ARTICLE pubs.acs.org/crystal
Precise Habit Modification of Polar DL-Alanine Crystal by Control of Supersaturation Guangjun Han,*,† Pui Shan Chow,† and Reginald B. H. Tan*,†,‡ †
Institute of Chemical and Engineering Sciences, A-STAR (Agency for Science, Technology and Research), 1, Pesek Road, Jurong Island, Singapore 627833 ‡ Department of Chemical and Biomolecular Engineering, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 ABSTRACT: It has long been reported that a DL-alanine crystal grows considerably faster from its flat c end than from its pointed +c end, showing typical unidirectional growth from the c direction and exhibiting a polar needlelike habit. Surprisingly, our new experimental results reveal that the normally slow-growing hemihedral faces at the pointed +c end can undergo fast growth at high supersaturations, contrary to the postulation of the “relay” mechanism. At the same time, a new (001) face at the +c end develops, causing the initially pointed +c end to become flat and leading to a habit modification from needlelike to rodlike with an increase of supersaturation. Furthermore, both the flat (001) face at the +c end and the (001) face at the c end can grow equally fast, and hence, the usually observed unidirectional growth from the c direction does not hold any more. These new observations are discussed and rationalized.
’ INTRODUCTION Polar organic crystals are noncentrosymmetric in packing. They possess a polar axis, with different functional groups exposed at the opposing ends of the polar axis.1,2 Given such a structural feature, polar organic crystals generally have salient properties (e.g., large nonlinear optical response and fast response time3), and hence, they play an important role in various applications including nonlinear optics.1 6 For the characterization and application, single polar crystals with good quality are often required, and the crystal size has to be large enough.4 Unfortunately, polar crystals, generally grown from solution, often suffer from growth inhibition (even zero growth rate) along one of the polar directions.4,7 9 Increasing the supersaturation may substantially increase the growth along the other polar direction (i.e., the fast growing direction), resulting in unstable growth and poor quality of the single crystal.4 To address this issue, it is required to control (promote and/or inhibit) the growth rates of certain particular faces of a single crystal, via various techniques including addition of additive, using different solvents and manipulations of supersaturation.10 13 Furthermore, the face growth rates determine the habit of bulk crystals while the crystal habit can exert a great impact14 on the downstream processing (e.g., filtration and drying) and formulation of the bulk crystals. Also, crystal growth kinetics plays a part in determining the outcome of polymorphic crystallization, as alteration of crystal growth kinetics of polymorphs by choice of additives and/or solvents can offer a means for polymorph control,13,15 17 which is crucial in many industries (especially in pharmaceutical industry).18 21 r 2011 American Chemical Society
In general, to produce crystals with proper sizes, desired habits, and required polymorphs, it is essential to understand crystal growth mechanisms1,4,7 9 and the effects of supersaturation, solvent, and additive10 13 on crystal face growth kinetics. Despite the great efforts dedicated to crystal growth kinetics,1,7 9,22 it has been, however, challenging to precisely control crystal face growth rates, because the fundamental understanding of crystallization is still limited.18,22 24 9 DL-Alanine is a typical polar crystal (space group Pna21) and 6 potentially useful in application of nonlinear optics. As a simple amino acid, it is highly water-soluble25 and exists as zwitterions [CH3CH(NH3+)COO ]1,26 in aqueous solution. Upon crystallization, the obtained DL-alanine crystal is packed in such a way that the zwitterions are arranged in a head-to-tail orientation along the polar c-axis. This particular molecular orientation in packing leads to the fact that the c end exposes the carboxylate (COO ) groups and the +c end exposes the amino (NH3+) groups.9 Different crystalline structures (i.e., polymorphs) of 1 DL-alanine have not been reported before. 1,9,26 Previous studies revealed that the relative face growth rates of DL-alanine crystals in aqueous solutions can differ to a large extent, leading to diverse crystal habits. On the one hand, it was discovered9,26 that DL-alanine crystals can be needlelike and elongated along the polar c-axis, with the flat c end exhibiting the rough (001) face while the identifiable pointed +c end exhibits the smooth hemihedral {201} and {011} faces. These Received: April 28, 2011 Revised: June 10, 2011 Published: July 01, 2011 3941
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Figure 2. Growth rates of DL-alanine, showing much faster growth along b-axis than along c-axis at low supersaturations (σ e 1.75). The error bar is 20%.
