Article pubs.acs.org/crystal
Experimental Evaluation of Contact Secondary Nucleation Mechanisms Yuqing Cui and Allan S. Myerson* Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States S Supporting Information *
ABSTRACT: Contact secondary nucleation has vital importance in industrial crystallizers for reactions and purification, and it recently has been linked to contributing to biological homochirality emerged at an abiotic evolutionary stage. Despite years of studies, the mechanism of contact secondary nucleation has not been resolved whether contact secondary nuclei originate from parent crystals via microattrition or from semiordered solute clusters at the interface of parent crystals. This study takes advantage of the unique thermodynamic and kinetic properties of the glycine system that is capable of differentiating the origin of contact secondary nuclei based on the polymorph of secondary nuclei obtained. It is demonstrated using two different experimental designs that contact secondary nuclei could originate both from the semiordered solute molecules at the interface layer of existing crystals and from parent crystals themselves via the mechanism of microattrition depending on the magnitude of the contact force. When the contact force is relatively small (2 N for γ-glycine), it not only disturbs the interface layer but also causes mechanical damages to the parent crystals.
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INTRODUCTION Contact secondary nucleation, the generation of nuclei due to contacts of an existing parent crystal, has long been studied due to its prevalence and importance in industrial crystallizers for reactions and purification.1,2 In recent years, contact secondary nucleation has manifested new vital importance in some processes of great interest to the scientific community. For example, contact secondary nucleation is now considered to be the single most important nucleation mechanism leading to biological homochirality emerged at an abiotic evolutionary stage. As various studies have demonstrated, once the mirrorsymmetry of a chiral crystal is broken, contact secondary nucleation plays a critical role in the autocatalysis of one of the handedness that eventually leads to complete homochirality.3−7 The same principle has also been applied for enantiomer selection in certain processes.8,9 Given such importance of contact secondary nucleation and the fact that it has been studied since the 1950s,10 it is curious that the exact mechanism of contact secondary nucleation has not been fully resolved. It is generally believed that contact secondary nucleation is no more than microattrition taking place at the surface of a parent crystal. This theory is supported by a number of experimental observations. Tai et al.11 and Johnson et al.12 discovered that the ease of abrasion of the crystal surface appears to influence secondary nucleation characteristics, which suggest a microattrition mechanism. This theory is strengthened by Denk and Botsaris’ experiments13 where a parent crystal of one sodium chlorate © 2014 American Chemical Society
enantiomer was suspended in a slightly supersaturated solution. When contacted by a stainless steel striker, almost all the nuclei were of the same enantiomer form as the parent crystal independent of liquid velocity, while at a higher supersaturation where primary nucleation occurs, sodium chlorate solution should crystallize into crystals of 50% of each enantiomer.14 This microattrition theory is also confirmed by isotopic labeling of crystals.15 Shimizu et al. prepared a K-alum parent crystal containing D2O, and contacted it with a glass rod in a supersaturated K-alum H2O solution. The secondary nuclei generated by contact have a much greater content of deuterium than those generated by initial breeding, fluid shear, or control experiments. In 1978, the microattrition event that was believed to take place in contact nucleation was directly observed by Garside and Larson.16 A unique experimental design was used to allow direct microscopic observation of a potash alum parent crystal before and after contact in a supersaturated solution. Fragments (secondary nuclei ranging from 1 to 15 μm) from the crystal in the vicinity of the contact were observed. The surface of the parent crystal where contact took place was damaged immediately after the contact and healed over time because of crystal growth in supersaturated solution. Many other studies also observed microscopic damages to the parent crystal after contact in situ2,17 and ex situ.18 Interestingly, it has Received: June 13, 2014 Revised: August 13, 2014 Published: August 20, 2014 5152
