0.510°, 2θ_max = 49.995°, 2θ_step = 0.001°
Data collection mode: transmission

Refinement top

Least-squares matrix: full	92 parameters
R_p = 0.072	56 restraints
R_wp = 0.085	16 constraints
R_exp = 0.041	Weighting scheme based on measured s.u.'s
R(F²) = 0.06753	(Δ/σ)_max = 13.147
49486 data points	Background function: Background function: "chebyschev-1" function with 6 terms: 42.46(6), -8.82(9), -9.57(8), 2.83(8), -1.00(7), 2.56(7), Background peak parameters: pos, int, sig, gam: 5.889(10), 4.22(8)e3, 4.12(15)e3, 0.100,
Profile function: Finger-Cox-Jephcoat function parameters U, V, W, X, Y, SH/L: peak variance(Gauss) = Utan(Th)²+Vtan(Th)+W: peak HW(Lorentz) = X/cos(Th)+Ytan(Th); SH/L = S/L+H/L U, V, W in (centideg)², X & Y in centideg 1.163, -0.126, 0.063, 0.000, 0.000, 0.002,	Preferred orientation correction: Simple spherical harmonic correction Order = 2 Coefficients: 0:0:C(2,0) = -0.2134(29); 0:0:C(2,2) = 0.199(4)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.0189 (2)	0.16598 (9)	0.02919 (5)	0.0491
F2	0.8827 (3)	0.21882 (16)	0.24051 (9)	0.0404 (4)*
O3	0.3887 (4)	0.0218 (2)	0.29218 (10)	0.0404 (4)*
O4	0.8336 (4)	0.1997 (2)	0.38062 (10)	0.0404 (4)*
O5	0.7624 (5)	−0.1464 (2)	0.33800 (11)	0.0543 (8)*
N6	0.5950 (5)	0.0280 (2)	0.19828 (9)	0.0276 (3)*
N7	0.8275 (5)	−0.1145 (2)	0.14655 (11)	0.0276 (3)*
N8	0.3110 (5)	0.1027 (2)	0.11892 (10)	0.0276 (3)*
N9	0.3786 (5)	−0.0050 (2)	0.02505 (9)	0.0276 (3)*
N10	0.7125 (5)	−0.1486 (2)	0.01227 (11)	0.0276 (3)*
C11	0.4845 (5)	0.1019 (2)	0.24741 (11)	0.0404 (4)*
C12	0.7673 (5)	0.1167 (3)	0.33294 (12)	0.0404 (4)*
C13	0.6750 (5)	0.1895 (2)	0.27873 (12)	0.0404 (4)*
C14	0.5214 (6)	0.0417 (3)	0.34917 (13)	0.0404 (4)*
C15	0.5802 (7)	−0.0816 (3)	0.37589 (16)	0.0543 (8)*
C16	0.5031 (5)	0.0297 (3)	0.14087 (9)	0.0276 (3)*
C17	0.7914 (6)	−0.0585 (3)	0.19924 (11)	0.0276 (3)*
C18	0.6444 (6)	−0.0584 (3)	0.11009 (10)	0.0276 (3)*
C19	0.5783 (6)	−0.0731 (3)	0.04870 (10)	0.0276 (3)*
C20	0.2718 (6)	0.0791 (3)	0.06104 (11)	0.0276 (3)*
H21	0.30900	0.14393	0.23107	0.0526*
H22	0.93174	0.06037	0.32382	0.0526*
H23	0.57838	0.27853	0.28915	0.0526*
H24	0.38326	0.09796	0.37362	0.0526*
H25	0.40893	−0.13251	0.38656	0.0706*
H26	0.68813	−0.06089	0.41746	0.0706*
H27	0.89907	−0.08325	0.23913	0.0358*
H28	0.97473	0.25980	0.36946	0.0526*
H29	0.75868	−0.23048	0.35566	0.0706*
H30	0.66866	−0.15293	−0.03273	0.0358*
H31	0.82978	−0.21654	0.02850	0.0358*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0463 (9)	0.0535 (9)	0.0474 (10)	0.0085 (15)	−0.0268 (15)	0.0218 (16)

