Resolving the longstanding riddle of pH-dependent outcome of glycine polymorphic nucleation

Han, Guangjun; Thirunahari, Satyanarayana; Chow, Pui Shan; Tan, Reginald B. H.

doi:10.1039/c2ce26594j

Cited by 40 publications

(78 citation statements)

References 43 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: 99%

“…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%

“…It is an ideal model system that has been studied extensively in earlier work. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Glycine is an easy-to-work-with molecule, which forms three polymorphs: α, γ and β . The γ polymorph is the most stable of the glycine polymorphs.…”

Section: Introductionmentioning

confidence: 99%

“…Most previous work reports that for crystallisation from aqueous solution near neutral pH, it is the metastable α polymorph that dominates. [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.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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 choose glycine because it is a well studied model system for studies of nucleation of crystals from solution 2,3,6,10,12,13,[16][17][18][19][20][21][22][23][24][25][26][27][28] . Glycine has three polymorphs: α, γ and β. α glycine is the most common polymorph to crystallise from aqueous solution at neutral pH, but the γ polymorph is the most stable of the glycine polymorphs 29 .…”

Section: A Previous Work On Glycinementioning

confidence: 99%

Controlling the crystal polymorph by exploiting the time dependence of nucleation rates

Little

King

Sear

et al. 2017

The Journal of Chemical Physics

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Most substances can crystallise into two or more different crystal lattices, called polymorphs. Despite this, there are no systems in which we can quantitatively predict the probability of one competing polymorph forming, instead of the other. We address this problem using large scale (hundreds of events) studies of the competing nucleation of the alpha and gamma polymorphs of glycine. In situ Raman spectroscopy is used to identify the polymorph of each crystal. We find that the nucleation kinetics of the two polymorphs is very different. Nucleation of the alpha polymorph starts off slowly but accelerates, while nucleation of the gamma polymorph starts off fast but then slows. We exploit this difference to increase the purity with which we obtain the gamma polymorph by a factor of ten. The statistics of the nucleation of crystals is analogous to that of human mortality, and using a result from medical statistics we show that conventional nucleation data can say nothing about what, if any, are the correlations between competing nucleation processes. Thus we can show that, with data of our form, it is impossible to disentangle the competing nucleation processes. We also find that the growth rate and the shape of a crystal depends on when it nucleated. This is new evidence that nucleation and growth are linked.

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Impact of malonic acid on the segregation of glycine polymorphs – Analytical assisted molecular approach

Devi

Srinivasan

2015

Crystal Research and Technology

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Proton dissociation assisted negative polarity of malonic acid molecules admist glycine zwitterions leads to orgination of γ nucleation in the solution. Alteration in the nucleation behaviour and segregation of glycine polymorphs in the presence of malonic acid over a wide range of concentrations has been investigated both by experimental and analytical approaches. Complete changeover in the nucleation behaviour from 100% α to 100% γ is observed at the critical concentration of the additive. Shifting in the overall charge environment of the system towards cationic in the presence of malonic acid favours the nucleation of γ through induced charge compensation in the solution. Tuning of merohedral twinning in γ nucleation by the additive concentration has been well revealed in the present work. CNT based analytical approach employed elucidates well the experimental observations through the estimated interfacial energy, volume excess free energy, critical radius, activation energy barrier and nucleation rates of α and γ polymorphs. Structural affirmation of the nucleated polymorphs was carried out by powder x-ray diffraction.

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Resolving the longstanding riddle of pH-dependent outcome of glycine polymorphic nucleation

Cited by 40 publications

References 43 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

Controlling the crystal polymorph by exploiting the time dependence of nucleation rates

Impact of malonic acid on the segregation of glycine polymorphs – Analytical assisted molecular approach

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