Communication pubs.acs.org/crystal
Glycine’s pH-Dependent Polymorphism: A Perspective from SelfAssociation in Solution Weiwei Tang,† Huaping Mo,§ Mingtao Zhang,‡ Junbo Gong,*,† Jingkang Wang,† and Tonglei Li*,‡ †
School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin University, Tianjin 300072, People’s Republic of China ‡ Department of Industrial and Physical Pharmacy and §Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States S Supporting Information *
ABSTRACT: As a simple amino acid, glycine (Gly)’s polymorphism is pH-dependent. The α form is typically obtained from aqueous solution between pH of 4 and 9, while the γ is produced at either lower or higher pH. Formation of cyclic, hydrogen-bonded dimer in water is debated as a possible cause for the formation of the α form. To further understand the pHdependent polymorphism, our current study examined the self-association of Gly in aqueous solutions under a wide range of pH, utilizing NMR, FTIR, and electronic calculation. The results indicate that glycine molecules form open, not cyclic, hydrogen-bonded dimers in water. It is revealed that the dimerization becomes significant between pH of 4 and 8 but remains trivial at the two pH extremes. The apparent connection between the pH-dependent polymorphism and self-association in solution implies that formation of the α form is driven by the dimerization, and moreover, charged molecular species at the extreme pH facilitate stabilization of γ nuclei.
N
ucleation of organic molecules is a phase transition process where solute molecules engage in self-recognition and assembly, resulting in eventual formation of a particular crystal structure.1 Understanding solution chemistry thus becomes essential for comprehending the enigmatic nature of the nucleating process.2 Structural similarity between selfassemblies in solution and molecular synthons in the resultant crystal has shed light on possible mechanisms of nucleation.3−5 Such structural connection bridges solution chemistry and crystallization outcome, implying that nucleation proceeds from solution self-assemblies. Among these studies, solution chemistry of carbohydrates, including sugars and sugar alcohols, has been extensively examined,6 and it is found that the conformation distribution of solute molecules drastically affects the crystallization kinetics.7−11 A few other molecular systems are found that, when self-associated, form hydrogen-bonded dimers in particular solvents; only polymorphs with the dimer motif are crystallized. When no such dimers are present in other solvents, the crystallization only yields polymorphs bearing nondimer characteristics.12−15 Among others, one interesting debate in the literature is over the dimer formation of glycine in water.16−19 Our current study aims to further clarify the role of solution chemistry of glycine in its pHdependent polymorphism. Glycine (Gly), the smallest amino acid, is found to crystallize into at least three polymorphs with the phase stability order of γ > α > β under ambient conditions.20 Gly molecules become zwitterionic in all three polymorphs. The α form consists of centrosymmetrically arranged, hydrogen-bonded dimers (Figure 1a) and the other two forms adopt a polar arrangement.19 © XXXX American Chemical Society
Figure 1. (a) Gly cyclic (blue shade) and open (red shade) dimer motifs in the α form and (b) open dimer in the γ form.
