Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-22T07:44:01.642Z Has data issue: false hasContentIssue false
  • English
  • Français

Crystal structure of palbociclib form A, C24H29N7O2

Published online by Cambridge University Press:  20 December 2024

Petr Buikin ,
Alexander Korlyukov ,
Ivan Ushakov ,
Alexander Goloveshkin ,
Elizaveta Kulikova  and
Anna Vologzhanina Open the ORCID record for Anna Vologzhanina [Opens in a new window]
Petr Buikin
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova str. 28, Moscow 119334, Russia Institute of General and Inorganic Chemistry RAS, Leninsky Prosp. 31, Moscow 119991, Russia
Alexander Korlyukov
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova str. 28, Moscow 119334, Russia
Ivan Ushakov
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova str. 28, Moscow 119334, Russia
Alexander Goloveshkin
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova str. 28, Moscow 119334, Russia
Elizaveta Kulikova
Affiliation:
Kurchatov Institute, National Research Center, Pl. Akad. Kurchatova 1, Moscow 123182, Russia
Anna Vologzhanina*
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova str. 28, Moscow 119334, Russia
*
a)Author to whom correspondence should be addressed. Electronic mail: ann.vologzhanina@gmail.com
Rights & Permissions [Opens in a new window]

Abstract

The crystal structure of palbociclib (C24H29N7O2) used as a medication for the treatment of breast cancer has been solved and refined using synchrotron radiation after density functional theory optimization. Palbociclib crystallizes in the monoclinic system (space group P21/c, #14) at room temperature with crystal parameters: a = 11.3133(2), b = 5.62626(9), c = 35.9299(9) Å, β = 101.5071(12), V = 2241.03(8) Å3, and Z = 4. The crystal structure contains infinite N–H⋯N bonded layers. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).

Keywords

palbociclibpowder diffractionRietveld refinement
Type
New Diffraction Data
Information
Powder Diffraction , Volume 39 , Issue 4 , December 2024 , pp. 270 - 274
Check for updates
Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press on behalf of International Centre for Diffraction Data

I. INTRODUCTION

Palbociclib (DrugBank No DB09073) is a piperazine pyridopyrimidine used to treat HER2-negative and HR-positive advanced or metastatic breast cancer (Ibrahim et al., Reference Ibrahim, Mullarney, Shanker, Spong and Wang2016). It is a second-generation cyclin-dependent inhibitor of the CDK4 and CDK6 kinases (Finn et al., Reference Finn, Dering, Conklin, Kalous, Cohen, Desai, Ginther, Atefi, Chen, Fowst, Los and Slamon2009; Rocca et al., Reference Rocca, Farolfi, Bravaccini, Schirone and Amadori2014). The systematic name is 6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}-7H,8H-pyrido[2,3-d]pyrimidin-7-one (C24H29N7O2). Figure 1 shows a two-dimensional molecular diagram of palbociclib.

Figure 1. The molecular structure of palbociclib.

Crystal structures of several palbociclib salts and a cocrystal are reported (Katiyar et al., Reference Katiyar, Ahamad, Dash, Tripathi, Arora and Thakur2021; Zhou et al., Reference Zhou, Duan, Qin, Huang, Hou, Chen, Zhu, Xu, Jin and Zhuang2023; Allu et al., Reference Allu, An, Park and Kim2024). Patents US10329290B2 and US10766895B2 also contain information about the characteristic peaks in the X-ray powder diffraction patterns (PXRDs) for two crystal forms of palbociclib free base (Fan et al., Reference Fan, Guo, Huang and Gu2019, Reference Fan, Guo, Huang and Gu2020). However, the patterns have not been indexed, neither have the crystal structures of a free base palbociclib been solved and reported to date. Herein, we report on the crystal structure of form A of palbociclib as obtained using synchrotron radiation. This work is part of a project for determination of crystal structures of pharmaceutical ingredients from powder diffraction patterns (Goloveshkin et al., Reference Goloveshkin, Korlyukov and Vologzhanina2021, Reference Goloveshkin, Kulikova, Novikov, Vologzhanina and Korlyukov2024; Buikin et al., Reference Buikin, Vologzhanina, Novikov and Korlyukov2024a, Reference Buikin, Korlyukov, Kulikova, Novikov and Vologzhanina2024b).

