High-Pressure Crystallization and Structural Transformations in

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High-pressure crystallization and structural transformations in compressed R,S-ibuprofen Kinga Ostrowska, Magdalena Kropidlowska, and Andrzej Katrusiak Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/cg5018888 • Publication Date (Web): 10 Feb 2015 Downloaded from http://pubs.acs.org on February 18, 2015

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Crystal Growth & Design

High-pressure crystallization and structural transformations in compressed R,S-ibuprofen Kinga Ostrowska, Magdalena Kropidłowska and Andrzej Katrusiak* Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland KEYWORDS.

High-pressure;

crystallization;

crystal

compression;

hydrogen

bond;

intermolecular interactions.

ABSTRACT

R,S-Ibuprofen

dissolved in chiral and achiral solvents recrystallizes at varied

pressure and temperature in the same racemic form I of monoclinic space group P21/c. At 4.0 GPa the crystal is compressed to 78% of its ambient-pressure volume. The main structural transformation is the compression of intermolecular van der Waals contacts, increasing the effects of intermolecular interactions in the crystal environment, which results in the more skew position of OH···O bonded carboxyl groups and more stabile H-atoms in the bistable H-bonds. Consequently, the H-atoms remain ordered in all pressure range investigated, despite the compression of the H-bonds by over 0.1 Å at 4 GPa. The crystal compression and thermal expansion obey the reverse relationship rule of temperature and pressure effects, however the compression is considerably non-linear due to the strong reduction of voids volume up about 0.8 GPa.

INTRODUCTION

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Several active pharmaceutical ingredients (APIs) have been recently subjected to structural studies at high pressure, aimed at obtaining new crystalline forms advantageous for their applications.1-6 (R,S)-Ibuprofen (Figure 1) is an important non-steroidal anti-inflammatory feverreducing and pain-relieving API.7 The commercially available R,S-ibuprofen is monoclinic, space group P21/c (phase I).8-9 The dextrorotatory enantiomer, S-ibuprofen is more active and hence desired for pharmaceutical applications.10 Therefore methods of resolving the ibuprofen enantiomers are intensely sought.11-13 Recently, a new crystalline phase II of the racemate was detected by differential scanning calorimetry (DSC)14 and its structure (of space group P21/c, like form I) was determined by X-ray powder diffraction (XRPD).15-16 The structure of S-ibuprofen was determined, too. It is monoclinic, space group P21.17 In this study we intended to crystallize racemic ibuprofen at high pressure from different achiral and chiral solutions. We were also interested in the conformation of this flexible molecule (Figure 1), stability of ambient-pressure phase I and possible high-pressure phases of ibuprofen. Ibuprofen is a typical carboxylic acid with molecules linked by double OH···O bridges into R 22 (8) dimers.18 The acidic protons in R,S-ibuprofen

I are ordered, differently than in benzoic acid at the same thermodynamic

conditions.19 It was shown that the acidic H-atoms behavior depends on the effects of crystal environment of the carboxyl gropus.20 Presently we intended to investigate the effect of pressure on the ordered carboxyl H-atoms in R,S-ibuprofen I.


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Figure 1. The molecule of ibuprofen I with its four most soft torsion angles, except those of the methyl rotors. EXPERIMENTAL (R,S)-Ibuprofen has been investigated at low temperature and high pressure. The single crystal was mounted on diffractometers Oxford Diffraction SuperNova using CuKα radiation and Xcalibur, equipped with an EOS-CCD detector, an X-rays MoKα microsource and a Cryosystem low-temperature attachment. Single-crystal diffraction data were collected at 100, 150, 200, 250, 296 K/0.01 MPa. We recrystallized (R,S)-ibuprofen from different chiral solvents in isothermal and isochoric conditions. The high-pressure study was performed on the single crystals grown in a MerrillBassett21 diamond-anvil cell (DAC) from chiral solvents: ethyl (S)-lactate, methyl (S)-lactate, (S)limonene; also co-crystallizations of ibuprofen with chiral compounds were attempted of (R,S)-ibuprofen:(D)-glucose:ethanol (1:1:1 vol.), (R,S)-ibuprofen:(S)-mandelic acid:ethanol (1:1:1 vol.), (R,S)-ibuprofen:(D)-tartaric acid:water (2:1:5 vol.) solutions. For each of these solvents