The γ form bears helical hydrogen-bond chains with open, hydrogen-bonded dimers (Figure 1b).21 Nonetheless, the molecules in the α form can also be regarded as formation of additional types of hydrogen-bonding motifs, including the open dimer. In fact, each molecule forms the stronger (shorter and more linear) N−H···O hydrogen-bond chain with other molecules in the α form.20 The β form is least encountered and made of similar hydrogen-bond sheets as the α form but with chain, not cyclic dimer, hydrogen-bonded motifs. Interestingly, the polymorphism is known to be affected by pH of the crystallization media and the metastable α form always crystallizes in the pH range from 3.8 to 8.9, whereas the γ form may be obtained under sufficiently acidic (pH < 3.8) or basic conditions (pH > 8.9).22,23 It is noted that at even more acidic conditions (e.g., pH = 2.0) glycine HCl salts (i.e., glycine Received: July 12, 2017 Revised: August 31, 2017 Published: September 11, 2017 A
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HCl and diglycine HCl) can be formed.23 Gly has been studied extensively and it is often debated in the literature about whether it forms the cyclic, hydrogen-bonded dimer in water that leads to the selective crystallization of the α form.16,19,24 Different amounts of dimers, ranging from 5% to 30% (mole fraction), are detected in water by different experimental methods, including freezing-point depression,19 diffusivity,19,20 dielectric relaxation,25 and ultracentrifugation.26 Nonetheless, there seems to be no report exploring the pH effects on the self-association at various concentrations, which could help understanding the pH-dependent polymorphism of glycine. Moreover, possible structures of the solution dimer have not been further characterized experimentally. Computational studies, on the other hand, have probed various dimer structures, but the stability or energy ranking of dimer species remains inconsistent by different computation methods. A quantum mechanical study suggested that the double hydrogen-bonded, cyclic dimer is more stable than the open one,27 whereas molecular dynamic simulations showed that open dimers are more dominant.21,28 A recent report postulated that long head-to-tail chains of neutral-zwitterion associates via ion− dipole interaction could be formed under acidic or basic conditions.29 As indicated by our current study, such a possibility seems to be remote. Herein, we examine the solution chemistry of Gly in water under different pH and concentration conditions to seek understanding of the pHdependent polymorph formation. Because of the carboxyl and amino groups, Gly can ionize into various forms in water, including cation (Gly+), zwitterion (Gly±), and anion (Gly−), as shown in Figure 2a. The ionization is pH-dependent and Figure 2b illustrates the quantitative relationships among the charged species as functions of pH in H2O and of pD in D2O. The reported
ionization constants of 2.35 (carboxyl) and 9.78 (amino) of H2O30 and 2.82 and 10.59 of D2O31 are used for the calculation. The neutral form is insignificant compared with other forms.32 In addition, pure Gly aqueous solutions (H2O or D2O) of various concentrations have pH or pD values of 6−8 (Figure S1). It is thus expected that Gly mainly remains zwitterionic in water and the Gly± may self-associate into hydrogen-bonded dimers ((Gly±)2). Identification of such dimers and their configurations is the main thrust of this report. Importantly, pH-dependent dimerization has been explored experimentally and possible linkage with the pHdependent polymorphism is speculated in our current study. IR spectra were collected of the α and γ forms, as well as solutions of a series of concentrations (Figure 3). The solid-
Figure 3. Concentration-dependent IR spectra of Gly in H2O and solid-state spectra of α and γ forms. The vertical solid line is used to highlight the shifts of −COO− and −NH3+ peaks.
state IR spectrum of the γ form shows a strong band of carboxylate (−COO−) asymmetric stretching at 1572 cm−1 and a doublet peak of ammonium (−NH3+) bending at 1491 and 1477 cm−1. The −COO− stretching in the α form locates at 1581 cm−1 and the −NH3+ bending at 1501 cm−1. The shoulder peaks of the −COO− band in either form result from the overlay of −NH3+ asymmetric bending.33,34 Both −COO− and −NH3+ bands of Gly solutions reveal significant red shifts with the increase of concentration, respectively, from 1606 to 1590 cm−1 and from 1513 to 1504 cm−1 toward the solid-state values. The concentration-dependent spectral shifts indicate intermolecular interactions between solute molecules, likely through formation of the −COO···H−N− hydrogen bond. The two IR bands, however, are too broad to identify possible Gly species. 1 H and 13C chemical shifts of Gly solution were measured as a function of concentration and shown in Figure 4. Both methylene (CH2) protons and carboxylate carbon display similar concentration-dependent trends in D2O. The initial deshielding of CH2 protons at low concentrations is believed to be mainly caused by shifting in the ionization equilibrium toward Gly−. This is because larger pH is found at the low concentration (Figure S1 and Figure 2b); for example, pH > 7.5 and 6.7 in pure D2O and 5% D2O, respectively, when the
