Triphenylphosphine Oxide

Jun 14, 2013 - Nucleation in the p-Toluenesulfonamide/Triphenylphosphine Oxide Co-crystal System ... Fax: +353 61 213529. Synopsis. Co-crystal nucleat...
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Nucleation in the p‑Toluenesulfonamide/Triphenylphosphine Oxide Co-crystal System Denise M. Croker,*,†,§ Roger J. Davey,‡ Åke C. Rasmuson,† and Colin C. Seaton† †

Solid State Pharmaceutical Cluster, Materials and Surface Science Institute and the Department of Chemical and Environmental Sciences, University of Limerick, Limerick, Ireland ‡ School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom ABSTRACT: Nucleation has been studied in pure co-crystal and mixed cocrystal phase regions of the ternary phase diagram (TPD) in acetonitrile at 20 °C using cooling crystallization experiments. Direct nucleation of each of the co-crystal phases in this system was independently observed in regions of the TPD where each is stable. In mixed regions, regions where either a co-crystal and a coformer, or both co-crystals, are stable, the phase that initially nucleated was a function of the mass composition in that region. The relative amount of each phase nucleating could be controlled by adjusting the relative mass fraction of each component. The kinetic return to equilibrium was also observed as the systems were held over time, with the selected mass fractions always returning to the equilibrium dictated by the TPD after 24 h.

INTRODUCTION The creation of novel solid-state materials with predefined physical properties is one of the primary objectives of crystal engineering research. Studies into multicomponent crystalline materials, such as co-crystals and salts, have become a key component of such research. The addition of another compound alters the crystal structure, adjusting the physicochemical properties of the parent material but without chemically altering the material. 1−6 This has potential applications in many fields of science and engineering; the application to modify the physicochemical properties of active pharmaceutical ingredients (APIs) has attracted the greatest interest.7−12 In general, the research into multicomponent crystals has focused on the identification and structural characterization of new phases. Comparatively, little work has been undertaken on the nucleation and crystal growth processes of such materials. While the synthesis of new cocrystal phases is readily achieved on a laboratory scale through evaporative crystallization or solid-state grinding techniques, the large-scale production of such materials will require a stronger understanding of the processes that control the nucleation and growth of these materials to allow for a controlled scale-up of the processes. For solution-based cocrystallization methods, the key source of information for the experimental design is the ternary phase diagram (TPD, Figure 1),13−15 which locates the compositional regions where the different phases are thermodynamically stable for a given temperature and pressure. The relative solubility of the two components will adjust the size and location of the different compositional regions and in the case of systems with two cocrystals of differing composition, different solvents may adjust © 2013 American Chemical Society

Figure 1. Schematic ternary phase diagram for a system with a single congruently dissolving 1:1 co-crystal phase. Region 1, undersaturated solution; region 2, pure A; region 3, 1:1 co-crystal; region 4, pure B; region 5, mixture of A and a 1:1 co-crystal; region 6, mixture of B and 1:1 co-crystal.

the relative stability.16−19 A co-crystal may be defined as congruent or incongruent depending on how it dissolves in a solvent system. If co-crystal dissolution results in the generation Received: May 20, 2013 Revised: June 13, 2013 Published: June 14, 2013 3754 | Cryst. Growth Des. 2013, 13, 3754−3762

