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
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DOI：
10.1021/acs.cgd.5b00938
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发表时间：
2015-11-01
影响因子：
3.8
通讯作者：
Keddie, Joseph L.
中科院分区：
文献类型：
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作者：
Little, Laurie J.;Sear, Richard P.;Keddie, Joseph L.
我们定量地研究了甘氨酸从溶液中结晶的过程，通过跟踪96孔板的结晶，每孔有0.1 mL的过饱和溶液。我们的第一个目标是解决获得可重复成核数据的难题。这个问题很困难，因为成核时间非常敏感。成核对各种因素都很敏感，包括结晶系统的制备方式，甚至过饱和的微小变化（1%）。我们讨论了显示再现性所需的适当统计检验。我们的第二个目的是研究甘氨酸α多晶和γ多晶成核之间的竞争。我们发现成核似乎是不均匀的：一些样品在几分钟内结晶，而另一些样品在几天后不结晶，这表明对这组样品没有明确的成核速率。均相成核给出了一个明确的速率。那些在几分钟内结晶的样品大多产生亚稳态α多晶。我们推测这些晶体可能是样品制备过程中移液管尖端局部过饱和瞬间增加而形成的种子晶体的结果。然而，那些在几个小时内结晶的主要是平衡γ多晶。这可能是令人惊讶的，因为典型的α多晶是在接近中性ph的水溶液中结晶得到的。我们推测，α多晶的成核速率可能高于α形式，但在早期的研究中，在较大的溶液体积（增加播种的可能性）和搅拌下，α多晶占主导地位，因为它的生长速度要快得多。
We quantitatively study the crystallization of glycine from solution by following the crystallization 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 because of the extreme sensitivity of nucleation times. Nucleation is sensitive to factors that include how the crystallizing 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 crystallize in minutes, whereas others do not crystallize 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 crystallize 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 crystallize in hours are largely the equilibrium gamma polymorph. This is perhaps surprising because typically the alpha polymorph is obtained from crystallization 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.