II. EXPERIMENTAL

Palbociclib substance was purchased from Clearsynth (CAS No. 571190-30-2) and used without any purification. The synchrotron PXRD data were recorded at X-ray structural analysis beamline (Belok/XSA) of Kurchatov Synchrotron Radiation Source (Svetogorov et al., Reference Svetogorov, Dorovatovskii and Lazarenko2020). Monochromatic radiation of wavelength 0.7500 Å was used to measure the pattern and then to determine the θ angles. The sample was placed in a cryoloop of 200 μm in size and rotated around the horizontal axis during the measurement, which made it possible to average the diffraction patterns according to the orientations of the sample. The diffraction pattern was collected by the 2D Rayonix SX165 detector, which was located at a distance of 250 mm with 18° tilt angle. Debye–Scherrer (transmission) geometry was used with a 400 μm beam size. The 2θ range was 0.32–38.125° with a step size of 0.005°. The total exposure time was 10 min. The two-dimensional powder diffraction pattern obtained on the detector was further integrated to the standard form of the dependence of the intensity on the scattering angle I(2θ) using Dionis software (Svetogorov, Reference Svetogorov2018). To calibrate the sample–detector distance, the polycrystalline LaB6 (NIST SRM 660a, Morris et al., Reference Morris, McMurdie, Evans, Paretzkin, Parker, Pyrros and Hubbard1984) was used as a standard with the known positions of the diffraction lines. The diffraction peaks were approximated by fundamental parameters with Gaussian 1/cos(θ) convolution as described at ‘Bruker TOPAS 5 User Manual’ (2014).

The powder pattern was indexed in the P-centered monoclinic unit cell with the Topas 5.0 software (Coelho, Reference Coelho2003; ‘Bruker TOPAS 5 User Manual’, 2014). The systematic absences suggested the space group P21/c, which was confirmed by successful solution and refinement of the structure. A molecular model of palbociclib was taken from bis(palbociclib) oxalate dihydrate crystal structure (Katiyar et al., Reference Katiyar, Ahamad, Dash, Tripathi, Arora and Thakur2021) and converted into a Fenske–Hall Z-matrix file using OpenBabel (O'Boyle et al., Reference O'Boyle, Banck, James, Morley, Vandermeersch and Hutchison2011). A simulated annealing algorithm of Topas 5.0 was applied to find the positions of non-hydrogen atoms of palbociclib in an asymmetric unit. The solution result was used as a starting geometry for the periodic density functional theory (DFT) calculations at the Perdew-Baron-Erzenhopf (PBE) exchange–correlation functional level with a fixed unit cell using VASP 5.4.1 (Kresse and Hafner, Reference Kresse and Hafner1993, Reference Kresse and Hafner1994; Kresse and Furthmüller, Reference Kresse and Furthmüller1996a, Reference Kresse and Furthmüller1996b). Atomic cores were described using PAW potentials (Blöchl, Reference Blöchl1994; Joubert, Reference Joubert1999). Valence electrons were described in terms of a plane-wave basis set.

Optimization result with the fixed unit cell was used as the starting geometry and the sources of bond and angle restraints in the Rietveld refinement (Rietveld, Reference Rietveld1967) for synchrotron powder XRD data. Atomic coordinates were taken from the PBE-PAW optimized model and refined with the Topas 5.0 software. Isotropic displacement parameters were constrained to be equal for all carbon atoms, all oxygen, and all nitrogen atoms. The positions of the hydrogen atoms were calculated geometrically and refined in the riding model with U iso(H) = 1.2U iso(X). The final R-values are listed in Table I along with the corresponding values of Rietveld refinement results. The Rietveld plot is given in Figure 2.