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1.5418 Å), run at 40 kV and 35 mA, over an angular range of 5−35° 2θ. Optical and Scanning Electron Microscopy. Optical microscopy was performed using a Zeiss Axioplan 2 polarizing microscope and the Linksys image capture software. SEM images were collected on a JEOL CarryScope JCM-5700 scanning electron microscope. Nucleation Experiments. Initial experiments were performed on a 1 mL scale, using the Crystal 16 system from Avantium Technologies. From the previously derived ternary phase diagram (Figure 3),18 a number of compositions were prepared in the regions where the 3:2 or 1:1 co-crystal are independently thermodynamically stable at 20 °C (Table 1). These solutions were heated to 60 °C, held for one hour to ensure complete dissolution, subsequently cooled at 1 °C/min to 20 °C and aged for one hour. The resulting solids were filtered, dried, and analyzed with powder X-ray diffraction to identify the phase composition. Reference PXRD patterns for the 3:2 and 1:1 co-crystals were generated from their respective crystallographic information files (CIF) using Mercury 2.4.27,28 Subsequent experiments were performed in a HEL polyblock, an automated temperature-controlled multiwell reaction platform. An aluminum block insert was placed in one well giving parallel temperature control over sixteen 2 mL vials. Mass fractions of TSA, Ph3PO, and MeCN, on a total mass basis, were selected to correspond to regions in the TPD where two phases can coexist in equilibrium, namely TSA and the 3:2 co-crystal, the 3:2 and the 1:1 co-crystal, and the 1:1 co-crystal and Ph3PO (Table 1). The solutions were heated to 60 °C to ensure complete dissolution, cooled to 20 °C at 1 °C/min, and held for 30 min at 20 °C. At this time the solids were isolated by filtration, dried, and analyzed with PXRD and SEM. For the three circled compositions in Figure 3, the solution was heated to 60 °C on a 5 mL scale and approximately 1 mL of the clear solution was transferred at temperature to three individual preheated glass vials. These vials were cooled individually as described above and held for 30 min and 4 and 24 h, respectively. This provided for an analysis of phase composition as a function of time. This methodology was necessary because extraction of samples from a standard cooling experiment would adjust the total mass composition and so affect the results over time. A final study focused specifically on the region of the TPD where TSA and the 3:2 co-crystal may coexist in equilibrium. Compositions were selected such that the solvent mass fraction was kept constant, and the relative amounts of TSA and Ph3PO were varied (horizontal motion across the TPD, Figure 4). These samples were heated to 60 °C to ensure full dissolution, cooled at 1 °C/min to 20 °C, and held for 24 h to ensure that equilibrium was reached. The individual supersaturation of each phase was calculated by the following method: (1) The eutectic concentration was used as the equilibrium solubility for any mass fraction in this region. For TSA, the equilibrium solubility was simply taken as the concentration of TSA at the eutectic point. For the 3:2 cocrystal, a solubility product was calculated from the eutectic concentration using the formula, Ksp3:2 = [TSAEu]3[Ph3POEu]2. This was used as a relative measurement of the solubility of the 3:2 co-crystal. (2) TSA supersaturation was then calculated as the concentration of TSA in solution when the total mass fraction was fully dissolved divided by the concentration of TSA at the eutectic concentration.

of a stoichiometric solution (identical to the co-crystal stoichiometry), the co-crystal is said to display congruent dissolution. Incongruent dissolution occurs when co-crystal dissolution is accompaniment by a phase change in the solid form and a nonstoichiometric solution is generated. For example, benzoic acid forms two co-crystals with isonicotinamide, one with a 1:1 composition and one with a 2:1 composition. Both phases are stable in aqueous solutions;16 however, the 2:1 phase is only metastable in alcoholic solutions and the addition of crystals of the 2:1 phase to a saturated solution dissolve and nucleate as the 1:1 co-crystal.17 Thus, designing crystallization conditions to grow a specified phase requires consideration of the stability and solubility of the components and their effect on the shape of the regions within the TPD. Crystals of the previously considered metastable 2:1 malic acid/caffeine co-crystal20 were obtained by crystallization from ethyl acetate, a solvent in which the components have similar relative solubilities, thus increasing the size of the region of 2:1 phase stability.21 While the TPD provides information on the thermodynamic stability of the different phases, the crystallization process is equally influenced by kinetics as by thermodynamics; this is highlighted by the discovery of a second polymorph of the 1:1 maleic acid/caffeine co-crystal, which only occurred in one crystallization batch.21 Reported studies into the kinetics of cocrystallization include the alteration of the metastable zone width with composition,17 in situ monitoring of the relative growth rates of different phases,22,23 development of suitable scale-up procedures,24 and the solution mediated transformations of single components into co-crystal phases25 and between co-crystals.26 This work reports how the choice of starting composition influences the nucleation and growth of the differing phases within the various regions of a TPD. The co-crystal forming system p-toluenesulfonamide/triphenylphosphine oxide (TSA/Ph3PO) in acetonitrile has been selected for study as the TPD previously constructed18 and indicates the presence of a congruently dissolving 1:1 co-crystal and an incongruently dissolving 3:2 co-crystal phase (Figure 2).

Figure 2. Chemical structure of (a) p-toluenesulphonamide, (B) triphenylphosphine oxide and crystal structure of the 3:2 co-crystal, and (d) the 1:1 co-crystal formed between these two solids.