Geometric parameters (Å, º) top

Cl1—C20	1.740 (2)	C14—C12	1.529 (3)
F2—C13	1.392 (2)	C14—C15	1.489 (3)
O3—C11	1.408 (3)	C14—H24	1.076 (3)
O3—C14	1.456 (3)	C15—O5	1.435 (4)
O4—C12	1.432 (3)	C15—C14	1.489 (3)
O4—H28	0.997 (2)	C15—H25	1.055 (4)
O5—C15	1.435 (4)	C15—H26	1.101 (4)
O5—H29	0.990 (2)	C16—N6	1.365 (2)
N6—C11	1.468 (3)	C16—N8	1.345 (2)
N6—C16	1.365 (2)	C16—C18	1.375 (2)
N6—C17	1.364 (2)	C17—N6	1.364 (2)
N7—C17	1.336 (3)	C17—N7	1.336 (3)
N7—C18	1.375 (2)	C17—H27	1.079 (2)
N8—C16	1.345 (2)	C18—N7	1.375 (2)
N8—C20	1.333 (2)	C18—C16	1.375 (2)
N9—C19	1.357 (2)	C18—C19	1.421 (3)
N9—C20	1.328 (2)	C19—N9	1.357 (2)
N10—C19	1.338 (3)	C19—N10	1.338 (3)
N10—H30	1.031 (2)	C19—C18	1.421 (3)
N10—H31	1.011 (2)	C20—Cl1	1.740 (2)
C11—O3	1.408 (3)	C20—N8	1.333 (2)
C11—N6	1.468 (3)	C20—N9	1.328 (2)
C11—C13	1.522 (2)	H21—C11	1.064 (3)
C11—H21	1.064 (3)	H22—C12	1.052 (3)
C12—O4	1.432 (3)	H23—C13	1.103 (3)
C12—C13	1.518 (2)	H24—C14	1.076 (3)
C12—C14	1.529 (3)	H25—C15	1.055 (4)
C12—H22	1.052 (3)	H26—C15	1.101 (4)
C13—F2	1.392 (2)	H27—C17	1.079 (2)
C13—C11	1.522 (2)	H28—O4	0.997 (2)
C13—C12	1.518 (2)	H29—O5	0.990 (2)
C13—H23	1.103 (3)	H30—N10	1.031 (2)
C14—O3	1.456 (3)	H31—N10	1.011 (2)

C11—O3—C14	111.81 (18)	C12—C13—H23	114.8 (2)
C12—O4—H28	112.9 (2)	O3—C14—C12	104.3 (2)
C15—O5—H29	101.5 (3)	O3—C14—C15	108.1 (3)
C11—N6—C16	124.40 (19)	C12—C14—C15	113.9 (3)
C11—N6—C17	129.7 (2)	O3—C14—H24	103.1 (2)
C16—N6—C17	105.86 (14)	C12—C14—H24	110.6 (3)
C17—N7—C18	103.30 (17)	C15—C14—H24	115.5 (3)
C16—N8—C20	110.43 (17)	O5—C15—C14	109.2 (3)
C19—N9—C20	115.96 (16)	O5—C15—H25	114.1 (3)
C19—N10—H30	120.8 (2)	C14—C15—H25	113.1 (3)
C19—N10—H31	121.5 (2)	O5—C15—H26	106.1 (3)
H30—N10—H31	116.3 (2)	C14—C15—H26	104.9 (3)
O3—C11—N6	109.2 (2)	H25—C15—H26	108.9 (3)
O3—C11—C13	105.89 (15)	N6—C16—N8	126.72 (15)
N6—C11—C13	116.1 (2)	N6—C16—C18	106.42 (13)
O3—C11—H21	102.6 (3)	N8—C16—C18	126.86 (15)
N6—C11—H21	107.12 (19)	N6—C17—N7	113.30 (17)
C13—C11—H21	115.0 (2)	N6—C17—H27	123.5 (2)
O4—C12—C13	110.0 (2)	N7—C17—H27	123.1 (3)
O4—C12—C14	110.2 (3)	N7—C18—C16	111.09 (15)
C13—C12—C14	102.26 (17)	N7—C18—C19	132.98 (18)
O4—C12—H22	108.7 (2)	C16—C18—C19	115.92 (15)
C13—C12—H22	112.9 (3)	N9—C19—N10	118.15 (19)
C14—C12—H22	112.7 (3)	N9—C19—C18	119.43 (17)
F2—C13—C11	109.8 (2)	N10—C19—C18	122.37 (19)
F2—C13—C12	112.0 (2)	Cl1—C20—N8	113.75 (17)
C11—C13—C12	103.89 (15)	Cl1—C20—N9	114.91 (16)
F2—C13—H23	105.51 (19)	N8—C20—N9	131.13 (19)
C11—C13—H23	110.9 (2)