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also been found that contact secondary nucleation seem to be related to macro-steps of the parent crystal2 and that a contact may induce new screw dislocation for growth on parent crystals.17 There is another theory that suggests contact secondary nuclei, instead of coming directly from the parent crystal, actually originate from semiordered clusters of solute molecules at the interface layer on the surface of parent crystals. Such an interface layer is several microns thick and its existence around growing crystals in a supersaturated solution has been confirmed experimentally.19 While many studies supporting this theory are theoretical,10,20 there are experimental studies that suggest such a mechanism as well: Friej et al. observed no visible damage to the surface of an potash alum parent crystal under atomic force microscope before and after a gentle contact of a glass slide, and yet secondary nuclei were generated during the process;21 Reyhani and Parkinson took advantage of the fact that chrome alum and potash alum crystals are isomorphous and found that after a gentle contact with the chrome alum parent crystal in potash alum solution using a 200 mesh copper grid coated with carbon film, secondary nuclei were generated, but the energy dispersive X-ray analysis of these secondary nuclei revealed no trace of chromium.22 This indicates there was no transfer of solid to the new crystals and thus showed the interface layer was the most probable source of contact secondary nuclei. When examining these studies, one can make an interesting observation that all experiments where damages to the seed crystal were not observed had relatively small contact forces: a “gentle contact”.21,22 In the experiments where microattrition was observed, the contact forces were larger in magnitude and usually came from a glass/stainless steel rod dropped from a certain height.11−13,16,17 It is therefore logical to hypothesize that the source of secondary nuclei could come from both sources proposed in literature depending on the magnitude of the contact force, i.e., when the contact force is relatively small, it is only sufficient to disturb the semiordered solute molecules in the interface layer, which generates secondary nuclei; when the contact force exceeds a certain threshold, it not only disturbs the interface layer but also causes mechanical damages to the seed crystal. One possible reason why the microattrition theory and the interface layer theory still have not been resolved after so many decades is the fact that nuclei coming from parent crystals and solution are difficult to distinguish in practice. Thus, a system where nuclei show its origin of birth is needed. The glycine− water system satisfies this requirement: at ambient conditions without the presence of additives, the α form is kinetically favored, and therefore, nucleation from aqueous glycine solution at ambient conditions only generates the α form. However, microattrition can only yield nuclei of the same polymorph as the parent crystal. Thus, if the parent crystal is γglycine, the appearance of the α form of secondary nuclei would indicate they originate from the interface layer, while the γ form would suggest microattrition takes place. In addition, the γ form has the lowest free energy (or solubility) at ambient conditions and is the thermodynamically most stable polymorph.23 Therefore, the α-glycine crystals could not have been produced due to the transformation from the γ form. The goal of this study is to take advantage of this unique feature of the glycine system and determine the source where contact secondary nuclei are generated.
Article
EXPERIMENTAL SECTION
Materials. Glycine (99%) was purchased from Alfa Aesar. Ultrapure water (resistivity 18.2 MΩ cm at 25 °C) was used as solvent in this study. γ-Glycine single crystals were obtained using two protocols previous described.24,25 The γ-glycine seed crystals used in the stirred batch experiment were large single crystals. The seed crystals used in the contact secondary nucleation experiments were selected to have contact areas (i.e., the 2-D surface area of the crystal face being contacted, see Supporting Information) between 5.0 mm2 and 18.5 mm2. All area measurements were carried out in ImageJ. Contact Secondary Nucleation Experiment. A glycine solution with a concentration of 230 g glycine/kg water was prepared, stirred at 55 °C overnight to ensure solids fully dissolve, and double filtered with Whatman quantitative filter paper (ashless, grade 40). Twenty-five milliliters of such solution was distributed into each of the two jacketed beakers prewarmed to 28 °C. The temperature of the solution was allowed to equilibrate with that of the jacketed beaker. A γ-glycine single crystal was attached, using minimal 2-part epoxy, to one end of a stainless steel rod such that the crystalline plane of interest, (100), (101), (102), or their symmetry planes, were exposed and perpendicular to the rod. The parent crystal was washed in solvent to etch the crystal surface and to prevent initial breeding before being placed in the aforementioned solution. The parent crystal was suspended in this undersaturated solution (see ref 26 for solubility of glycine in water) as shown in the experiment setup “Before Contact” in Figure 1 for 20 min before the temperature of the solution was cooled to 18.5 °C at 1 °C/min.