Experimental Section. p-Toluenesulfonamide and triphenylphosphine oxide were obtained from Sigma-Aldrich and used as received. Reagent-grade acetonitrile was used as received. Powder Diffraction. Powder diffraction data were collected on either a Philips X’Pert-MPD PRO or a Rigaku Miniflex diffractometer with nickel-filtered copper Cu Kα radiation (λ = 3755 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 3. Ternary phase diagram for TSA/Ph3PO in acetonitrile at 20 °C. The regions where a single crystalline phase is stable are highlighted (TSA only, green; Ph3PO only, yellow; 3:2 co-crystal, blue; 1:1 co-crystal, red). Experimental points studied are indicated within each region by corresponding symbols in Table 1.

Table 1. Relative Mass Fractions of Trial Points Studied relative mass fraction (total mass basis) symbol




0.38 0.30 0.19 0.20 0.24 0.27 0.20 0.15 0.09 0.12 0.14 0.19 0.05 0.08

0.07 0.05 0.09 0.15 0.13 0.19 0.20 0.15 0.12 0.18 0.16 0.26 0.24 0.32

0.55 0.60 0.72 0.65 0.63 0.54 0.60 0.7 0.79 0.70 0.70 0.55 0.71 0.60

▲ ×


region in TPD TSA/3:2 co-crystal 3:2 co-crystal

3:2 co-crystal/1:1 co-crystal 1:1 co-crystal

1:1 co-crystal/Ph3PO


2 2 2 1 1 1 2 2 2 1 1 1 2 2


Nucleation of Single Co-Crystal. Cooling crystallizations in the independent regions of the TPD where the co-crystals are the only stable phases resulted in only the expected cocrystal formation (Figure 5). While variations in observed peak intensity are obvious in the recorded patterns, due to inconsistent mass in each sample and the lack of grinding in sample preparation, no additional peaks can be identified. In each case, a pure co-crystal was obtained within one hour after reaching the 20 °C set point and so direct nucleation of the relevant crystal phase is assumed to have occurred. It is worth

(3) The supersaturation of the 3:2 co-crystal was the solubility product at the sample concentration divided by the solubility product at the C1 eutectic concentration. S3:2 = [TSA]3 [Ph3PO]2 /[K sp 3:2]

experiment scale (mL)


The calculated supersaturation values are presented in Table 2. 3756 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 4. TPD indicating the experimental points examined across the mixed TSA/3:2 co-crystal region.

temperature as the solubility of both coformers changes, thus changing the shape and size of each region. It was not necessary to determine the TPD as a function of temperature because all sampling took place at 20 °C. The morphologies of the two cocrystals are similar with block-type crystals obtained in each case (Figure 6), although for the compositions used, greater faceting is observed on the 1:1 co-crystal than the 3:2. Nucleation of Co-Crystal Mixtures. In the mixed region where both the 1:1 and 3:2 co-crystals can coexist in equilibrium, the solid phase present 30 min after nucleation is dependent on the overall solution composition. The 3:2 cocrystal dominates the 0.15:0.15:0.70 sample after 30 min, whereas the 1:1 co-crystal dominates the alternate 0.20:0.20:0.60 sample after the same period of time (Figure 7). This suggests that both co-crystals do not initially nucleate concomitantly in this region where they are both stable;

Table 2. Compositions and Supersaturations of Systems Studied in Mixed TSA:3:2 Co-crystal Stability Region mass fraction composition (TSA:Ph3PO:MeCN)

concentration (mol dm−3) (TSA, Ph3PO)


supersaturation (TSA, 3:2)a

0.32:0.08:0.60 0.35:0.05:0.60 0.37:0.03:0.60

2.45, 0.38 2.7, 0.23 2.84, 0.14

2.12 1.02 0.45

1.69, 482.4 1.83, 232 1.96, 102.0

Eutectic compositions, [TSA] = 1.45 mol dm−3, [TPPO] = 0.04 mol dm−3.


noting that the phase diagram for the system was determined at 20 °C, and so the equilibrium it predicts is valid at 20 °C only. This is why each experiment was allowed to reach 20 °C before the solid was sampled. The phase diagram will change with

Figure 5. PXRD patterns of solids recovered from crystallization at the indicated mass fraction compositions in 1:1 (left) and 3:2 (right) co-crystal regions in the TSA-Ph3PO-MeCN ternary-phase system. Dashed lines represent the theoretical pattern for the 1:1 and 3:2 co-crystal, respectively. 3757 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 6. SEM images of the crystalline product harvested 30 min after crystallization for the (a) 1:1 co-crystal and (b) 3:2 co-crystal obtained by crystallization in regions of single-phase stability.

