A Rare Case of Polymorphism in a Three-Component Co-Crystal

Communication pubs.acs.org/crystal

A Rare Case of Polymorphism in a Three-Component Co-Crystal System, with Each Polymorph Having Ten Independent Molecules in the Asymmetric Unit Yuncheng Yan, Colan E. Hughes, Benson M. Kariuki, and Kenneth D. M. Harris* School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, Wales, U.K. S Supporting Information *

ABSTRACT: We report polymorphism in a co-crystal system comprising trimesic acid (benzene-1,3,5-tricarboxylic acid, TMA), tert-butylamine (TBA), and methanol with stoichiometry (TMA)2(TBA)5(methanol)3. The crystal structure of each polymorph (determined from single-crystal X-ray diffraction) is shown to have 10 independent molecules in the asymmetric unit. In each polymorph, all five TBA molecules in the asymmetric unit exist as protonated cations, whereas, of the two TMA molecules in the asymmetric unit, one exists as the doubly deprotonated anion and the other exists as the triply deprotonated anion. In each case, the structure is based on an extensively hydrogen-bonded two-dimensional network involving the −N+H3 groups of TBA cations, the −CO2− and −CO2H groups of TMA anions, and the OH groups of methanol molecules. Although the two polymorphs share some structural features in common, there are nevertheless significant differences in several aspects, including differences in some of the hydrogen-bonding motifs. Among polymorphic systems reported previously, there are very few examples for which two polymorphs have 10 or more independent molecules in the asymmetric unit and very few examples of co-crystals comprising three or more distinct organic molecules. From both of these perspectives, the example of polymorphism reported here can be considered very rare.

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more distinct organic molecules (hence excluding hydrate structures) have been reported.5 In the present paper, we focus specifically on co-crystals formed between trimesic acid (benzene-1,3,5-tricarboxylic acid, TMA) and tert-butylamine (TBA). For this family of materials, a range of co-crystals with different ratios of the components may be anticipated, as TMA can give three different anions, depending on the degree of deprotonation.6,7 For clarity of notation, we use the abbreviations TBA and TMA to refer in general to tert-butylamine and trimesic acid respectively, without reference to the degree of protonation/deprotonation. To indicate explicitly the degree of protonation/deprotonation, we use tma3− to represent the fully deprotonated benzene1,3,5-tricarboxylate anion and tba to represent the neutral tertbutylamine molecule. Thus, the protonated TBA molecule is represented as Htba+, the neutral TMA molecule is represented as H3tma, and the three anions that correspond to different degrees of deprotonation of TMA are represented as H2tma−, Htma2−, and tma3−. For the case in which the neutral molecules are not present, the general formula for co-crystals containing TMA and TBA is as follows: (Htba+)x+2y+3z(H2tma−)x(Htma2−)y(tma3−)z. Furthermore, the formation of three-component co-crystals containing TMA,

any organic molecules can exist in several different forms in the solid state, such as polymorphs, co-crystals, hydrates, or solvates. Different crystalline forms of a given molecule can have significantly different solid-state properties, leading to contrasting performance in materials applications, and it is therefore important from both fundamental and applied (e.g., industrial) perspectives to understand the diversity of crystalline forms available to a given molecule. The term polymorphism1 refers to the situation in which two (or more) crystalline phases have identical chemical composition (as defined in the context of the Gibbs’ Phase Rule) but different crystal structures. It follows from this definition that a pair of two-component co-crystal materials with identical composition AxBy but different crystal structures are correctly classified as polymorphs. We note that, throughout this paper, the term co-crystal is used in its broadest sense2 to describe a crystal that contains two or more distinct types of molecule irrespective of whether these molecules are neutral, cationic, or anionic and irrespective of whether one of the molecules was the solvent used in the crystallization experiment. In the field of co-crystal materials, the existence of different solid forms containing the same components in different ratios is a relatively common occurrence. However, examples of multicomponent co-crystals (i.e., containing three or more different types of molecule) that exhibit polymorphism are very uncommon. According to the Cambridge Structural Database3,4 (CSD), only five polymorphic systems comprising three or © 2012 American Chemical Society

Received: November 1, 2012 Revised: December 4, 2012 Published: December 5, 2012 27