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several crystallizations were tried in the pressure range between 0.1 and 1.15 GPa and temperature up to 553 K (cf. Table S1 in Supporting Information). All these crystallizations yielded the racemic polymorph I only. In the high-pressure conditions the crystals grew very slowly and only low-quality small crystals of different morphologies were obtained (Figure 2). Because of the small size of the crystals grown in this way their form could be identified only for the samples recovered from the DAC. The attempts to co-crystallize R,S-ibuprofen with

D-

glucose, S-mandelic acid and D-tartaric acid enantiomers (1:1 vol.) resulted in these compounds crystallized (S7-S9 in Supporting Information). We have determined the effect of pressure on the R,S-ibuprofen

form I for a single crystal, 0.43 x 0.10 x 0.05 mm in size, mounted in the DAC

(Figure 3). The gasket was made of 0.3 mm thick inconel foil and the initial diameter of the spark-eroded hole was 0.5 mm; glycerin was used as hydrostatic medium. Pressure was calibrated by the ruby-fluorescence method22-24 with a Photon Control spectrometer, with a precision of 0.02 GPa. Single-crystal diffraction data were collected at 0.23, 0.60, 0.80, 0.88, 1.70, 1.89, 2.32, 2.65, 3.46 and 4.00 GPa/296 K, on diffractometers KUMA KM4-CCD, with graphite-monochromated MoKα radiation, and Xcalibur, equipped with an EOS-CCD detector with an X-rays AgKα microsource. The centering of the DAC was performed by the gasketshadowing method.25 The hydrostatic limit of 3 GPa in glycerin have been exceeded for the highest pressure points; it appeared that the non-hydrostatic pressure did not affect the unit-cell compression (Figure 4), however the structural data clearly diverted at 4.0 GPa (Figure 5). We have included these results for illustrating the possible effects of non-hydrostatic pressure.


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Figure 2. Crystallization of R,S-ibuprofen grown of the methyl S-lactate in isochoric conditions: (a) a low-quality, according to X-ray diffraction, multiple-twin of R,S-ibuprofen crystal in the DAC at 0.48 GPa; (b) a seed obtained of the same sample dissolved at 393 K and cooled slowly to 296 K, when pressure stabilized to 0.52 GPa; and (c) an R,S-ibuprofen I crystal grown in another experiment from the methyl S-lactate solution at 0.53 GPa/296 K. The ruby chips for pressure calibration lie by the top edge of the gasket.

Figure 3. The crystal sample of ibuprofen I from glycerine solution at: (a) 2.65 GPa, (b) 3.46 GPa, (c) 4.00 GPa; all at 296 K. The ruby chip for pressure calibration initially lied at the left edge of the chamber (a, b) and then moved to the right side (c). CrysAlis software26 was used for the data collection and the preliminary reduction of the data. After correcting the intensities for the effects of the DAC absorption, the sample shadowing by the gasket and the sample absorption,26 the diamond reflections were eliminated. The unit-cell dimensions and space-group symmetry were consistent with the ambient-pressure structure, which was used as a starting model for full-matrix least-squares refinement.27 Anisotropic temperature factors were generally applied for non-hydrogen atoms. H-Atoms were located from molecular geometry, their Uiso’s equal to 1.2 times Ueq of their carrier atoms. The experimental details are given in Table S2 of the Supporting Information. Structural drawings have been prepared using program Mercury 3.3.28 The structural information have been deposited in the CIF form in the Cambridge Crystallographic Database and is available in the CIF format free of


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charge

on

request

form

Cambridge

Crystallographic

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Database

Centre

or

at

www.ccdc.cam.ac.uk/cif.

DISCUSSION The compressed crystals of R,S-ibuprofen I retain the ambient-pressure monoclinic symmetry of space group P21/c to 4 GPa at least. The thermal expansion of ibuprofen I between 100 and 300 K and the crystal compression up to 4 GPa are monotonic (Figure 4). The molecular conformation is hardly affected by temperature and changes at most by 8° for torsion angles τ3 and τ4 under pressure (Figure 5).


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Figure 4. (a) Unit-cell dimensions of R,S-ibuprofen I, related to the values at 296 K/0.1 MPa, as a function of temperature (top) and pressure (bottom). The volume of (R,S)-ibuprofen form II14-16 (diamond) and S-ibuprofen17 (triangle) are indicated in the top plot. (b) Temperature (open circles) and pressure (full circles) dependence of the β angle in ibuprofen I. The magnitudes of unit-cell parameters have been plotted in Figures S1 and S2 in the Supporting Information.