Figure 7. PXRD patterns of solids recovered from nucleation experiments in the mixed 3:2 co-crystal/1:1 co-crystal region of the TPD, as defined in Table 1.

Figure 8. SEM images of the crystalline product harvested 30 min after crystallization for the (a) 0.15:0.15:0.7 (mostly 1:1 co-crystals) and (b) 0.20:0.20:0.60 compositions (mostly 3:2 co-crystals).

Recall at 30 min, the 1:1 co-crystal dominated the sample; at

different amounts of co-crystal nucleate initially rendering one co-crystal undetectable or the growth rates of the two cocrystals are very different at the different starting compositions. Examination of the behavior of the 0.20:0.20:0.60 sample as a function of time clarifies these scenarios

4 h, the 3:2 co-crystal is present with very little trace of the 1:1 co-crystal. At 24 h, both co-crystals are present together as dictated by the TPD at equilibrium. This indicates a dynamic 3758 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 9. PXRD patterns for the samples from the 1:1/Ph3PO mixed region of the TPD.

Figure 10. SEM images of the crystalline product harvested 30 min after crystallization for (a) 0.05:0.24:0.71 (mostly Ph3PO) and (b) 0.08:0.32:0.60 compositions (mixture of 3:2, 1:1 co-crystals, and Ph3PO).

Nucleation of Mixtures of 1:1 Co-Crystal and Ph3PO. Within the region where the 1:1 co-crystal and Ph3PO are both stable, differing behavior in relation to the concentration of the two components (Figure 9) is again shown. For the mass composition 0.05:0.24:0.71, Ph3PO dominates the sample after 30 min with only one small reflection indicative of the 1:1 cocrystal present at 2θ ≈ 10°. In contrast, for the 0.08:0.32:0.60 composition, a mixture of the 3:2 co-crystal, the 1:1 co-crystal, and Ph3PO initially grows, which upon aging, the 3:2 co-crystal dissolves and leaves the sample consisting of the 1:1 co-crystal and Ph3PO only. The presence of three solid phases requires one to be a metastable form, in this case the 3:2 co-crystal, which is confirmed by its dissolution upon standing. However, crystallization of the 3:2 co-crystal suggests either the system must pass through a region of 3:2 co-crystal stability at a higher temperature during the cooling process or the crystallization of the 3:2 co-crystal is kinetically favored in this solvent. As the TPD for higher temperatures are not available currently for this system, identification of which pathway occurs cannot currently be confirmed. The crystals from the lower supersaturation composition (0.05:0.24:0.71) again show better quality (Figure

system where solid-phase composition is changing as the system strives for equilibrium. Comparison of the morphology of the crystals obtained with those grown from the region where the pure co-crystal phase is stable show a modification of the 3:2 system. These crystals are elongated and result in the formation of rod- and needle-shaped crystals (Figure 8b), while the 1:1 is unchanged (Figure 8a). There are two possible causes of this morphological change, one may be a greater relative increase in the supersaturation level of the 3:2 co-crystal compared to the 1:1 [the ratio of 3:2 supersaturation to 1:1 supersaturation is 20.8 (0.15:0.15:0.70) and 78.5 (0.20:0.20:0.60)], causing the faster growth of the 3:2 co-crystal or the presence of excess TSA in the solution acting as a habit-modifying impurity. To confirm which mechanism is dominant, further work is required. This would require crystallizations at differing supersaturation and compositions levels to confirm the variation in morphology with experimental conditions. This could be combined with molecular modeling of the interactions between crystal surfaces and the different components to identify alterations to the attachment energies of the crystal faces. 3759 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 11. PXRD patterns of the solid phase recovered from the mixed TSA/3:2 co-crystal region at set mass fractions and times. Theoretical patterns are given for 3:2 co-crystal and TSA phases.