Figure 2. (a) Ionization and dimerization equilibria of Gly in aqueous solution and (b) solution speciation of 2.88 M glycine (saturated) in aqueous solution as functions of pH and pD. Solid lines are of H2O and dashed of D2O. The dimerization of (Gly±)2 is derived with the experimentally determined Kd, 0.044 M−1, by chemical shift measurements discussed later in the text. B
DOI: 10.1021/acs.cgd.7b00969 Cryst. Growth Des. XXXX, XXX, XXX−XXX
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C0 = [Gly +] + [Gly −] + [Gly ±] + 2Kd[Gly ±]2
(2)
[Gly +] = 10(pKa1‐ pH)[Gly ±]
(3)
[Gly −] = 10(pH − pKa 2)[Gly ±]
(4)
in which δx is chemical shift of the species x (Gly , Gly , Gly±, or (Gly±)2), C0 is total concentration of Gly, Kd is dimerization constant, and pKa1 and pKa2 are ionization constants of carboxyl and amino groups, respectively. The fitting, shown in Figure 4 as the solid lines, yields dimerization constant Kd of 0.039 ± 0.011 and 0.048 ± 0.016 M−1 from the 1H chemical shift values in D2O and 95% H2O/D2O, respectively. The similar dimerization constants in both D2O and 95% H2O/D2O confirm no significant impact on the Gly self-association by deuteration of H2O. With the obtained Kd, the dimer fraction in water can be derived as 16−19% of 2.88 M Gly (solubility of the α form19). Note that the average value of Kd (0.044 M−1) in water was utilized for the calculations in Figure 2b. It is in good agreement with 18% dimer fraction reported from the freezingpoint depression measurement at 298 K19 and 20−25% (3.6 M) at 293 K from the molecular dynamic simulation.20 Fitting of the ionization equilibria and dimerization model to the 13C chemical shifts using the derived Kd from 1H measurements yields changes in −COO−13C chemical shift from the monomeric (δGly±) to dimeric species (δ(Gly±)2) as 0.55 and 0.46 ppm in D2O and 95% H2O/D2O, respectively. Intermolecular contacts of Gly in D2O were investigated by 2D NOESY. The methylene 12C and 13C protons of natural abundance were probed for possible contacts between solute molecules in solution. Measuring over the two isotopes ensures that the same protons from two different molecules could be determined. Figure 5a illustrates close contacts between +
Figure 4. Chemical shifts of Gly methylene 1H (a) and carboxylate 13C (b) in D2O and 95% v/v H2O/D2O. The solid-lines represent the best fit using eqs 1−4.
concentration is smaller than 0.1 M. The deshielding of carboxylate 13C resonance upon ionization, as observed in Figure 4b when the concentration is diluted, is well documented in the literature.35,36 As the solute concentration increases, pH starts to decrease (Figure S1) and the subsequent downfield shifts in both 1H and 13C most likely arise out of the Gly self-association, in agreement with what the IR data suggests. The downfield change of the carboxylate 13C chemical shift stems from strong electron affinity by the ammonium group, likely due to the formation of intermolecular −COO··· H−N− hydrogen bond. The literature reports argue that deuteration of H2O may affect intermolecular interaction between solutes in solution.37,38 As such, we also measured chemical shifts in H2O with 5% D2O (volume fraction) locking magnetic field (Figure 4). The overall trends in CH2 1H and −COO− 13C chemical shifts are similar and deuteration of H2O does not appear to have a major influence on the Gly selfassociation. The difference in the absolute values of chemical shifts in H2O and D2O is mainly an effect of isotopic substitution of Gly by solvent D2O. The observed 1H and 13C chemical shifts are ensemble averages of various solution species. According to the ionization equilibria (Figure 2a) and dimerization model, the experimental data is fitted by the following equations: δobs
Figure 5. (a) 2D NOESY plot of 3.0 M glycine in D2O with positive and negative signals represented by blue and red contours, respectively. (b) Interproton contact between 12C and 13C methylene protons of an open hydrogen-bonded dimer. Location of possible NOE of the contact is highlighted by yellow arrows in (a).