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Figure 5. Changes in torsion angles τ1 (red, cf. Figure 1), τ2 (blue), τ3 (green) and τ4 (black) in R,S-ibuprofen

I as a function of (a) pressure and (b) temperature, all related to the angles at

0.1 MPa/296 K. Monotonic transformations of τ values have been assumed and the value at 4 GPa have been excluded from fitting the curve (see Experimental). The values of torsion angles are plotted in Figure S6 in the Supporting Information. It was shown recently that the H-sites in carboxylic acids are coupled to the distortions from the mirror symmetry between the H-bonded carboxyl groups, in

R,S-ibuprofen

labelled

C9O2O1H1 and C9iO2iO1iH1i (symmetry code i=1-x,-y,1-z), measured quantitatively by the skewness parameter s equal to s = [η(C9O2O1i) – η (C9O1O2i) + η (C9iO2iO1) – η (C9iO1iO2)]/2 where η are Donohue angles C-O···Oi. In principle, the positive s values (larger than 4°) stabilize the ordered H sites at O1and O1i, while the s values around 0° are characteristic for


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disordered H atoms; negative s values are highly unlikely.20 This coupling between the H-sites and s-values is due to the different hybridization of the O atoms and its geometrical consequences.20,29-30

Figure 6. The crystal packing of OH···O bonded dimers in R,S-ibuprofen I. The OH···O bonds are indicated by cyan dotted lines and shortest CH···O contacts by red dotted lines.


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Figure 7. Pressure dependence of H-bonds and shortest intermolecular contacts: (a) distances H···O; (b) O···O and C···O. The symmetry codes: (i)=1-x,-y,1-z; (ii)=1-x,1-y,1-z; (iii)=x,0.5-y,0.5+z. The dashed lines indicate the sums of van der Waals radii (vdW) of atoms H, O and C, as indicated by the subscripts. The systematic changes in Donohue angles of the OH···O bonds in R,S-ibuprofen I correlate with intermolecular contacts around the carboxyl group of the dimer (Figures 6 and 7). The shortest contacts between the dimers in the crystal structure are these involving the carboxyl oxygen O2: O2···H2Aii of 2.63 Å, O2···H3Aii of 2.84 Å and O2···H8Aiii of 2.97 Å. The shortest intermolecular contact involving O1 is O1···H8Ciii of 3.10 Å, which is about 0.5 Å longer than O2···H2Aii. Thus it is apparent that the skewness of the carboxylic junction in the dimers adjusts to the crystal environment: smaller skewness values would result in even shorter O2···H2Aii and


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longer O1···H8Ciii distances. The crystal-structure compression of

R,S-ibuprofen

I further

supports the role of the crystal environment for the skewness of the carboxyl OH···O junction: at 4.0 GPa the shortest contact O2···H2Aii is compressed by 0.3 Å, and 0.3 Å less than the shortest contact of O1···H8Ciii (Figure 7). This difference in compressed contacts of carboxyl O-atoms is partly ‘absorbed’ by the deformation of the carboxyl junction increasing its skewness by ∆s≈sin1

(0.3 Å/2.65 Å)≈6.5°. This value perfectly agrees with the pressure dependence of skewness

parameter s (Figure 8).

Figure 8. Skewness parameter s (Equation 1) plotted as a function of pressure (full circles) and temperature (open circles) for the OH···O bonded carboxyl groups in R,S-ibuprofen I. The inset shows the dimer with all but the acidic H-atoms omitted for clarity. Figure 8 also includes the s values in R,S-ibuprofen II14-16 (diamond) and S-ibuprofen17 (triangle). High pressure affects the H-ordering in carboxylic acids by (i) increasing intermolecular interactions involving the carboxyl oxygen atoms, which either increases or reduces skewness s; and by (ii) compressing the O···Oi distances, which reduces the potential-energy barrier between the H-sites and facilitates the H-disordering. In benzoic acid at normal conditions the skewness s