Figure 12. SEM images of the crystalline product harvested 30 min after crystallization for the (a) 0.38:0.07:0.55 (TSA and 3:2 co-crystal mixture) and (b) 0.30:0.05:0.65 compositions (predominately 3:2 co-crystal).

achieved on moving across the region in a controlled manner (Figure 13). Moving from left to right across the region represents an increase in the proportion of Ph3PO present; at a constant solvent mass fraction, this corresponds to a decrease in the overall TSA:Ph3PO ratio. Sample 37:3:60 (2.84 M TSA) lies at the most left-hand side of the region. This solution composition yielded a mixture of TSA/3:2 co-crystals, which was dominated by TSA. Moving to sample 35:5:60 resulted in an increase in the amount of 3:2 co-crystal in the sample, and a further increase was observed in sample 32:8:60. This is somewhat intuitive, as on moving from left to right across this region of the TPD, mass composition is approaching the pure 3:2 co-crystal region. The supersaturation of TSA and the 3:2 co-crystal was calculated for each sample using the methodology outlined above and is presented graphically in Figure 14. The supersaturation experienced by TSA decreases on moving from left to right across the region, in good agreement with experimental results.

10a), while the solid phase from the 0.08:0.32:0.60 composition displays a wide variety of morphologies (Figure 10b), with more rodlike crystals being obtained. The partially dissolved phase is expected to be the metastable 3:2 co-crystal. Nucleation of Mixtures of 3:2 Co-Crystal and TSA. Within the mixed TSA/3:2 co-crystal region, nucleation and growth occurred for both solution compositions after 30 min. The 0.38:0.07:0.55 sample yielded a reasonably even mixture of TSA and the 3:2 co-crystal (Figure 11), while the 0.30:0.05:0.65 composition resulted in a dominant 3:2 phase with only a small trace of TSA present. The behavior of this composition with time was subsequently investigated and found to remain consistent after 4 and 24 h aging (Figure 12). As with the mixed 1:1/3:2 co-crystal region, the crystals of the 3:2 cocrystal obtained exhibit a more rodlike morphology compared to those grown in the pure 3:2 co-crystal region. In the 0.38:0.07:0.55 composition, the TSA grows as poorly formed plates, which again may be due to the high supersaturation for this phase in this composition (3780 C/C*). Further manipulation of solution composition with the mixed TSA/3:2 co-crystal region illustrated that a systematic change in the relative amounts of TSA and 3:2 co-crystal can be

CONCLUSIONS The nucleation and growth of co-crystals formed between TSA and Ph3PO from acetonitrile has been investigated across the 3760 | Cryst. Growth Des. 2013, 13, 3754−3762

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Figure 13. PXRD patterns of solids recovered from the mixed TSA/3:2 co-crystal region as a function of changing TSA:Ph3PO. Reference patterns for pure TSA and the 3:2 co-crystal are included.

Figure 14. Calculated supersaturation for TSA and the 3:2 co-crystal for the experimental points in the mixed TSA/3:2 co-crystal region of the TPD as a function of changing TSA/Ph3PO.

different regions of the ternary-phase diagram. Direct nucleation of each of the pure co-crystals was independently observed from solution at a number of different solution mass compositions within their respective regions of stability in the TPD. Within regions where two phases are stable, the initial crystallizing phase is dependent upon the overall solution composition, and in turn the concentration of the two species, which also affects the morphology of the crystal obtained. Prior to reaching equilibrium kinetic factors such as nucleation or growth rates can influence the composition of the crystallizing phase, with the result that the first phase to nucleate may not correspond to the thermodynamically stable phase predicted by the TPD. When equilibrium is reached, the TPD is obeyed. Within a given region, the relative amounts of two components can be adjusted by moving horizontally across the phase

diagram. A method of calculating supersaturation in ternary systems was proposed and used to better understand this nucleation behavior. Co-crystallization is a controllable unit operation when full knowledge of stability in the system via the ternary-phase diagram is available. This is demonstrated in this study, as selective crystallization of a desired co-crystal form in a pure state was achieved when the starting composition was dictated by the TPD.


Corresponding Author

*E-mail: [email protected]. Tel: +353 51 601655. Fax: +353 61 213529. Present Address §

MSD Ballydine, Kilsheelan, Clonmel, Co. Tipperary, Ireland.

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The authors declare no competing financial interest.

ACKNOWLEDGMENTS This publication has emanated from research conducted with the financial support of Science Foundation Ireland under Grant Number 07/SRC/B1158.