methylene protons of 12C and 13C resonances. For a small molecule such as Gly, the positive enhancement of NOE crosspeaks generally leads to the opposite phase along the diagonal, mainly due to cross-relaxation of double quantum transition between spins. If Gly forms self-associates with short interproton distances (Figure 5b), observation of related
[Gly +] [Gly −] [Gly ±] = δGly + + δGly − + δGly ± C0 C0 C0 + δ(Gly±)2
2Kd[Gly ±]2 C0
−
(1) C
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titrating solution, or the ionic strength effect, on the proton chemical shifts. This is confirmed by conducting the same titration experiment at 5.0 × 10−3 M with the salt concentration fixed at 1.4 or 2.7 M. Similarly large deviations are found at pH below 3 and above 9 (Figure S2). Moreover, CH2 proton chemical shifts were measured at constant pH but with the salt concentration varied. The chemical shift shows linear downfield changes as a function of the salt concentration (Figure S3). The measurement reveals that the salt effect on the chemical shifts observed in Figure 6 is no greater than 0.02 ppm in the pH range of 4−8, where the salt concentration is at 1.4 M. Within this pH range, the change in chemical shift due to selfassociation is about 0.018 ppm, comparable with 0.017 ppm calculated from the dimerization model (blue dashed line in Figure 6). In all, the results support the claim of self-association by Gly when the solution is mainly neutral. Under acidic or basic condition, the self-association becomes trivial. To further investigate the likely configuration of hydrogenbonded dimers in solution, binding or intermolecular interaction energies of all possible hydrogen-bonded dimer motifs found in α and γ forms were evaluated. Results are shown in Figure 7. Per hydrogen bond, the open dimers are
NOE signals is expected. Nevertheless, no NOE was found in the locations (pointed by yellow arrows in Figure 5a), suggesting that the interproton distance should not be less than 4−5 Å because of the r−6 dependence of NOE on the interproton distance (r). Note that the observed cross-peaks of the same positive phase as the diagonal come from spin coupling and belong to the two protons of the same 13C, rather than the intermolecular contact of two different Gly molecules. To study the effect of pH on solution speciation and selfassociation of Gly in water, NMR titration experiments were performed. Because the chemical shift of CH2 protons is very sensitive to its local environment, deshielding of 1H resonance is utilized to probe self-association at different pH. Figure 6
Figure 6. 1H chemical shift measurement of methylene protons at two extreme concentrations of aqueous Gly solution as a function of pH. The line at 5.0 × 10−3 M is the best fit to a two-step ionization equilibria model. The blue dashed line represents the derived chemical shift difference at the ideal case of Gly self-association. The labeled bar presents the pH-dependent crystallization outcomes of Gly polymorphs.
shows experimental results of methylene proton chemical shifts at two extreme concentrations (black data points). Of the same concentration, the chemical shift shows little change over pH range 4−8, but shifting toward ionized species, cationic or anionic, outside the pH range (as seen in Figure 2b) causes significant changes. When no self-association is assumed for the lower concentration (5.0 × 10−3 M), fitting the chemical shift data by eqs 1−4 produces two ionization constants (pKa) of 2.33 ± 0.04 and 9.65 ± 0.04, matched well with 2.35 and 9.78 reported in the literature.30 Furthermore, the change in chemical shift from 5.0 × 10−3 to 2.7 M (blue points in Figure 6), which is within the solubility of 2.6−2.8 M dependent upon the solution pH,39 illustrates significant downfield variations in the pH range from 4 to 8. The downfield changes become much smaller at lower and higher pH. Based on the dimerization model and pH-dependent ionization equilibria (eqs 1−4), as well as the derived chemical shifts of related species, the theoretical difference in chemical shift between the two concentrations is calculated and plotted as the dashed blue line in Figure 6. The similarity between the experimental and computed downfield changes supports the Gly’s self-association between pH 4 and 8, which rapidly vanishes when pH reduces to 2 or increases to 10. The deviations from the computed profile at pH below 3 and above 9 actually result from the presence of salt (1.4 to 2.7 M) in the
Figure 7. Optimized dimer geometries, calculated binding energies (ΔEbind), carboxylate 13C chemical shift changes (Δδ) from monomeric to dimeric states, and the shortest interproton distance between methylene protons (d) in the dimer.