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is of 0.4° and the H-atoms are 50:50 disordered. Pressure initially increases s (to 2° at 1 GPa) and the H-ordering increases. The H-ordering is counteracted by the O···O compression (from 2.7 Å at 0.1 MPa to 2.5 Å at 2 GPa) and at 2 GPa the H-atoms are disordered again at 50:50 rate and the skewness s is reduced to 0.4°. In R,S-ibuprofen I the ambient-pressure skewness s of 18° hardly depends on temperature (Figure 8) but pressure increases s to 25.5° at 4 GPa. Thus pressure further stabilizes the H-sites, despite the compression of the O···O distances from 2.664(2) at 0.1 MPa to 2.55(1) Å at 4 GPa (Figure 6). Accordingly, the C-O1 bond remains longer by about 0.08 Å than bond C=O2 through all the pressure range (Figure 9). In R,Sibuprofen II, skewness s is close to 0º, which testifies that the carboxyl H-atoms are disordered in that polymorph and that the H-ordering depends on the crystal structure. It is characteristic that despite ordered H-atoms sites the C9=O2 bond becomes gradually longer (Figure 9a), which results from the compressed O2···H9i distances.31


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Figure 9. Pressure (a) and temperature (b) dependence of C-O1 and C=O2 bond distances in R,S-ibuprofen

I.

The structural changes in the compressed crystal are strongest for the intermolecular voids, reduced by 80% between 0.1 MPa and 3.5 GPa; in this pressure range the crystal-volume is compressed by 20%. Unlike the thermal expansion, the crystal compression is clearly non-linear, which can be mainly associated with the very non-linear compression of the voids particularly strong up to about 0.8 GPa (compare Figures 4, 10 and S3).

Figure 10. Relative changes of voids volume in the (a) compressed and (b) cooled crystal of R,S-ibuprofen

I. The voids volume was calculated by program Mercury28 for the probing-sphere

radius of 0.4 Å and 0.3 Å steps. The lines are for guiding the eye only. CONCLUSIONS Pressure primarily reduces the voids volume and increase intermolecular interactions in R,Sibuprofen I, but does not destabilize this structure. Most reduced are the van der Waals contacts,


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the shortest of CH···O bonds are compressed by about 0.3 Å at 4 GPa. Despite the compression of the OH···O distance by 0.1 Å which considerably reduced the potential energy barrier in the bistable hydrogen bond, the carboxyl H-atoms remained stable at 4 GPa. The ordered H-atoms have been attributed to the effect of crystal environment, further increased by pressure, when compressed contacts push the H-bonded carboxyl groups toward less symmetric positions. This effect has been measured quantitatively as a pressure dependence of skewness parameter s. The molecular conformation slightly adjusts in the compressed environment. All structural changes have a stabilizing effect for the R,S-ibuprofen I phase, which was also obtained from highpressure crystallizations of the aqueous, methanol, ethanol, S-limonene, ethyl S-lactate and methyl S-lactate solutions. These results of high-pressure crystallizations and structural changes determined at low temperature and high pressure consistently indicate that solvation or recrystallization of R,S-ibuprofen into a new phase at high pressure is unlikely. Although these results cannot rule out possibility of other forms of ibuprofen obtained at high pressure, particularly when a suitable solvent were found, they may be an indication that low-pressure crystallizations may be more likely to yield new forms of the racemate of this compound. It can be noted that it was suggested that high pressure could be used for resolving the racemate into enantiomers, if the former are less dense than the latter.32 However the density of R,S-ibuprofen I at normal conditions, of 1.117 gcm-3, is larger than that of S-ibuprofen, of 1.100 gcm-3, so the pressure driven resolution of the racemate into enantiomers is highly unlikely. The enantiomers would have to be much stronger compressed monotonically or undergo strong 1st-order phase transitions,33 to become more dense than the racemate, which was the primary condition considered by Collet and Vigne-Maeder 34 for such a resolution.