Figure 1. Images of a growing DL-alanine seed crystal, illustrating the very slow growth along the c-axis and measurable growth along the b-axis at a supersaturation σ = 1.75.
elongated crystals indicate that the resulting growth rate of the faces at the +c and c ends is faster than those of the side {210} faces. Furthermore, it was also found9,26 that the growth along the c-axis is unidirectional, primarily determined by the growth from the c direction. On the other hand, our recent study1 showed that in a range of low supersaturations, the growth rates of the faces at both the +c and the c ends are far slower than those of the side {210} faces, resulting in prismatic pyramidal crystals. As suggested,1 these diverse habits of DL-alanine crystals grown from aqueous solutions would be supersaturation-dependent. Unfortunately, the quantitative relationship between the face growth rate (hence habit) and the supersaturation has not been well established. This is due to the unavailable values of the associated supersaturations9,26 at which the experiments for DL-alanine crystal growth rates were performed. The reason for the unavailability of supersaturations is probably because a supersaturation was normally generated by uncontrolled evaporation of DL-alanine solution, and hence, it was operationally difficult to determine the generated supersaturation during in situ crystal growth experiments under optical microscope. In this work, we systematically measure the growth rates of DL-alanine seed crystals in pure (i.e., additive-free) DL-alanine aqueous solutions at known supersaturations generated by cooling. Our new observations on DL-alanine growth behavior and the precise crystal habit modification are presented. What is the most unexpected is that the hemihedral faces at the pointed +c end, normally slow growing, undergo fast growth at high supersaturations, which cannot be explained by the “relay” mechanism.9
’ EXPERIMENTAL SECTION DL-Alanine (99%) was from Sigma-Aldrich and used as received. Ultrapure water (Millipore, resistivity 18.2 MΩcm and filtered with pore size 0.22 μm) was used for solution preparation. The reported1 solubility of DL-alanine in H2O at 23 °C, 16.1 g/100 g H2O, was applied for the calculation of supersaturation σ (which is defined as σ = C/Csat, where C and Csat are the actual DL-alanine concentration and DL-alanine solubility, respectively). The supersaturation was limited to 2.20, as massive
three-dimensional nucleation quickly happened once a DL-alanine seed crystal came into contact with the solution at a supersaturation higher than 2.20, leading to the failure of the experiment for a growth rate of a seed crystal. DL-Alanine needlelike seed crystals were prepared by evaporation of concentrated additive-free DL-alanine aqueous solutions at room temperature (∼23 °C). A Bruker D8 Advance Diffractometer was employed to verify the crystalline structure of the associated DL-alanine crystals wherever applicable. For the measurement of DL-alanine growth rate at 23 °C, the same experimental procedure described in our previous work1 was used here. An additive-free DL-alanine aqueous solution (pH ∼6.2) was prepared at an elevated temperature. The obtained warm solution in a jacketed beaker was then cooled to 23 °C using a water circulator (with a readability 0.01 °C) to generate a supersaturation. About 12 mL of the supersaturated solution was gently filtered (0.22 μm, FroFill membrane syringe filter) into a thermally pre-equilibrated (at 23 °C) glass crystallization dish (6 cm in diameter) in which a single DL-alanine seed crystal was loaded in advance. Growth of the seed crystal in a temperaturecontrolled environment (set at 23 °C) was monitored using an optical polarizing microscope (Olympus, BX51, equipped with a CCD camera) at a magnification of 4. The images of the growing seed crystal were acquired at regular time intervals using Analysis (Soft Imaging Systems) image capture software. The linear displacements along the c-axis and the b-axis of the acquired images of the seed crystal were measured, and they were plotted against time, respectively. The slope of the resulting linear plot (R2 > 0.99) gave the corresponding growth rate along a specified axis at the given supersaturation.
’ RESULTS AND DISCUSSION Growth Behavior at Low Supersaturations (σ e 1.75). At a supersaturation σ lower than 1.75, the typical growth behavior of a single needlelike DL-alanine crystal is shown in Figure 1, and the obtained growth rates are presented in Figure 2. To aid visualization, dotted vertical lines were drawn in Figure 1, delineating the +c and c ends of the seed crystal. It is found that the growth along the polar c-axis of a needlelike DL-alanine, representing the resulting growth of the faces at the polar c and +c ends, is too slow to be practically detectable (Figure 1). In contrast, the growth along the b-axis, representing the growth of the {210} side faces, is significant enough to be measurable (Figures 1 and 2) although not fast. 3942
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Figure 3. DL-Alanine crystals formed from a tion at supersaturation σ = 1.75.