stronger by about 3−7 kJ·mol−1 than the cyclic dimers. Solvation of Gly by H2O, mainly through hydrogen bonding, can further stabilize the open dimers. Conversely, formation of the additional hydrogen bond by a cyclic dimer is at the expense of two bounded water molecules, leading to decrease in the binding energy by about 2−6 kJ·mol−1. The similar D
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inorganic bases (NaOH, KOH) and acids (HCl, HNO3, and H2SO4) as additives enhances, rather than inhibits, the growth of both forms.42 It is discovered that many inorganic salts can significantly shorten the induction time of the γ form.43 The γ form may also be obtained from pure water by adjusting the polarization state of an applied laser beam,44 or by applying a strong electric field.45 Based on the significant difference in the solution chemistry between neutral and acidic/basic solutions that is discovered in our study, alignment of solution species of glycine, dimer or monomer, could be the deterministic factor for the pH-dependent polymorphism, rather than the difference in growth rate of nuclei and/or crystallites. In summary, our study found that Gly self-associates in water and deuteration of H2O levels little effect on the degree of selfassociation. The self-assembly is believed to be open, not cyclic, hydrogen-bonded. Moreover, between pH of 4 and 8, the dimerization is mostly significant but becomes trivial beyond the pH range. Given the concurrent pH-dependent selfassociation and polymorphism, it is speculated that the dimerization leads to clustering of the open dimer species that transform into cyclic hydrogen-bonded motifs and eventual α nuclei. The monomeric zwitterions, on the other hand, are facilitated by charged molecules in the solution into nucleating the polar, γ nuclei. While more studies are indeed needed to better understand the evolution of open dimers in the clusters and the noncentrosymmetric tessellation of monomers in an ionic environment, this study undoubtedly unveils the importance of solution speciation in determining the nucleation outcome of glycine.
interaction energies among all open dimers suggest their interconversion in solution. In addition to the energy calculation, experimentally derived values of −COO−13C chemical shift fall within the calculated range of open dimers (Figure 7) which have a wider range from 0.03 to 1.79 ppm but consistently smaller than those of the cyclic dimers (1.83−2.23 ppm). Solid-state 13C NMR data show that the carboxylate 13C resonance is 176.5 ppm in α form, higher by 2.0 ppm than that of γ form.40 Because of extreme sensitivity of chemical shift to its local environment, the 13C chemical shift difference in the two forms corroborates the stronger deshielding of −COO−13C resonance in the cyclic dimer than the open one. Our calculation of chemical shifts of the dimer motifs found in the α and γ forms (Table S1) indicates that the cyclic dimer bears about 5 ppm on average higher than the open motif in the α form and those in the γ. The average chemical shift of open dimers in the two forms is nearly identical. Our calculated 13C chemical shift in the α form is larger by 2.8 ppm than that of γ form. Jointly, these data support that Gly dimers in solution are mainly of open, hydrogen-bonded configuration. NOE of methylene 12C and 13 C protons was intended to differentiate open dimers and reveals that the interproton distances of methylene protons in the hydrogen-bonded associates