Leapfrogging Ostwald’s Rule of Stages: Crystallization of Stable γ-Glycine Directly from Microemulsions

Chen, Cen; Cook, Oliver; Nicholson, Catherine; Cooper, Sharon J.

doi:10.1021/cg101597q

Cited by 51 publications

(64 citation statements)

References 26 publications

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“…For crystallisation at neutral pH for aqueous solution; the α polymorph is the expected polymorph. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] The α polymorph has been found in many experiments. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] These experiments were done with a range of volumes, supersaturations etc, thus the preference for the α polymorph (at neutral pH) is a robust result.…”

Section: Polymorphismmentioning

confidence: 96%

“…20 Now, while the γ polymorph can be obtained, [4][5][6][7]11,12,14 the α polymorph is generally found on crystallisation from aqueous solution at neutral pH. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Glycine's solubility is very sensitive to temperature, 21 making it easy experimentally to vary the supersaturation. The α polymorph has a very fast growth rate (radial growth rates on the order of 1 mm/s have been observed 17 ).…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8][9][10][11][12][13][14][15][16][17] Apart from varying pH, 10 γ glycine has been obtained by applying an electric field, 33 adding salts 34,35 or in emulsion systems using the anionic surfactant AOT. 6,7 It is unusual to observe γ glycine without using one of these methods specifically to induce γ nucleation. Our findings may be useful; the pharmaceutical industry often wants the equilibrium polymorph, and we found it without varying the pH, adding salt, etc..…”

Section: Introductionmentioning

confidence: 99%

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Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

Little

Sear

Keddie

2015

Crystal Growth & Design

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We quantitatively study the crystallisation of glycine from solution, by following the crystallisation of a plate with 96 wells, each with 0.1 ml of supersaturated solution. Our first aim is to address the difficult problem of obtaining nucleation data that is reproducible. This problem is difficult due to the extreme sensitivity of nucleation times. Nucleation is sensitive to factors that include how the crystallising system is prepared, and even small (1%) variations in the supersaturation. We discuss the appropriate statistical tests needed to show reproducibility.Our second aim is to study the competition between the nucleation of the alpha and gamma polymorphs of glycine. We find that nucleation appears to be heterogeneous: some samples crystallise in minutes, while others do not crystallise after days, which indicates that there is no well defined nucleation rate for the set of samples. Homogeneous nucleation gives a well-defined rate. Those samples that crystallise in minutes mostly yield the metastable alpha polymorph. We speculate that these crystals may be the result of seed crystals formed by transient local increases in supersaturation in pipette tips during sample preparation. However, those that crystallise in hours are largely in the equilibrium gamma polymorph. This is perhaps surprising as typically the alpha polymorph is obtained from crystallisation from aqueous solutions near neutral pH. We speculate that the nucleation rate of the gamma polymorph may be higher than that of the alpha form, but that in earlier work with larger solution volumes (increasing the probability of seeding) and with stirring, the alpha polymorph dominates because of its much faster growth rate.

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Section: Polymorphismmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

Little

Sear

Keddie

2015

Crystal Growth & Design

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“…From aqueous solution, glycine typically crystallises into the metastable α form, not into the equilibrium γ polymorph. 2 Controlling which polymorph forms is often of crucial importance, especially in the pharmaceutical industry. 3 Failure to control the polymorph that forms can be disastrous, as illustrated by the problems experienced in the late 1990s with the anti-HIV (human immunodeficiency virus) drug ritonavir.…”

Section: Introductionmentioning

confidence: 99%

Nucleation of crystals that are mixed composites of all three polymorphs in the Gaussian core model

Mithen

Callison

Sear

2015

The Journal of Chemical Physics

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Articles you may be interested inCross-nucleation between clathrate hydrate polymorphs: Assessing the role of stability, growth rate, and structure matching J. Chem. Phys. 140, 084506 (2014) We present results of computer simulations of homogeneous crystal nucleation in the Gaussian core model. In our simulations, we study the competition between the body-centered-cubic (bcc), face-centered-cubic (fcc), and hexagonal-close-packed crystal phases. We find that the crystal nuclei that form from the metastable fluid phase are typically "mixed"; they do not consist of a single crystal polymorph. Furthermore, when the fcc phase is stable or fcc and bcc phases are equally stable, this mixed nature is found to persist far beyond the size at the top of the nucleation barrier, that is, far into what would be considered the growth (rather than nucleation) regime. In this region, the polymorph that forms is therefore selected long after nucleation. This has implications. When nucleation is slow, it will be the rate-limiting step for crystallization. Then, the step that determines the time scale for crystallisation is different from the step that controls which polymorph forms. This means that they can be independently controlled. Also between nucleation and polymorph selection, there is a growing phase that is clearly crystalline not fluid, but this phase cannot be assigned to any one polymorph. C 2015 AIP Publishing LLC. [http://dx

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“…The transient dimer mechanism also enables crystallization to proceed in microemulsions whenever a transient dimer forms between a droplet containing a crystal nucleus and a nucleus-free droplet which contains supersaturated solution, since the crystal nucleus can then gain access to this supersaturated solution and thereby grow (see Figure 6). Crystallization of organic compounds from microemulsions was first studied by Füredi-Milhofer et al in 1999 for the aspartame crystal system, with studies on glycine crystallization (Allen et al, 2002;Yano et al, 2000;Chen et al, 2011) and carbamazepine (Kogan et al, 2007) following. The use of microemulsions in producing both inorganic nanoparticles and macroscopic organic crystals shows that the size of the particulates grown can vary from a few nm to mm, depending upon the nucleation rate, the ability to form stable nuclei, and the extent of surfactant adsorption on the resulting particles.…”

Section: Microemulsionsmentioning

confidence: 99%

Crystallization in Microemulsions: A Generic Route to Thermodynamic Control and the Estimation of Critical Nucleus Size

Cooper¹,

Cook²,

Loines³

2012

Crystallization - Science and Technology

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Leapfrogging Ostwald’s Rule of Stages: Crystallization of Stable γ-Glycine Directly from Microemulsions

Cited by 51 publications

References 26 publications

Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

Nucleation of crystals that are mixed composites of all three polymorphs in the Gaussian core model

Crystallization in Microemulsions: A Generic Route to Thermodynamic Control and the Estimation of Critical Nucleus Size

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