(1) Aakeröy, C. B.; Salmon, D. J. CrystEngComm 2005, 7, 439−448. (2) Bolton, O.; Matzger, A. J. Angew. Chem., Int. Ed. 2011, 50, 8960− 8963. (3) Huang, N.; Rodriguez-Hornedo, N. CrystEngComm 2011, 13, 5409−5422. (4) Frišcǐ ć, T.; Jones, W. J. Pharm. Pharmacol. 2010, 62, 1547−1559. (5) Stahly, G. P. Cryst. Growth Des. 2009, 9, 4212−4229. (6) Desiraju, G. R. Angew. Chem., Int. Ed. 2007, 46, 8342−8356. (7) Leung, D. H.; Lohani, S.; Ball, R. G.; Canfield, N.; Wang, Y.; Rhodes, T.; Bak, A. Cryst. Growth Des. 2012, 12, 1254−1262. (8) Chow, S. F.; Chen, M.; Shi, L.; Chow, A. H. L.; Sun, C. C. Pharm. Res. 2012, 29, 1854−1865. (9) Schultheiss, N.; Roe, M.; Boerrigter, S. X. M. CrystEngComm 2010, 13, 611. (10) Schultheiss, N.; Newman, A. W. Cryst. Growth Des. 2009, 9, 2950−2967. (11) Almarsson, Ö .; Zaworotko, M. J. Chem. Commun. (Cambridge, U.K.) 2004, 1889−1896. (12) Shan, N.; Zaworotko, M. J. Drug Discovery Today 2008, 13, 440−446. (13) Chiarella, R. A.; Davey, R. J.; Peterson, M. L. Cryst. Growth Des. 2007, 7, 1223−1226. (14) Maheshwari, C.; Jayasankar, A.; Khan, N. A.; Amidon, G. E.; Rodriguez-Hornedo, N. CrystEngComm 2009, 11, 493−500. (15) Ainouz, A.; Authelin, J.-R.; Billot, P.; Lieberman, H. Int. J. Pharm. 2009, 374, 82−89. (16) Seaton, C. C.; Parkin, A.; Wilson, C. C.; Blagden, N. Cryst. Growth Des. 2009, 9, 47−56. (17) Boyd, S.; Back, K. R.; Chadwick, K.; Davey, R. J.; Seaton, C. C. J. Pharm. Sci. 2010, 99, 3779−3786. (18) Croker, D. M.; Foreman, M. E.; Hogan, B. N.; Maguire, N. M.; Elcoate, C. J.; Hodnett, B. K.; Maguire, A. R.; Rasmuson, Å. C.; Lawrence, S. E. Cryst. Growth Des. 2012, 12, 869−875. (19) Zhang, S.; Rasmuson, Å. C. Cryst. Growth Des. 2013, 13, 1153− 1161. (20) Guo, K.; Sadiq, G.; Seaton, C. C.; Davey, R. J.; Yin, Q. Cryst. Growth Des. 2010, 10, 268−273. (21) Leyssens, T.; Springuel, G.; Montis, R.; Candoni, N.; Veesler, S. Cryst. Growth Des. 2012, 12, 1520−1530. (22) Gagniere, E.; Mangin, D.; Puel, F.; Bebon, C.; Klein, J.-P.; Monnier, O.; Garcia, E. Cryst. Growth Des. 2009, 9, 3376−3383. (23) Gagniere, E.; Mangin, D.; Puel, F.; Rivoire, A.; Monnier, O.; Garcia, E.; Klein, J.-P. J. Cryst. Growth 2009, 311, 2689−2695. (24) Sheikh, A. Y.; Rahim, S. A.; Hammond, R. B.; Roberts, K. J. CrystEngComm 2009, 11, 501−509. (25) Gagniere, E.; Mangin, D.; Puel, F.; Valour, J.-P.; Klein, J.-P.; Monnier, O. J. Cryst. Growth 2011, 316, 118−125. (26) Croker, D. M.; Davey, R. J.; Rasmuson, Å. C.; Seaton, C. C. CrystEngComm 2013, 15, 2044−2047. (27) Macrae, C. F.; Bruno, I. J.; Chisholm, J. A.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Rodriguez-Monge, L.; Taylor, R.; de Streek, J. V.; Wood, P. A. J. Appl. Crystallogr. 2008, 41, 466−470. (28) Macrae, C. F.; Edgington, P. R.; McCabe, P.; Pidcock, E.; Shields, G. P.; Taylor, R.; Towler, M.; van de Streek, J. J. Appl. Crystallogr. 2006, 39, 453−457.

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