is at least 4 Å. All optimized open, hydrogen-bonded dimers except dimer G (Figure 7), nonetheless, have the interproton distance above 4 Å. Given their similar binding energies, all the open motifs are believed to be in fast equilibria with each other in the solution. As highlighted in Figure 6, the Gly’s α form is generally nucleated and crystallized in the pH range of 3.8−8.9 (±0.25), whereas the more stable γ form can be obtained either below or above the range.22,23 The apparent connection between the pH-dependent polymorph formation and the self-association of the solute makes it tempting to speculate on the nucleation mechanism. Our chemical shift and IR measurements, as well as energy and chemical shift calculations, suggest that Gly forms hydrogen-bonded dimers that are open rather than cyclic in water. The finding is echoed by the NOE study and the NMR titration experiments. Ostensible discrepancy seems to exist. The α form can be regarded as tessellation of the cyclic dimers, but the solution in which the α nucleates mainly contains open dimers (in addition to the dominant monomeric species). If the solution speciation is the leading cause for the nucleation of the α form, not the γ, we could argue that formation of the cyclic dimer results from the clustering of the open dimers and subsequent reorganization of intermolecular interactions that favor stronger internal energies among the same molecules. Arguably, despite the γ form being more stable, the open dimer motifs in the solution kinetically lead to the eventual creation of the cyclic motif. On the other hand, formation of the γ form may be facilitated by charged molecules formed under acidic or basic solution conditions, which seem to discourage formation of hydrogenbonded dimers. If such an assumption holds, single solute molecules, rather than dimeric species, may be better aligned by the charged milieu in forming stable nuclei. Nonetheless, further experimental studies are needed to explore the pHdependent nucleation mechanism. Moreover, it has been suggested in the literature that growth kinetics of nuclei may be responsible for obtaining a particular polymorph under specific conditions.41 However, a recent study revealed that the growth rate of the α form is merely 1.6 times of that of the γ form.42 Furthermore, it is found that using
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.cgd.7b00969. Experimental and computational section, solution pH vs concentration of Gly, salt effect on proton chemical shifts, and NMR chemical shift calculations (PDF)
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Junbo Gong: 0000-0002-3376-3296 Tonglei Li: 0000-0003-2491-0263 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS W.W. acknowledges funding support from the China Scholarship Council (CSC), and J.B. thanks the National Natural Science Foundation of China (NSFC; No. 21676179 and No. 91634117) for financially supporting the research. T.L. thanks Chao Endowment for supporting the research.
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REFERENCES
(1) Mattei, A.; Mei, X.; Miller, A. F.; Li, T. Cryst. Growth Des. 2013, 13, 3303. (2) Davey, R. J.; Schroeder, S. L.; ter Horst, J. H. Angew. Chem., Int. Ed. 2013, 52, 2166. (3) Davey, R.; Dent, G.; Mughal, R.; Parveen, S. Cryst. Growth Des. 2006, 6, 1788.
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(44) Garetz, B. A.; Matic, J.; Myerson, A. S. Phys. Rev. Lett. 2002, 89, 175501. (45) Aber, J. E.; Arnold, S.; Garetz, B. A.; Myerson, A. S. Phys. Rev. Lett. 2005, 94, 145503.