TABLE I. Crystal data and structure refinement for palbociclib.

Figure 2. The Rietveld plot for the refinement of palbociclib. The blue and red lines represent the observed data points and the calculated pattern, respectively. The difference curve is gray.

A. Computational methods

The plane wave calculations were carried out in the VASP 5.4.1 program package (Kresse and Hafner, Reference Kresse and Hafner1993, Reference Kresse and Hafner1994; Kresse and Furthmüller, Reference Kresse and Furthmüller1996a, Reference Kresse and Furthmüller1996b) The PBE method (Perdew et al., Reference Perdew, Kurth, Zupan and Blaha1999) and projected augmented waves (PAW) (Kresse and Joubert, Reference Kresse and Joubert1999; Kresse and Hafner, Reference Kresse and Hafner2000) were used. Valence electrons (2s and 2p for O, N, and C atoms; 1s for H) were described in terms of a plane-wave basis set. The kinetic energy cutoff for the wave functions was set to 800 eV. Automatic k-point sampling was used. The total energy and force convergence thresholds were set to 10−6 and 10−4 eV, respectively. The crystal structures from the powder X-ray diffraction experiment were used as the starting geometry for the calculations. The geometry optimizations were carried out with the lattice parameters fixed at their refined crystallographic values. The output files with the relaxed geometries were converted to a res-file using VESTA (Momma and Izumi, Reference Momma and Izumi2011).

III. RESULTS AND DISCUSSION

The asymmetric unit of palbociclib contains one molecule (Figure 3). The root-mean-square Cartesian displacement of the non-H atoms in the Rietveld-refined model and VASP-optimized structures is 0.070 Å (Figure 4); the maximum deviation of non-H atoms are 0.133 and 0.153 Å at O2 and C9 atoms of the acetyl group. Besides, positions of hydrogen atoms of methyl groups also differ. The atomic displacement is within the typical range for correct structures (van de Streek and Neumann, Reference van de Streek and Neumann2014). Almost all of the bond distances and bond angles in the experimental model fall within the normal ranges indicated by a Mercury/Mogul Geometry check (Macrae et al., Reference Macrae, Sovago, Cottrell, Galek, McCabe, Pidcock, Platings, Shields, Stevens, Towler and Wood2020). The C6–N1, C15–N3, and C12–C13 distances of 1.422, 1.379, and 1.432 Å are flagged as unusual; however, these correspond well with the distances from the VASP model (1.429, 1.375, and 1.426 Å).

Figure 3. Asymmetric unit of palbociclib, with the atom numbering.

Figure 4. Comparison of the Rietveld-refined (red) and VASP-optimized (blue) structures of palbociclib.

Piperazinyl realizes the chair conformation (Figure 3). The plane-to-plane twist angle between the pyridine and pyrido[2,3-d]pyrimidine is 16.7(1)°. The cyclopentyl ring is in the twist conformation with C4 and C5 shift from the C1–C2–C3 mean plane of 0.241(6) and −0.463(6) Å. Palbociclib conformations in free base and previously reported single-crystal salts and cocrystals are visualized in Figure 5. The pyridine and pyridopyrimidine heterocycles are nearly coplanar, while the positions of acetyl, cyclopentyl, and piperazinyl groups strongly differ in different solids. Nevertheless, the piperazinyl ring is always in the chair conformation, and the cyclopentyl ring demonstrates lability both through different conformations, and prominent thermal motion.

Figure 5. Palbociclib conformations in free base palbociclib (red), kaempferol palbociclib (orange, Zhou et al., Reference Zhou, Duan, Qin, Huang, Hou, Chen, Zhu, Xu, Jin and Zhuang2023), bis(palbociclib) oxalate dihydrate (green, Katiyar et al., Reference Katiyar, Ahamad, Dash, Tripathi, Arora and Thakur2021), palbociclib methanesulfonate monohydrate (blue, Allu et al., Reference Allu, An, Park and Kim2024), palbociclib benzenesulfonate hemihydrate (purple, Allu et al., Reference Allu, An, Park and Kim2024), and palbociclib ethanesulfonate (magenta, Allu et al., Reference Allu, An, Park and Kim2024) structures. H atoms are omitted for clarity.