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ASSOCIATED CONTENT The Supporting Information includes the plots of the structural dimensions as a function of pressure and temperature, the photographs of methyl S-lactate, glucose, mandelic acid and tartaric acid obtained of their mixtures with R,S-ibuprofen at high-pressure conditions and the tables with X-ray diffraction experimental details and crystallographic information. Deposits CCDC 1041369-1041383 contain supplementary crystallographic data for high-pressure and low-temperature measurements for R,S-ibuprofen form I. These data can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/data_request/cif and from http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. ACKNOWLEDGMENT The study was supported by the TEAM Programme of the Foundation for Polish Science, TEAM 2009-4/6 REFERENCES [1] Shakhtshneider, T. P.; Boldyreva, E. V.; Vasilchenko, M. A.; Ahsbahs, H.; Uchtmann, H. Anisotropy of crystal structure distortion in organic molecular crystals of drugs induced by hydrostatic compression. J. Struct. Chem. 1999, 40, 892-898. [2] Boldyreva, E. V.; Shakhtshneider, T. P.; Vasilchenko, M. A.; Ahsbahsc H.; Uchtmann, H. Anisotropic crystal structure distortion of the monoclinic polymorph of acetaminophen at high hydrostatic pressures. Acta Cryst. Sect. B 2000, 56, 299-309.


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[3] Boldyreva, E. V.; Shakhtshneider, T. P.; Ahsbahs, H.; Sowa, H.; Uchtmann, H. Effect of high pressure on the polymorphs of paracetamol. J. Therm. Anal. Calorim. 2002, 68, 437-452. [4] Fabbiani, F. P. A.; Allan, D. R.; Dawson, A.; David, W. I. F.; McGregor, P. A.; Oswald, I. D. H.; Parsons, S.; Pulham, C. R. Pressure-induced formation of a solvate of paracetamol. ChemComm. 2003, 9, 3004-3005. [5] Fabbiani, F. P. A.; Pulham, C. R. High-pressure studies of pharmaceutical compounds and energetic materials. Chem. Soc. Rev. 2006, 35, 932-942. [6] Fabbiani, F. P. A.; Allan, D. R.; David, W. I. F.; Davidson, A. J.; Lennie, A. R.; Parsons, S.; Pulham, C. R.; Warren, J. E. High-pressure studies of pharmaceuticals: An exploration of the behavior of piracetam. Cryst. Growth Des. 2007, 7, 1115-1124. [7] Van Esch, A.; Van Steensel-Moll, H. A.; Steyerberg, E. W.; Offringa, M.; Habbema, J. D.; Derksen-Lubsen, G. Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures. Arch. Pediatr. Adolesc. Med. 1995, 149, 632–637. [8] McConnell, J. F. The 2-(4-isobutylphenyl) propionic acid. Ibuprofen or prufen. Cryst. Struct. Commun. 1974, 3, 73–75. [9] Shankland, N.; Wilson, C. C.; Florence, A. J.; Cox, P. J. Refinement of Ibuprofen at 100K by Single-Crystal Pulsed Neutron Diffraction. Acta Cryst. Sect. C 1997, 53, 951–954. [10] Adams, S. S.; Bresloff, P.; Manson, C. G. Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of ibuprofen. J. Pharm. Pharmacol. 1976, 28, 256–257.


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[11] McCullagh, J. V. The Resolution of Ibuprofen, 2-(4'-Isobutylphenyl)propionic Acid. J. Chem. Educ. 2008, 85, 941-943. [12] Molnár, P.; Bombicz, P.; Varga, C.; Bereczki, L.; Székely, E.; Pokol, G.; Fogassy, E.; Simándi, B. Influence of benzylamine on the resolution of ibuprofen with (+)-(R)phenylethylamine via supercritical fluid extraction. Chirality 2009, 21, 628-636. [13] Lee, T.; Chen, Y. H.; Wang, Y. W. Effects of Homochiral Molecules of (S)-(+)-Ibuprofen and (S)-(−)-Sodium Ibuprofen Dihydrate on the Crystallization Kinetics of Racemic (R,S)-(±)Sodium Ibuprofen Dihydrate. Cryst. Growth Des. 2008, 8, 415–426. [14] Dudognon, E.; Dane`de, F.; Descamps, M.; Correia, N. T. Evidence for a New Crystalline Phase of Racemic Ibuprofen. Pharm. Res. 2008, 25, 2853-2858. [15] Derollez, P.; Dudognon, E.; Affouard, F.; Dane`de, F.; Correiab, N. T.; Descampsa, M. Ab initio structure determination of phase II of racemic ibuprofen by X-ray powder diffraction. Acta Cryst. Sect. B 2010, 66, 76–80. [16] Williams, P.A.; Hughes, C. E.; Harris, K. D. M. New Insights into the Preparation of the Low-Melting Polymorph of Racemic Ibuprofen. Cryst. Growth Des. 2012, 12, 5839–5845. [17] Freer, A. A.; Bunyan, J. M.; Shankland, N.; Sheen, D. B. Structure of (S)-(+)-ibuprofen. Acta Cryst. Sect. C 1993, 49, 1378–1380. [18] Etter, M. C.; MacDonald, J. C.; Bernstein, J. Graph-Set Analysis of Hydrogen-Bond Patterns in Organic Crystals. Acta Cryst. Sect. B 1990, 46, 256-262. [19] Cai, W.; Katrusiak, A. Pressure effects on H-ordering in hydrogen bonds and interactions in benzoic acid. CrystEngComm. 2012, 14, 4420-4424.