(clofarabine_VASP) top

Crystal data top

C₁₀H₁₁ClFN₅O₃	c = 22.33879 Å
M_r = 360.68	V = 1221.61 Å³
Orthorhombic, P2₁2₁2₁	Z = 4
a = 5.06687 Å	D_x = 1.651 Mg m⁻³
b = 10.79280 Å

Data collection top

h = →	l = →
k = →

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	B_iso*/B_eq
Cl1	0.01212	0.16968	0.02898
F2	0.90535	0.21606	0.23899
O3	0.38561	0.02587	0.29060
O4	0.84115	0.19497	0.38208
O5	0.75419	−0.14849	0.34117
N6	0.59832	0.02849	0.19629
N7	0.81396	−0.11960	0.14513
N8	0.31324	0.10597	0.11693
N9	0.37245	−0.00306	0.02375
N10	0.68616	−0.15566	0.00827
C11	0.49010	0.10293	0.24534
C12	0.77245	0.11804	0.33283
C13	0.69128	0.18783	0.27665
C14	0.52255	0.04396	0.34742
C15	0.57085	−0.08032	0.37626
C16	0.50115	0.03082	0.13866
C17	0.78576	−0.06389	0.19766
C18	0.63647	−0.06134	0.10719
C19	0.56958	−0.07502	0.04585
C20	0.26192	0.07985	0.05972
H21	0.33140	0.15735	0.22472
H22	0.93523	0.05413	0.32150
H23	0.59644	0.27638	0.28803
H24	0.39549	0.09995	0.37712
H25	0.37979	−0.12899	0.38061
H26	0.64633	−0.06322	0.42197
H27	0.88790	−0.08940	0.23872
H28	0.97473	0.25980	0.36946
H29	0.75849	−0.23464	0.35654
H30	0.65698	−0.14890	−0.03741
H31	0.85246	−0.20128	0.02116

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O4—H28···N7ⁱ	1.01	1.72	2.726	173
O5—H29···N8ⁱⁱ	0.99	1.86	2.831	167
N10—H30···O4ⁱⁱⁱ	1.03	1.87	2.854	159
N10—H31···N10^iv	1.02	2.38	3.271	145
C11—H21···F2^v	1.10	2.27	3.208	142
C11—H21···O5^vi	1.10	2.60	3.531	142
C12—H22···O3^vii	1.10	2.40	3.396	149
C15—H26···Cl1^viii	1.11	2.77	3.570	129
C17—H27···F2^ix	1.09	2.40	3.177	127

Symmetry codes: (i) −x+2, y+1/2, −z+1/2; (ii) −x+1, y−1/2, −z+1/2; (iii) −x+3/2, −y, z−1/2; (iv) x+1/2, −y−1/2, −z; (v) x−1, y, z; (vi) −x+1, y+1/2, −z+1/2; (vii) x+1, y, z; (viii) −x+1/2, −y, z+1/2; (ix) −x+2, y−1/2, −z+1/2.

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. We thank Saul Lapidus for his assistance in the data collection. We also thank the ICDD team – Megan Rost, Steve Trimble, and Dave Bohnenberger – for their contribution to research, sample preparation, and in-house XRD data collection and verification.

Funding information

Funding for this research was provided by: International Centre for Diffraction Data (grant No. 09-03).

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