Each molecule takes part in strong N–H⋯N-bonding. Parameters of these bonds for the theoretical model are listed in Table II. Neighboring molecules of palbociclib are connected to dimers through an inversion center by means of two N4–H4⋯N2 bonds supported by two C5–H5⋯N5 interactions. The dimers are further connected by N7–H7a⋯N7 hydrogen bonds into infinite layers parallel with (001) planes (Figure 6). Besides, the molecules are involved in weak C–H⋯O bonding which connects the layers into a 3D framework.

TABLE II. Hydrogen bonds (VASP 5.4.1) of palbociclib.

Figure 6. Fragment of N–H⋯N bonded layers in palbociclib. H-bonds are depicted with dotted lines.

Patent US10329290B2 publishes the characteristic peaks for palbociclib free base crystal form A at 2θ angles of 8.0° ± 0.2°, 10.1° ± 0.2°, 10.3° ± 0.2°, 11.5° ± 0.2° (for Cu Kα radiation). The crystal form B has the characteristic peaks at 2θ angles of 6.0° ± 0.2°, 10.9° ± 0.2°, 12.8° ± 0.2°, 16.4° ± 0.2°, and 19.8° ± 0.2° for Cu Kα radiation. The calculated pattern for our model for Cu Kα radiation comprises the characteristic peaks at 2θ = 5.02°, 7.98°, 10.02°, 10.24°, 11.52°, etc. (Supplementary Figure S1) which correspond to the anhydrous form A of palbociclib.

The volume per palbociclib molecule is equal to its molecular Voronoi polyhedron V VP = 554.7 Å3. The molecular Voronoi polyhedron is expected to be constant for a molecule in a different environment (Baburin and Blatov, Reference Baburin and Blatov2004; Prokaeva et al., Reference Prokaeva, Baburin and Serezhkin2009). Indeed, for palbociclib molecule in a cocrystal with kaempferol V VP obtained using ToposPro package (Blatov et al., Reference Blatov, Shevchenko and Proserpio2014) is equal to 560.3 Å3 (Zhou et al., Reference Zhou, Duan, Qin, Huang, Hou, Chen, Zhu, Xu, Jin and Zhuang2023). The V VP value of palbociclib cations in bis(palbociclib) oxalate dihydrate (565.0 Å3 (Katiyar et al., Reference Katiyar, Ahamad, Dash, Tripathi, Arora and Thakur2021)) and palbociclib ethanesulfonate (567.9 Å3 (Allu et al., Reference Allu, An, Park and Kim2024)) is also close to the value of free base palbociclib, while in palbociclib methanesulfonate monohydrate (580.2 Å3 (Allu et al., Reference Allu, An, Park and Kim2024)) and palbociclib benzenesulfonate hemihydrate (590.1 Å3 (Allu et al., Reference Allu, An, Park and Kim2024)), it is higher.

IV. DEPOSITED DATA

The powder pattern of the title compound from this synchrotron data set has been submitted to ICDD for inclusion in the Powder Diffraction File. The CIF files containing the results of the Rietveld refinement (including the raw data) and the DFT geometry optimization were deposited with the ICDD and the CSD (CCDC 2363921) The data can be requested at and www.ccdc.cam.ac.uk/structures, respectively.

SUPPLEMENTARY MATERIAL

The supplementary material for this article can be found at https://doi.org/10.1017/S0885715624000411.