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DL-alanine
aqueous solu-
Figure 5. Illustration of the unidirectional growth from the c end of a needlelike DL-alanine seed crystal at a supersaturation σ = 1.80.
Figure 4. Growth rates of DL-alanine, showing the growth along c-axis faster than that along b-axis at moderate (1.75 < σ e 1.90) and high (1.90 < σ e 2.20) supersaturations. The error bar is 20%. 1
As explained before, this unusually slow growth along the c-axis is an outcome of strong adsorption of the polar water molecules at the polar c ends. The preferentially adsorbed solvent water molecules at the faces at the polar ends not only block the active sites and hence prevent the solute DL-alanine molecules from their attachment but also make the local supersaturations at the associated faces lower than that of the bulk solution. Consequently, the growth of these faces is retarded, and a dead supersaturation zone exists with respect to the growth along the polar c-axis. Corresponding to such a growth behavior, the DL-alanine crystals grown from batch unseeded crystallization of a solution in a sealed vessel at 23 °C are not elongated along the c-axis and instead are prismatic pyramids (Figure 3), in agreement with our previous observation.1 It should be noted that it took a few days for these prismatic pyramids to appear and develop to a size of about 500 μm (Figure 3), reflecting the slow crystallization of DL-alanine at a low supersaturation. Growth Behavior at Moderate Supersaturations (1.75 < σ e 1.90). The growth behavior of DL-alanine crystal in a range of moderate supersaturations (1.75 < σ e 1.90) is depicted in Figure 4. For comparison (which will be discussed in next section), the growth rates at high supersaturations (σ > 1.90) are also presented in Figure 4. It is found that with the increase of supersaturation of the bulk solution from a low to a moderate level, the growth rate along the b-axis of a needlelike DL-alanine seed crystal, as usual, keeps increasing although very slowly. In contrast, the growth rate along the c-axis, virtually zero at supersaturation σ < 1.75,
Figure 6. Crystal packing of DL-alanine (built in Materials Studio27), showing the “ridges” and “pockets” and illustrating the different lone pair alanine water repulsions at the (001) face at the COO -rich c end and the (001) face at the NH3+-rich +c end. Solvent water molecules adsorbed within pockets are represented by the ball and stick notation. Color scale of atoms in packing: C (dark gray), N (blue), O (red), and H (white).
increases abruptly to become much faster than that along the b-axis (Figure 4). It should be pointed out that this fast growth along the c-axis at moderate supersaturations (1.75 < σ e 1.90) is dominantly determined by the growth from the c direction. In fact, the growth of the hemihedral faces at the pointed +c end remains practically undetectable, signifying a unidirectional growth (Figure 5), which was viewed9 as a typical growth behavior of DL-alanine. Given the significant growth acceleration from the c direction and no growth from the +c direction at σ > 1.75, it is indicated that the growth from the c end has a dead supersaturation zone of σ ≈ 1.75, while the growth from the +c end would have a larger one, which will be elaborated in next section. This unidirectional growth from the c direction was interpreted using a “relay” mechanism.9,17,26 In this mechanism, it was highlighted that the “ridges” and “pockets” at the rough COO rich (001) face at the flat c end play an important role in easing the desolvation step of crystal growth due to the weak binding of a water molecule adsorbed within a pocket. As explained,9 such a weak binding is because the two (alanine)O 3 3 3 H(water) attractive interactions within a pocket are counterbalanced by lone pair (alanine)O 3 3 3 O(water) repulsions, as illustrated in Figure 6. 3943
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Figure 8. (a) Rodlike DL-alanine crystals formed at a high supersaturation σ = 2.00. (b) Needlelike DL-alanine crystals formed at a moderate supersaturation σ = 1.90 at 23 °C.
Figure 7. Growth behavior and habit change of a DL-alanine crystal at a high supersaturation σ = 2.20, showing the shrinking and eventual disappearance of the relatively fast growing hemihedral {201} and {011} faces, appearance and development of the relatively slow growing (001) face, and subsequently the equal growth from the +c and the c directions.