(4) Spitaleri, A.; Hunter, C. A.; McCabe, J. F.; Packer, M. J.; Cockroft, S. L. CrystEngComm 2004, 6, 489. (5) Hunter, C. A.; McCabe, J. F.; Spitaleri, A. CrystEngComm 2012, 14, 7115. (6) Jeffrey, G. Acta Crystallogr., Sect. B: Struct. Sci. 1990, 46, 89. (7) Bensouissi, A.; Roge, B.; Mathlouthi, M. Food Chem. 2010, 122, 443. (8) Jabrane, S.; Letoffe, J. M.; Claudy, P. Thermochim. Acta 1995, 258, 33. (9) Jeffrey, G. A.; Kim, H. S. Carbohydr. Res. 1970, 14, 207. (10) Schouten, A.; Kanters, J. A.; Kroon, J.; Comini, S.; Looten, P.; Mathlouthi, M. Carbohydr. Res. 1998, 312, 131. (11) Siniti, M.; Jabrane, S.; Letoffe, J. M. Thermochim. Acta 1999, 325, 171. (12) Davey, R.; Blagden, N.; Righini, S.; Alison, H.; Quayle, M.; Fuller, S. Cryst. Growth Des. 2001, 1, 59. (13) Parveen, S.; Davey, R. J.; Dent, G.; Pritchard, R. G. Chem. Commun. 2005, 1531. (14) Hamad, S.; Moon, C.; Catlow, C. R. A.; Hulme, A. T.; Price, S. L. J. Phys. Chem. B 2006, 110, 3323. (15) Chen, J.; Trout, B. L. J. Phys. Chem. B 2008, 112, 7794. (16) Gidalevitz, D.; Feidenhans’l, R.; Matlis, S.; Smilgies, D.-M.; Christensen, M. J.; Leiserowitz, L. Angew. Chem., Int. Ed. Engl. 1997, 36, 955. (17) Myerson, A. S.; Lo, P. Y. J. Cryst. Growth 1990, 99, 1048. (18) Erdemir, D.; Chattopadhyay, S.; Guo, L.; Ilavsky, J.; Amenitsch, H.; Segre, C. U.; Myerson, A. S. Phys. Rev. Lett. 2007, 99, 115702. (19) Huang, J.; Stringfellow, T. C.; Yu, L. J. Am. Chem. Soc. 2008, 130, 13973. (20) Hughes, C. E.; Hamad, S.; Harris, K. D. M.; Catlow, C. R. A.; Griffiths, P. C. Faraday Discuss. 2007, 136, 71. (21) Yani, Y.; Chow, P. S.; Tan, R. B. H. Cryst. Growth Des. 2012, 12, 4771. (22) Towler, C. S.; Davey, R. J.; Lancaster, R. W.; Price, C. J. J. Am. Chem. Soc. 2004, 126, 13347. (23) Yu, L.; Ng, K. J. Pharm. Sci. 2002, 91, 2367. (24) Chattopadhyay, S.; Erdemir, D.; Evans, J. M. B.; Ilavsky, J.; Amenitsch, H.; Segre, C. U.; Myerson, A. S. Cryst. Growth Des. 2005, 5, 523. (25) Sato, T.; Buchner, R.; Fernandez, Š.; Chiba, A.; Kunz, W. J. Mol. Liq. 2005, 117, 93. (26) Kellermeier, M.; Rosenberg, R.; Moise, A.; Anders, U.; Przybylski, M.; Colfen, H. Faraday Discuss. 2012, 159, 23. (27) Friant-Michel, P.; Ruiz-López, M. F. ChemPhysChem 2010, 11, 3499. (28) Hamad, S.; Hughes, C. E.; Catlow, C. R. A.; Harris, K. D. M. J. Phys. Chem. B 2008, 112, 7280. (29) Han, G.; Thirunahari, S.; Shan Chow, P.; Tan, R. B. H. CrystEngComm 2013, 15, 1218. (30) King, E. J. J. Am. Chem. Soc. 1951, 73, 155. (31) Stephen Reid, R.; Podányi, B. J. Inorg. Biochem. 1988, 32, 183. (32) Darvey, I. G. Biochem. Educ. 1995, 23, 141. (33) Rosado, M. T.; Duarte, M. L. T. S.; Fausto, R. Vib. Spectrosc. 1998, 16, 35. (34) Baran, J.; Ratajczak, H. Spectrochim. Acta, Part A 2005, 61, 1611. (35) Hagen, R.; Roberts, J. D. J. Am. Chem. Soc. 1969, 91, 4504. (36) Holmes, D. L.; Lightner, D. A. Tetrahedron 1996, 52, 5319. (37) Hughes, C. E.; Harris, K. D. M. New J. Chem. 2009, 33, 713. (38) Iitaka, Y. Acta Crystallogr. 1961, 14, 1. (39) Carta, R.; Tola, G. J. Chem. Eng. Data 1996, 41, 414. (40) Harris, K. D. M.; Hughes, C. E.; Williams, P. A. Solid State Nucl. Magn. Reson. 2015, 65, 107. (41) Chew, J. W.; Black, S. N.; Chow, P. S.; Tan, R. B. H.; Carpenter, K. J. CrystEngComm 2007, 9, 128. (42) Han, G.; Chow, P. S.; Tan, R. B. H. Cryst. Growth Des. 2012, 12, 2213. (43) Han, G.; Chow, P. S.; Tan, R. B. H. Cryst. Growth Des. 2016, 16, 6499. F
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