ACKNOWLEDGEMENTS

This research was funded by the Russian Science Foundation, Grant No. 23-73-00027.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Footnotes

†

Deceased

References

REFERENCES

Allu, S., An, J.-H., Park, B. J., and Kim, W.-S.. 2024. “Improving Dissolution Rate and Solubility of Palbociclib Salts/Cocrystal for Anticancer Efficacy.” Journal of Molecular Structure 1305 (6): 137756. doi:10.1016/j.molstruc.2024.137756.CrossRefGoogle Scholar
Baburin, I. A., and Blatov, V. A.. 2004. “Sizes of Molecules in Organic Crystals: The Voronoi–Dirichlet Approach.” Acta Crystallographica Section B: Structural Science 60 (4): 447–52. doi:10.1107/S0108768104012698.CrossRefGoogle ScholarPubMed
Blatov, V. A., Shevchenko, A. P., and Proserpio, D. M.. 2014. “Applied Topological Analysis of Crystal Structures with the Program Package ToposPro.” Crystal Growth & Design 14 (7): 3576–86. doi:10.1021/cg500498k.CrossRefGoogle Scholar
Blöchl, P. E. 1994. “Projector Augmented-Wave Method.” Physical Review B 50 (24): 17953–79. doi:10.1103/PhysRevB.50.17953.CrossRefGoogle ScholarPubMed
“Bruker TOPAS 5 User Manual”. 2014. Karlsruhe, Germany: Bruker AXS GmbH.Google Scholar
Buikin, P. A., Vologzhanina, A. V., Novikov, R. A., and Korlyukov, A. A.. 2024a. “9-Ethyl-6,6-Dimethyl-8-[4-(Morpholin-4-Yl)Piperidin-1-Yl]-11-Oxo-6,11-Dihydro-5H-Benzo[b]Carbazole-3-Carbonitrile Hydrochloride.” Molbank 2024 (1): M1759. doi:10.3390/M1759.CrossRefGoogle Scholar
Buikin, P., Korlyukov, A., Kulikova, E., Novikov, R., and Vologzhanina, A.. 2024b. “Crystal Structure of Rilpivirine Hydrochloride, N6H19C22Cl.” Powder Diffraction 39 (3): 151–8. doi:10.1017/S0885715624000228.CrossRefGoogle Scholar
Coelho, A. A. 2003. “Indexing of Powder Diffraction Patterns by Iterative Use of Singular Value Decomposition.” Journal of Applied Crystallography 36 (1): 86–95. doi:10.1107/S0021889802019878.CrossRefGoogle Scholar
Fan, H., Guo, X., Huang, L., and Gu, H.. 2019. “Preparation Methods for Palbociclib Free Base Crystal Form A and Crystal Form B.” United States Patent US10329290B2. https://patents.google.com/patent/US10329290B2/en?oq=US10329290B2.Google Scholar
Fan, H., Guo, X., Huang, L., and Gu, H.. 2020. “Preparation Methods for Palbociclib Free Base Crystal Form A and Crystal Form B.” United States Patent US10766895B2. https://patents.google.com/patent/US10766895B2/en?oq=US10766895B2.Google Scholar
Finn, R. S., Dering, H., Conklin, D., Kalous, O., Cohen, D. J., Desai, A. J., Ginther, C., Atefi, M., Chen, I., Fowst, C., Los, G., and Slamon, D. J.. 2009. “PD 0332991, a Selective Cyclin D Kinase 4/6 Inhibitor, Preferentially Inhibits Proliferation of Luminal Estrogen Receptor-Positive Human Breast Cancer Cell Lines in Vitro.” Breast Cancer Research 11 (5): R77. doi:10.1186/bcr2419.CrossRefGoogle ScholarPubMed
Goloveshkin, A. S., Korlyukov, A. A., and Vologzhanina, A. V.. 2021. “Novel Polymorph of Favipiravir — An Antiviral Medication.” Pharmaceutics 13 (2): 139. doi:10.3390/pharmaceutics13020139.CrossRefGoogle ScholarPubMed
Goloveshkin, A. S., Kulikova, E. S., Novikov, R. A., Vologzhanina, A. V., and Korlyukov, A. A.. 2024. “Crystal Structure of Nilotinib Hydrochloride Monohydrate According to Powder X-Ray Diffraction Data.” Journal of Structural Chemistry 65 (3): 585–95. doi:10.1134/S0022476624030132.CrossRefGoogle Scholar
Ibrahim, F. M. L., Mullarney, M. P., Shanker, R. M., Spong, B. R., and Wang, J.. 2016. “Solid Dosage Forms of Palbociclib.” World Intellectual Property Organization Patent WO2016193860A1. https://patents.google.com/patent/WO2016193860A1/en?oq=WO2016193860A1Google Scholar
Joubert, D. 1999. “From Ultrasoft Pseudopotentials to the Projector Augmented-Wave Method.” Physical Review B - Condensed Matter and Materials Physics 59 (3): 1758–75. doi:10.1103/PhysRevB.59.1758.Google Scholar
Katiyar, D., Ahamad, S., Dash, S. G., Tripathi, S., Arora, A., and Thakur, T. S.. 2021. “Understanding the Guest Binding in the Cucurbit[7]Uril Inclusion Complexes of CDK4/6 Inhibitors, Palbociclib, and Ribociclib from a Combined Experimental and Computational Study.” Journal of Molecular Structure 1241 (10): 130637. doi:10.1016/j.molstruc.2021.130637.CrossRefGoogle Scholar