Figure 1. Experimental setup. The parent crystal was suspended in the supersaturated solution (supersaturation 1.34 with respect to γ-glycine and 1.19 with respect to α-glycine) at 18.5 °C for 60 min. The suspended rod was then released from a certain height Δh and the crystal face of interest came in contact with the bottom of the glass beaker. The height where the crystal was released from was related to contact force by calibration with a force gauge (see Supporting Information for calibration curve). The parent crystal and rod were then removed from the solution, which was cooled to 16 °C at 1 °C/min to allow contact secondary nuclei to grow. These grown nuclei were filtered and dried after 20 h of growth, and their polymorph was determined using Kaiser Raman microscope by comparing to reference spectra.27 Control experiments were carried out where the protocol was identical to that described above except that the parent γ-glycine crystal was replaced with half of a glass bead. The cross sectional surface being contacted has comparable area to a crystalline plane of the γ-glycine parent crystal. The contact area of the glass bead was measured to be 18.68 mm2. One experiment was conducted at a contact force of 1.7 N, 4 at 2.2 N, 2 at 2.5 N, and 10 at 2.7 N. The contact force range covers that of the experiments with glycine parent crystals. None of the control experiments resulted in any nucleation, eliminating the possibility of primary nucleation and heterogeneous nucleation. Stirred Batch Crystallizer Experiment. A glycine solution with a concentration of 230 g glycine/kg water was prepared, stirred at 55 °C overnight to ensure solids fully dissolve. Twenty milliliters of this solution was filtered and transferred into a 50 mL jacketed beaker 5153
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Crystal Growth & Design
Article
prewarmed to 28 °C. The temperature of the solution was allowed to equilibrate with that of the jacketed beaker. Then, 1.0 ± 0.1 g of γglycine single crystals were added into the beaker after being washed in solvent to prevent initial breeding. The solution was then cooled to 18.5 °C at 1 °C/min. After the solution reached the set point temperature, the agitator was turned on and the stir rate was set to 100, 150, 200, 300, or 500 rpm. The solution and parent crystals were stirred for 2.5 h with a two-blade MultiMax (Mettler Toledo) propeller made of stainless steel. Contact secondary nucleation clearly took place during the experiment as many fine crystals became visible. In one set of experiments, samples were taken right after the agitation stopped, where all the fine crystals generated by secondary nucleation were filtered via vacuum filtration, dried, weighed, and analyzed with powder X-ray diffraction (PXRD). In a second set of experiments, the contact secondary nuclei were allowed to grow for another 20 h at 16 °C without agitation before the crystals were analyzed with the same procedure as in the first set of experiments. The polymorph content of fine crystals generated by contact secondary nucleation was determined using PXRD (see Supporting Information for methods and calibration). Two control experiments were performed: in the first control experiment, the parent single crystals were replaced with 1.0 g of glass beads 5 mm in diameter. Under the same experimental conditions as described before, no crystals were observed immediately after stirring or after another 20 h of waiting at 16 °C, ruling out the possibility of primary nucleation from solution, heterogeneous nucleation on crystallizer walls, and fluid shear. The second control experiment had the same solution and parent crystals, but the parent crystals remained unstirred for 2.5 h at 18.5 °C before being held in the solution at 16 °C for 20 h. In this control experiment, no α-glycine crystals were found to grow either in solution or on the surface of the γ parent crystals, ruling out the possibility of epitaxial growth of αglycine on top of the γ form.
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RESULTS AND DISCUSSION Contact Secondary Nucleation Experiment. The result of contact secondary nucleation, shown in Figure 2, varied depending on the magnitude of contact force. The black bars in Figure 2 represent the probability that no contact secondary nucleation occurred. At low forces (