In contrast, the hemihedral faces at the pointed +c end are comparatively smooth at the molecular level;9 hence, easing of desolvation is not expected at these smooth hemihedral faces. As a result, the rough (001) face at the flat c end grows faster than the smooth hemihedral faces at the pointed +c end. (The pockets and ridges at the (001) face emerging at the flat +c end at high supersaturations will be discussed in next section.) Growth Behavior at High Supersaturations (1.90 < σ e 2.20). The growth rates at these high supersaturations are presented in Figure 4. The most unexpected finding is that when the supersaturation σ of the bulk solution is further increased to a high level (σ > 1.90), the smooth hemihedral {201} and {011} faces at the pointed +c end start to grow fast and eventually grow out of existence, as illustrated in Figure 7. This observation also indicates that the growth of these hemihedral faces has a dead supersaturation zone of σ ≈ 1.90, larger than the dead supersaturation zone of σ ≈ 1.75 for the growth of the (001) face at the c end. With the vanishing of these hemihedral faces, the originally pointed +c end becomes flat (Figure 7b), showing the appearance of a new face at the +c end. This new face is perpendicular to the polar c-axis and hence symmetrically related to the (001) face at the c end, with its face index being (001). Such a growth behavior leads to a habit change of the seed crystal from pointed needlelike (Figure 7a) to rodlike (Figure 7b). After the new (001) face is well faceted, it starts to grow quickly, with a growth rate practically the same as that of the (001) face (Figure 7b,c). Thus, the growth along the c-axis at a high supersaturation is no longer unidirectional (Figure 7b,c), with both the c and the +c ends growing fast. In comparison, at a moderate supersaturation, only the c end grows while the +c end does not grow. As a result, the growth rate along the c-axis
undergoes a pronounced transition when the supersaturation progresses from a moderate to a high level, as indicated by the dotted line in Figure 4. Our experimental observation on batch unseeded crystallization of DL-alanine aqueous solutions adds further credence to the notion that the formation of rodlike DL-alanine crystals is more favored at a high supersaturation (e.g., σ = 2.00) (Figure 8a), while needlelike DL-alanine crystals with hemihedral faces at the pointed +c end form more readily at a moderate supersaturation (e.g., σ = 1.90) (Figure 8b). These new observations on the appearance, disappearance (or nonappearance), and unexpected fast growth of the faces at DL-alanine +c end (Figures 7 and 8) at high supersaturations may be explained on the basis of the “relay” mechanism9 and surface nucleation. Perusal of the packing structure of DL-alanine (Figure 6) reveals that the (001) face at the +c end exposes the amino (NH3+) groups. Similar to the (001) face at the c end, the (001) face is also relatively rough and contains “ridges” and “pockets”. It follows that, analogously, the “relay” mechanism9 may be applicable to the growth of the rough (001) face too, as a solvent water molecule can be adsorbed weakly within a pocket at the (001) face (Figure 6). Such a weak binding of water molecule is because the (alanine)NH3 3 3 3 O(water) attractive interactions are counterbalanced by lone pair (alanine)NH3 3 3 3 H(water) repulsions (Figure 6), resulting in easing of desolvation and hence fast growth of the (001) face. Thus, the “relay” mechanism9 could also rationalize the observation that, at moderate supersaturations (e.g., σ = 1.90), the rough (001) face, developing faster than these smooth hemihedral faces, grows out of existence, leading to a pointed +c end (Figure 8b). At a high supersaturation (σ > 1.90), however, it is not the case. In fact, at the +c end, the disappearance (Figure 7b) (or nonappearance, Figure 8a) of the hemihedral faces and the appearance (Figure 7c) of the (001) face suggest that these smooth hemihedral faces grow faster than the rough (001) face. Such an unexpected growth behavior, in contradiction of the explanation by the “relay” mechanism,9 is probably related to a change (or changes) in growth mechanism28 since surface nucleation (which is strongly supersaturation-dependent29) could become the dominant mechanism28,29 for crystal growth at high supersaturations. Furthermore, as pointed out,28 surface nucleation is particularly favored at the strained faces where the edges and corners (which are formed by the growth sector boundaries) emerge. It is possible that these hemihedral faces could be strained to a greater extent than the (001) face because of a larger difference in propagations of the adjacent dissimilar sectors (which are associated with the {210} side faces, (001) face and hemihedral faces themselves). 3944
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Figure 9. Identical PXRD patterns of DL-alanine crystals with different habits, showing that the crystalline structures of rodlike, needlelike, and prismatic DL-alanine crystals are the same.
The observed equal growth rates of the two {001} faces (Figure 7b,c), although associated with crystal attachment energy to a certain degree, would be partly attributed to the comparable enhancements of surface nucleation at these two faces at high supersaturations. This is because both of the {001} faces are likely to be strained similarly by the same pattern of four edges and four corners, which are formed by one of the {001} faces and the four {210} side faces (Figure 7c). Confirmation of DL-Alanine Solid Form. Our measured PXRD patterns (Figure 9) of the rodlike (Figure 8a), needlelike (Figure 8b), and prismatic (Figure 3) DL-alanine crystals, well comparable with the simulated PXRD pattern (CSD ref code DLALNI01), are practically identical. It is therefore shown that all of these DL-alanine crystals are the same in crystalline structure. This observation reascertains our previous conclusion1 that DL-alanine crystals grown from pure aqueous solutions have no difference in crystalline structure; hence, they are not polymorphs even if they exhibit different habits.