Kresse, G., and Furthmüller, J.. 1996a. “Efficiency of Ab-Initio Total Energy Calculations for Metals and Semiconductors Using a Plane-Wave Basis Set.” Computational Materials Science 6 (1): 15–50. doi:10.1016/0927-0256(96)00008-0.CrossRefGoogle Scholar
Kresse, G., and Furthmüller, J.. 1996b. “Efficient Iterative Schemes for Ab Initio Total-Energy Calculations Using a Plane-Wave Basis Set.” Physical Review B - Condensed Matter and Materials Physics 54 (16): 11169–86. doi:10.1103/PhysRevB.54.11169.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 1993. “Ab Initio Molecular Dynamics for Liquid Metals.” Physical Review B 47 (1): 558–61. doi:10.1103/PhysRevB.47.558.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 1994. “Ab Initio Molecular-Dynamics Simulation of the Liquid-Metal–Amorphous-Semiconductor Transition in Germanium.” Physical Review B 49 (20): 14251–69. doi:10.1103/PhysRevB.49.14251.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 2000. “First-Principles Study of the Adsorption of Atomic H on Ni (111), (100) and (110).” Surface Science 459 (3): 287–302. doi:10.1016/S0039-6028(00)00457-X.CrossRefGoogle Scholar
Kresse, G., and Joubert, D.. 1999. “From Ultrasoft Pseudopotentials to the Projector Augmented-Wave Method.” Physical Review B 59 (3): 1758–75. doi:10.1103/PhysRevB.59.1758.CrossRefGoogle Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M., and Wood, P. A.. 2020. “Mercury 4.0: From Visualization to Analysis, Design and Prediction.” Journal of Applied Crystallography 53 (1): 226–35. doi:10.1107/S1600576719014092.CrossRefGoogle ScholarPubMed
Momma, K., and Izumi, F.. 2011. “VESTA 3 for Three-Dimensional Visualization of Crystal, Volumetric and Morphology Data.” Journal of Applied Crystallography 44 (6): 1272–76. doi:10.1107/S0021889811038970.CrossRefGoogle Scholar
Morris, M. C., McMurdie, H. F., Evans, E. H., Paretzkin, B., Parker, H. S., Pyrros, H. S., and Hubbard, C. R.. 1984. “Standard X-Ray Diffraction Powder Patterns: Section 20 - Data for 71 Substances.” Gaithersburg, MD: National Institute of Standards and Technology. doi:10.6028/NBS.MONO.25-20.CrossRefGoogle Scholar
O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., and Hutchison, G. R.. 2011. “Open Babel: An Open Chemical Toolbox.” Journal of Cheminformatics 3 (1): 33. doi:10.1186/1758-2946-3-33.CrossRefGoogle ScholarPubMed
Perdew, J. P., Kurth, S., Zupan, A., and Blaha, P.. 1999. “Accurate Density Functional with Correct Formal Properties: A Step Beyond the Generalized Gradient Approximation.” Physical Review Letters 82 (12): 2544–47. doi:10.1103/PhysRevLett.82.2544.CrossRefGoogle Scholar
Prokaeva, M. A., Baburin, I. A., and Serezhkin, V. N.. 2009. “On Methods to Determine the Surface Areas of Molecules.” Journal of Structural Chemistry 50 (5): 867–72. doi:10.1007/s10947-009-0129-5.CrossRefGoogle Scholar
Rietveld, H. M. 1967. “Line Profiles of Neutron Powder-Diffraction Peaks for Structure Refinement.” Acta Crystallographica 22 (1): 151–52. doi:10.1107/S0365110X67000234.CrossRefGoogle Scholar
Rocca, A., Farolfi, A., Bravaccini, S., Schirone, A., and Amadori, D.. 2014. “Palbociclib (PD 0332991): Targeting the Cell Cycle Machinery in Breast Cancer.” Expert Opinion on Pharmacotherapy 15 (3): 407–20. doi:10.1517/14656566.2014.870555.CrossRefGoogle ScholarPubMed
Svetogorov, R. D. 2018. Dionis – Diffraction Open Integration Software. Moscow: National Research Center, Kurchatov Institute.Google Scholar
Svetogorov, R. D., Dorovatovskii, P. V., and Lazarenko, V. A.. 2020. “Belok/XSA Diffraction Beamline for Studying Crystalline Samples at Kurchatov Synchrotron Radiation Source.” Crystal Research and Technology 55 (5): 1900184. doi:10.1002/crat.201900184.CrossRefGoogle Scholar
van de Streek, J., and Neumann, M. A.. 2014. “Validation of Molecular Crystal Structures from Powder Diffraction Data with Dispersion-Corrected Density Functional Theory (DFT-D).” Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials 70 (6): 1020–32. doi:10.1107/S2052520614022902.CrossRefGoogle ScholarPubMed
Zhou, H., Duan, C., Qin, H., Huang, C., Hou, J., Chen, Y., Zhu, J., Xu, C., Jin, J., and Zhuang, T.. 2023. “Synthesis and Structural Characterization of a Novel Palbociclib-Kaempferol Cocrystal with Improved Tabletability and Synergistic Antitumor Activity.” Journal of Molecular Structure 1281 (6): 135101. doi:10.1016/j.molstruc.2023.135101.CrossRefGoogle Scholar
Figure 0