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TBA, and other types of molecule with hydrogen-bonding capability may also be anticipated. In this paper, we focus on the structural chemistry of an example of this type, specifically the system with composition (TMA)2(TBA)5(methanol)3, which represents both a rare case of polymorphism in a three-component co-crystal system and a rare case of polymorphs that both have a very high number (in this case 10) of independent molecules in the asymmetric unit. Single-crystal X-ray diffraction data were recorded at 150 K on a Nonius Kappa CCD diffractometer equipped with a molybdenum tube source (λ = 0.71073 Å). The crystal structures were solved (by direct methods) and refined using SHELX.8 Refinement of non-hydrogen atoms was carried out using anisotropic displacement parameters. All hydrogen atoms were located in difference Fourier maps and were added to the structural model according to idealized geometries. Refinement of hydrogen atoms was carried out using a riding model, with isotropic displacement parameter equal to 1.2 or 1.5 times the equivalent isotropic displacement parameter of the atom to which the hydrogen atom is bonded. Powder X-ray diffraction data were recorded on a Bruker D8 instrument (Cu Kα1; Ge monochromated; transmission geometry). Differential scanning calorimetry (DSC) data were measured on a TA Instruments Q100 using sealed aluminum pans and cooling rates between 1 and 20 °C min−1. The two polymorphs (denoted forms I and II) of (TMA)2(TBA)5(methanol)3 discovered in this work were prepared by vapor diffusion of antisolvent into a solution of TMA and TBA in methanol. Form I is obtained using acetone as antisolvent, and form II is obtained using ethanol as antisolvent. The same phases are obtained in crystallization experiments involving solutions with TBA/TMA molar ratios in the range 2−2.5. Our crystallization procedure to produce form II yielded monophasic samples, whereas our procedure to produce form I was frequently found to yield the concomitant formation of small amounts of form II. The structural properties9,10 of the two polymorphs of (TMA)2(TBA)5(methanol)3 have been determined from single-crystal X-ray diffraction data, and the crystal structures of forms I and II are shown in Figures 1 and 2, respectively. Following structure determination, simulation of the powder Xray diffraction pattern corresponding to each crystal structure confirmed that the crystal structures are representative of the experimental powder X-ray diffraction patterns of the bulk polycrystalline samples obtained in the crystallization experiments (in the case of form I, considering the experimental powder X-ray diffraction patterns of samples that did not have any concomitant crystallization of form II). In both forms I and II of (TMA)2(TBA)5(methanol)3, the asymmetric unit comprises a total of 10 independent molecules: five Htba+ cations, one Htma2− anion, one tma3− anion, and three methanol molecules. For each polymorph, the crystal structure comprises a sheetlike hydrogen-bonded array (see Figures 1a and 2a). The planes of the tma3− and Htma2− anions lie essentially in the plane of the sheet, and the −N+H3 groups of the Htba+ cations and the OH bonds of the methanol molecules lie close to this plane. The tert-butyl groups (TBA) and methyl groups (methanol) project outward from the sheets. For the discussion of the structures of forms I and II, it is convenient to define a transformed unit cell (a′, b′, c′) in each case [the original unit cells (a, b, c), before transformation, are specified in refs 9 and 10 respectively, and in the cif files

Figure 1. Crystal structure of form I of (TMA)2(TBA)5(methanol)3, viewed (a) perpendicular and (b) parallel to the plane of the hydrogen-bonded sheets. In part a, a single sheet is shown, and the tert-butyl groups of the Htba+ cations are omitted for clarity. The unit cell shown is the transformed unit cell (a′, b′, c′) defined in the text. The plane of the hydrogen-bonded sheet is the a′b′-plane [with respect to the original unit cell in the cif file, the plane of the sheet corresponds to (11̅1)]. The hydrogen-bonded ribbons indicated by the blue and red arrows are discussed in the text. In part b, the green arrow indicates the hydrogen-bonded sheet and the orange arrow indicates the aliphatic region containing the methyl and tert-butyl groups.

(Supporting Information)]. Specifically, the transformed unit cell in each case is defined according to the following criteria: the a′-axis is parallel to the hydrogen-bonded ribbon motif that is common to forms I and II (discussed in more detail below), the b′-axis is defined such that the a′b′-plane is parallel to the plane of the hydrogen-bonded sheet, and the c′-axis is the periodic repeat vector between adjacent hydrogen-bonded sheets. The transformed unit cells (a′, b′, c′) are shown in the plots of the crystal structures of form I (Figure 1) and form II (Figure 2). The lattice parameters for the transformed unit cells are as follows: form I, a′ = 20.2219(5) Å, b′ = 19.9987(6) Å, c′ = 10.3251(3) Å, α′ = 62.385(2)°, β′ = 48.527(2)°, γ′ = 85.268(2)°; form II, a′ = 20.1986(3) Å, b′ = 21.7294(4) Å, c′ = 10.2893(2) Å, α′ = 83.640(1)°, β′ = 49.011(1)°, γ′ = 113.437(1)°. From close inspection of the crystal structures of form I (Figure 1) and form II (Figure 2), it is clear that there are both similar aspects and significant differences between these structures, highlighted in particular by the overlay of the two structures in Figure 3. Within the sheets, forms I and II share a common hydrogen-bonded ribbon motif (parallel to the a′-axis of the transformed unit cell in each case), which runs horizontally in Figures 1a and 2a and is indicated as the region between the two dashed lines and marked by the red arrow (the symmetry related ribbon, generated by a crystallographic inversion center, is indicated by the blue arrow in Figures 1a and 2a). This ribbon motif involves an alternation of the 28