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[20] Ratajczak-Sitarz, M.; Katrusiak, A. Coupling of molecular orientation with the hydrogenbond dimensions and H-sites in carboxylic acids. J. Mol. Struct. 2011, 995, 29-34. [21] Merrill, L.; Bassett, W. A. Miniature diamond anvil cell for single crystal x-ray diffraction studies. Rev. Sci. Instrum. 1975, 45, 290-294. [22] Barnett, J. D.; Block, S.; Piermarini, G. J. An optical fluorescence system for quantitative pressure measurement in the diamond-anvil cell. Rev. Sci. Instrum. 1973, 44, 1-9. [23] Piermarini, G. J.; Block, S.; Barnett J. D.; Forman, R. A. Calibration of the Pressure Dependence of the R1 Ruby Fluorescence Line to 195 kbar. J. Appl. Phys. 1975, 46, 2774-2780. [24] Mao, H. K.; Xu, J.; Bell, P. M. Calibration of the ruby pressure gauge to 800 kbar under quasi-hydrostatic conditions. J. Geophys. Res.Sect. B 1986, 91, 4673−4676. [25] Budzianowski, A.; Katrusiak, A. High-Pressure Crystallographic Experiments with a CCD Detector. High-Pressure Crystallography; Katrusiak, A., McMillan, P., Eds.; Kluwer: Dordrecht, 2004., pp. 101–112. [26] CrysAlisCCD, CrysAlisRed; Oxford Diffraction (2006); Oxford Diffraction Ltd, Abingdon, England. [27] Sheldrick G. M. A short history of SHELX. Acta Cryst. Sect. A 2008, 64, 112–122. [28] Macrae, C. F.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. Mercury: visualization and analysis of crystal structures. J. Appl. Crystallogr. 2006, 39, 453−457.


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[29] Gajda, R.; Katrusiak, A.; Crassous, J. Pressure-controlled aggregation incarboxylic acids. A case study on the polymorphism of bromochlorofluoroacetic acid. CrystEngComm. 2009, 11, 2668-2676. [30] Katrusiak, A. Stereochemistry and transformation of -OH-O= hydrogen bonds. I. Polymorphism and phase transition of 1,3-cyclohexanedione crystals. J. Mol. Struct. 1992, 269, 329–354. [31] Katrusiak, A. High-Pressure X-ray Diffraction Studies on Organic Crystals. Cryst. Res. Technol. 1991, 26, 523-531. [32] Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates and Resolutions, Krieger Publishing Company: Malabar, FL, 1981, pp. 28-30, 144, 203-207. [33] Marciniak, J.; Andrzejewski, M.; Cai, W.; Katrusiak, A. Wallach's Rule Enforced by Pressure in Mandelic Acid. J. Phys. Chem. C. 2014, 118, 4309-4313. [34] Collet, A.; Vigne-Maeder, F. Sur l’augmentation de la fréquence des dédoublements spontanés par cristallisation des racemiques sous haute pression. New J. Chem. 1995, 19, 877879.


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For Table of Contents Use Only High-pressure crystallization and structural transformations in compressed R,S-ibuprofen Kinga Ostrowska, Magdalena Kropidłowska and Andrzej Katrusiak*

Polymorph I of R,S-ibuprofen is stable up to 4 GPa at least. Intermolecular voids are efficiently eliminated by pressure below 0.8 GPa, which results in strongly non-linear compression of the crystal. Despite squeezed OH···O bonds, the acidic H-atoms remain ordered due to the skew arrangement of the carboxyl groups supported by the crystal environment.


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High-Pressure Crystallization and Structural Transformations in

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