Figure 1. The molecular structure of palbociclib.

Figure 1

TABLE I. Crystal data and structure refinement for palbociclib.

Figure 2

Figure 2. The Rietveld plot for the refinement of palbociclib. The blue and red lines represent the observed data points and the calculated pattern, respectively. The difference curve is gray.

Figure 3

Figure 3. Asymmetric unit of palbociclib, with the atom numbering.

Figure 4

Figure 4. Comparison of the Rietveld-refined (red) and VASP-optimized (blue) structures of palbociclib.

Figure 5

Figure 5. Palbociclib conformations in free base palbociclib (red), kaempferol palbociclib (orange, Zhou et al., 2023), bis(palbociclib) oxalate dihydrate (green, Katiyar et al., 2021), palbociclib methanesulfonate monohydrate (blue, Allu et al., 2024), palbociclib benzenesulfonate hemihydrate (purple, Allu et al., 2024), and palbociclib ethanesulfonate (magenta, Allu et al., 2024) structures. H atoms are omitted for clarity.

Figure 6

TABLE II. Hydrogen bonds (VASP 5.4.1) of palbociclib.

Figure 7

Figure 6. Fragment of N–H⋯N bonded layers in palbociclib. H-bonds are depicted with dotted lines.

Supplementary material: File

Buikin et al. supplementary material

Buikin et al. supplementary material
Download Buikin et al. supplementary material(File)
File 55.9 KB