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Figure 2. Crystal structure of form II of (TMA)2(TBA)5(methanol)3, viewed (a) perpendicular and (b) parallel to the plane of the hydrogen-bonded sheets. In part a, a single sheet is shown, and the tert-butyl groups of the Htba+ cations are omitted for clarity. The unit cell shown is the transformed unit cell (a′, b′, c′) defined in the text. The plane of the hydrogen-bonded sheet is the a′b′-plane [with respect to the original unit cell in the cif file, the plane of the sheet corresponds to (112)̅ ]. The hydrogen-bonded ribbons indicated by the blue and red arrows are discussed in the text. In part b, the green arrow indicates the hydrogen-bonded sheet and the orange arrow indicates the aliphatic region containing the methyl and tert-butyl groups.

Figure 3. Overlay of the crystal structures of form I (cyan) and form II (magenta), revealing that there are both similar aspects and significant differences between these structures. The unit cell shown in each case is the transformed unit cell (a′, b′, c′), defined in the text and in Figures 1 and 2. The overlay has been constructed by aligning the a′axes of forms I and II parallel to each other and by orienting the a′-b′planes of forms I and II parallel to each other (the direction of view is perpendicular to the a′b′-plane of each structure). The tert-butyl groups of the Htba+ cations are omitted for clarity. The common hydrogen-bonded ribbon motif, which runs horizontally at the center of the plot, is essentially identical in the two structures and is overlaid directly in the plot. However, the positions of the adjacent ribbons (which also run horizontally at the top and bottom of the plot) relative to the central ribbon are different in forms I and II, leading to significant differences in the hydrogen-bonding arrangements linking adjacent ribbons. Some of these differences are highlighted by the yellow circles.

Htma2− and tma3− anions along the ribbon. Within the tma3−···Htma2−···tma3− repeat unit of these ribbons (periodic repeat distance along the ribbon: form I, a′ = 20.22 Å; form II, a′ = 20.20 Å), one tma3−/Htma2− pair are linked by a direct O−H···O hydrogen bond involving the −CO2H group of the Htma2− anion and one of the −CO2− groups of the tma3− anion, and the other two O atoms of these groups are bridged by an O···H−N−H···O hydrogen-bonding arrangement with an intervening −N+H3 group (this set of hydrogen bonds gives rise to a cyclic array denoted R33(10) in graph set notation11). The other Htma2−/tma3− pair in the ribbon are linked by the interaction of a −CO2− group from each of these anions with two intervening −N+H3 groups (giving rise to a cyclic array involving four N−H···O hydrogen bonds and denoted R34(10) in graph set notation). The primary difference between the structures of forms I and II concerns the relative disposition of adjacent ribbons of this type within the sheet and the nature of the hydrogen bonding between adjacent ribbons (which involves interactions with the −N+H3 groups of Htba+ cations and the OH bonds of methanol molecules located in the region between adjacent ribbons). In both forms I and II, all three N−H bonds in each of the five independent Htba+ cations are engaged as donors in N−H···O hydrogen bonding to O atoms of the Htma2− anion, the tma3− anion, or methanol molecules. With the exception of one specific N−H bond in form II (which forms a bifurcated hydrogen-bonding arrangement involving the two O atoms of a −CO2− group of the tma3− anion), all N−H···O hydrogen bonds involve a single O atom as the acceptor. In each polymorph, the O−H bond in each of the three independent methanol molecules is engaged both (i) as the donor in an