’ CONCLUSION We have systematically explored the effect of supersaturation on the face growth rates and hence revealed the precise habit modification of DL-alanine crystal. Our new experimental results show that with an increase of supersaturation σ to a moderate level, virtually no growth along the polar c-axis at low supersaturation becomes faster than that along the b-axis, with the growth from the c direction highly dominating the growth from the +c direction, demonstrating the phenomenon of unidirectional growth.9 With a further increase of supersaturation to a high level, the normally slow-growing hemihedral faces at the +c end develop exceptionally fast and eventually grow out of existence, leading to the fact that the growth along the polar c-axis is no longer unidirectional, which is the most unexpected growth behavior of the DL-alanine crystal. Such fast growth of these hemihedral faces, contrary to the postulation of the relay mechanism,9 is interpreted on the basis of surface nucleation. Largely corresponding to the supersaturation-dependent alteration of the face growth rates at the polar ends, the habit of DL-alanine crystal experiences a modification from prismatic, needlelike to rodlike. It would be interesting to further investigate whether the polar ends, especially the normally slow-growing polar end of other polar crystals, could exhibit a
similar growth behavior so as to provide new insights into crystal growth mechanisms.
’ AUTHOR INFORMATION Corresponding Author
*Tel: +65 6796-3879. Fax: +65 6316-6183. E-mail: han_guangjun@ ices.a-star.edu.sg (G.H.) or
[email protected] (R.B. H.T.).
’ ACKNOWLEDGMENT This work was financially supported by the Agency for Science, Technology and Research (A*STAR), Singapore. We thank Kuek Jia Wei Benjamin, Vijay Ramadoss, and Gloria Goh Karlyen for their assistance with the experiments. ’ REFERENCES (1) Han, G.; Poornachary, K. S.; Chow, P. S.; Tan, R. B. H. Cryst. Growth Des. 2010, 10, 4883–4889. (2) Curtin, D. Y.; Paul, I. C. Chem. Rev. 1981, 81, 525–541. (3) Park, J. W.; Hong, H.; Lee, K.; Yoon, C. S. Cryst. Growth Des. 2006, 6, 2011–2020. (4) Srinivasan, K.; Sherwood, J. N. Cryst. Growth Des. 2005, 5, 1350–1370. (5) Moolya, B. N.; Jayarama, A.; Sureshkumar, M. R.; Dharmaprakash, S. M. J. Cryst. Growth 2005, 280, 581–586. (6) Dhas, S. A. M. B.; Natarajan, S. Mater. Lett. 2008, 62, 2633–2636. (7) Anwar, J.; Chatchawalsaisin, J.; Kendrick, J. Angew.Chem., Int. Ed. 2007, 46, 5537–5540. (8) Hussain, M.; Anwar, J. J. Am. Chem. Soc. 1999, 121, 8583–8591. (9) Shimon, L. J. W.; Addadi, M.; Vaida, L.; Lahav, M.; Leiserowitz, L. J. Am. Chem. Soc. 1990, 112, 6215–6220. (10) Kubota, N. Cryst. Res. Technol. 2001, 36, 749–769. (11) Hod, I.; Mastai, Y.; Medina, D. D. CrystEngComm 2011, 13, 502–509. (12) Lahav, M.; Leiserowitz, L. Cryst. Growth Des. 2006, 6, 619–624. (13) Dowling, R.; Davey, R. J.; Curtis, R.; Han, G.; Poornachary, S. K.; Chow, P. S.; Tan, R. B. H. Chem. Commun. 2010, 46, 5924–5926. (14) Li, L.; Rodriguez-Hornedo, N. J. Cryst. Growth. 1992, 121, 33–38. (15) Towler, C. S.; Davey, R. J.; Lancaster, R. W.; Price, C. J. J. Am. Chem. Soc. 2004, 126, 13347–13353. (16) Yu, L. CrystEngComm 2007, 9, 847–851. (17) Weissbuch, I.; Torbeev, V. Y.; Leiserowitz, L.; Lahav, M. Angew. Chem., Int. Ed. 2005, 44, 3226–3229. 3945
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