O−H···O hydrogen bond with an O atom of the Htma2− anion or the tma3− anion as the acceptor and (ii) as the acceptor in an N−H···O hydrogen bond with an N−H bond of an Htba+ cation as the donor. In both forms I and II, the hydrogen-bonded sheets are stacked in a manner that brings the tert-butyl groups and methyl groups together at the interface between adjacent sheets, with a similar perpendicular distance between the sheets in each case (form I, 6.47 Å; form II, 6.55 Å). Careful inspection of difference Fourier maps provides no evidence for disorder of the hydrogen-bonding arrangement in either form I or form II (for example, there is no evidence for partial occupancy of two hydrogen sites on any of the N···O distances that link the N atom of an Htba+ cation and the O atom of an Htma2− or tma3− anion, which would correspond to disorder between N−H···O and N···H−O hydrogen-bonding). Nevertheless, from knowledge of the average crystal structure determined from diffraction data, we cannot gain any insights on the possible occurrence of various types of dynamic disorder (such as 3-fold 120° jumps of the −N+H3 groups and/or the tert-butyl groups of the Htba+ cations, or methyl group rotations of the Htba+ cations or the methanol molecules) that are commonly observed in molecular crystals bearing these functional groups.12 29

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Matzger, A. J.; Rodriguez-Hornedo, N. Adv. Drug Delivery Rev. 2004, 56, 241−274. (g) Braga, D.; Grepioni, F. Chem. Commun. 2005, 3635−3645. (h) Bernstein, J. Chem. Commun. 2005, 5007−5012. (i) Chen, S. A.; Xi, H. M.; Yu, L. J. Am. Chem. Soc. 2005, 127, 17439− 17444. (j) Ahn, S.; Guo, F.; Kariuki, B. M.; Harris, K. D. M. J. Am. Chem. Soc. 2006, 128, 8441−8452. (k) Harris, R. K. Analyst 2006, 131, 351−373. (l) Price, S. L. Acc. Chem. Res. 2009, 42, 117−126. (m) Yu, L. Acc. Chem. Res. 2010, 43, 1257−1266. (n) Lim, G. K.; Fujii, K.; Harris, K. D. M.; Apperley, D. C. Cryst. Growth Des. 2011, 11, 5192− 5199. (o) Williams, P. A.; Hughes, C. E.; Lim, G. K.; Kariuki, B. M.; Harris, K. D. M. Cryst. Growth Des. 2012, 12, 3104−3113. (2) (a) Bond, A. D. CrystEngComm 2007, 9, 833−834. (b) Dunitz, J. D. CrystEngComm 2003, 5, 506. (3) All searches of the CSD were carried out on CSD version 5.33 (November 2011). (4) In our searches of the CSD in the present work, we consider only the results for well-determined structures, which we define as those satisfying the criteria for inclusion in the “best R-factor” list in the CSD (see: van de Streek, J. Acta Crystallogr., Sect. B 2006, 62, 567−579 ). (5) These structures have the following reference codes: (i) APESOE and APESOE01, (ii) CABZOU10 and CABZOU11, (iii) ENAZOI and ENAZOI01, (iv) MANMUJ02 and MANMUJ03, and (v) MAXDEV and MAXDEV01. (6) Duchamp, D. J.; Marsh, R. E. Acta Crystallogr., Sect. B 1969, 25, 5−19. (7) Herbstein, F. H.; Kapon, M.; Reisner, G. M. Acta Crystallogr. Sect. B 1985, 41, 348−354. (8) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112−122. (9) Form I of (TMA)2(TBA)5(methanol)3: triclinic, P1̅; T = 150(2) K; a = 10.3251(3) Å, b = 15.4590(4) Å, c = 17.7519(5) Å, α = 69.964(2)°, β = 86.592(2)°, γ = 78.556(2)°; V = 2608.96(13) Å3; Z = 2; crystal size = 0.35 × 0.30 × 0.25 mm3; no. of measured reflections = 15487; no. of independent reflections = 9892; Rint = 0.0232, R1 = 0.0488; wR2 = 0.1144. (10) Form II of (TMA)2(TBA)5(methanol)3: triclinic, P1̅; T = 150(2) K; a = 10.2893(2) Å, b = 15.5312(2) Å, c = 17.6113(3) Å, α = 92.3960(10)°, β = 106.2330(10)°, γ = 100.9840(10)°; V = 2639.14(8) Å3; Z = 2; crystal size = 0.35 × 0.30 × 0.15 mm3; no. of measured reflections = 15966; no. of independent reflections = 9995; Rint = 0.0266, R1 = 0.0539; wR2 = 0.1293. (11) (a) Etter, M. C. Acc. Chem. Res. 1990, 23, 120−126. (b) Etter, M. C.; MacDonald, J. C.; Bernstein, J. Acta Crystallogr., Sect. B 1990, 46, 256−262. (c) Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N. L. Angew. Chem., Int. Ed. 1995, 34, 1555−1573. (12) (a) Clough, S.; Heidemann, A.; Horsewill, A. J.; Lewis, J. D.; Paley, M. N. J. J. Phys. C: Solid State Phys. 1982, 15, 2495−2508. (b) Riddell, F. G.; Arumugam, S.; Harris, K. D. M.; Rogerson, M.; Strange, J. H. J. Am. Chem. Soc. 1993, 115, 1881−1885. (c) Beckmann, P. A.; Alhallaq, H. A.; Fry, A. M.; Plofker, A. L.; Roe, B. A.; Weiss, J. A. J. Chem. Phys. 1994, 100, 752−753. (d) Kitchin, S. J.; Ahn, S. B.; Harris, K. D. M. J. Phys. Chem. A 2002, 106, 7228−7234. (e) Kitchin, S. J.; Tutoveanu, G.; Steele, M. R.; Porter, E. L.; Harris, K. D. M. J. Phys. Chem. B 2005, 109, 22808−22813. (13) (a) Burger, A.; Ramberger, R. Mikrochim. Acta 1979, 2, 259− 271. (b) Burger, A.; Ramberger, R. Mikrochim. Acta 1979, 2, 273−316. (14) (a) Steed, J. W. CrystEngComm 2003, 5, 169−179. (b) Anderson, K. M.; Steed, J. W. CrystEngComm 2007, 9, 328− 330. (c) Anderson, K. M.; Goeta, A. E.; Steed, J. W. Cryst. Growth Des. 2008, 8, 2517−2524. (d) Anderson, K. M.; Probert, M. R.; Goeta, A. E.; Steed, J. W. CrystEngComm 2011, 13, 83−87. (15) Shieh, H.-S.; Hoard, L. G.; Nordman, C. E. Acta Crystallogr., Sect. B 1982, 38, 2411−2419. (16) Parrish, D. A.; Deschamps, J. R.; Gilardi, R. D.; Butcher, R. J. Cryst. Growth Des. 2008, 8, 57−62. (17) Batsanov, A. S.; Collings, J. C.; Ward, R. M.; Goeta, A. E.; Porrès, L.; Beeby, A.; Howard, J. A. K.; Steed, J. W.; Marder, T. B. CrystEngComm 2006, 8, 622−628.

In assessing the relative stabilities among a set of polymorphs, higher density is often associated with greater stability, as conveyed by the so-called density rule13 (although many exceptions to this rule are known). In the present case, given that the densities calculated from the crystal structures at 150 K (form I, 1.115 g cm−3; form II, 1.102 g cm−3) are very similar, we refrain from speculating on the relative stabilities of forms I and II on the basis of the density rule. Throughout our studies of the polymorphs of (TMA)2(TBA)5(methanol)3, no transformations between forms I and II have been observed under ambient conditions, and DSC data recorded from ambient temperature to −100 °C show no thermal events for either polymorph. However, on standing in an ambient atmosphere, both polymorphs are highly susceptible to loss of methanol, resulting in the same crystalline phase in each case (crystal structure determination of this phase from powder X-ray diffraction data is currently in progress). While many crystal structures have high numbers of independent molecules in the asymmetric unit,14 there are only three cases of polymorphism (assessed4 from the CSD) in which at least two polymorphs have 10 or more independent molecules in the asymmetric unit: cholesterol hemiethanolate15 [each of the two reported polymorphs has eight cholesterol molecules and four ethanol molecules in the asymmetric unit], picryl bromide16 [the five reported polymorphs have 6 (α polymorph), 3 (β), 12 (γ), 12 (δ), and 18 (ε) independent molecules in the asymmetric unit], and 4-ethynyl-N,Ndimethylaniline17 [each of the two reported polymorphs has 12 independent molecules in the asymmetric unit]. Thus, the (TMA)2(TBA)5(methanol)3 system reported here ranks fourth highest in terms of the number of independent molecules in the asymmetric unit for a pair of polymorphic structures. In addition to the significance of such materials within the context of polymorphism research, the discovery of polymorphic systems with large numbers of independent molecules in the asymmetric unit is also relevant within the context of high Z′ structures, which have been a subject of increasing interest in recent years.14

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ASSOCIATED CONTENT

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AUTHOR INFORMATION

* Supporting Information S

Crystallographic information (cif) files for the two polymorphs (forms I and II) of (TMA)2(TBA)5(methanol)3. This material is available free of charge via the Internet at http://pubs.acs.org.

Corresponding Author

*E-mail: HarrisKDM@cardiff.ac.uk. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to Cardiff University for financial support. REFERENCES

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