. (2011) 'Stable polymorphs crystallized directly under thermodynamic control in three-dimensional nanocon nement : a generic methodology.', Crystal growth design., 11 (2). pp. 363-366. Further information on publisher's website:https://doi.org/10.1021/cg101200fPublisher's copyright statement:This document is the Accepted Manuscript version of a Published Work that appeared in nal form in Crystal growth design, copyright c American Chemical Society after peer review and technical editing by the publisher. To access the nal edited and published work see https://doi.org/10.1021/cg101200fAdditional information:Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThermodynamic control of crystallization has been achieved to produce stable polymorphs directly by using 3D nano-confinement in microemulsions. The theoretical basis for thermodynamic control of crystallization using 3D nano-confinement is outlined. Our approach leap-frogs the usual metastable polymorph pathway because crystallization becomes governed by the ability to form stable nuclei, rather than critical nuclei. The generality of this approach is demonstrated by crystallizing the stable polymorph of three 'problem' compounds from microemulsions under conditions yielding metastable forms in bulk solution. The polymorphic compounds are mefenamic acid (2-[(2,3-(dimethylphenyl)amino] benzoic acid), glycine (aminoethanoic acid) and the highly polymorphic 5-methyl-2-[(2-nitrophenyl) amino]-3-thiophenecarbonitrile, commonly known as ROY because of its red, orange and yellow polymorphs. Application of this methodology should prevent another Ritonavir-type disaster, whereby a marketed drug transforms into a more stable form, reducing its bioavailability and effectiveness. The lowest energy nuclei selectively grow in our approach. Consequently this also provides a generic method for producing higher crystallinity materials, which may prove beneficial for crystallizing proteins and inorganic nanocrystals.Statement of urgency and brief summary of significant findings. We believe the paper fulfills the requirements of urgency for a Communication because it details for the first time a generic method to obtain thermodynamic control of crystallization. This enables stable polymorphs to be crystallized directly, to prevent another Ritonavir-type disaster. The methodology used selectively grows the lowest energy crystal nuclei, so it can also produce materials with higher crystallinity, which may prove of use for a wide range of crystalline materials, including potential...

In crystallization, the critical nucleus size is of pivotal importance. Above this size, it is favorable for the new crystalline phase to form; below this size, the clusters will tend to dissolve rather than grow. To date, there has been no direct method for measuring the critical nucleus size. Instead, the size is typically calculated from the variation of crystallization rates with temperature. This involves using bulk values of the interfacial tension and enthalpy of fusion, which are inappropriate for small critical nucleus sizes. Here, we present a direct method for measuring the size of the critical nucleus, based on observing crystallization temperatures of materials within microemulsions. Using this approach, the number of molecules in the critical nucleus can be found simply by measuring the droplet size. Data on the freezing of water in water-in-oil microemulsions with and without the nucleating agent, heptacosanol, are presented to support our hypothesis. The results show that the critical nucleus contains 90-350 ice molecules for water pool radii of approximately 1.2-1.8 nm for the heptacosanol-doped microemulsions in which heterogeneous nucleation is initiated at the droplet interface. For the microemulsions without heptacosanol, the critical nucleus contains 70-210 ice molecules for water pool radii of approximately 1.2-1.8 nm. The smaller values arise because homogeneous nucleation occurs and therefore the crystallization temperatures are lower. We can also determine how bulk properties are perturbed at the nanoscale, and we find that the ratio of the ice-water interfacial tension to the enthalpy of fusion decreases significantly for water pool radii that are <2 nm.

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The present research was designed to test the hypothesis that children would compete more in tetrads than in dyads. Twenty-two pairs of male and 14 pairs of female target children (N = 72) played a competitive game in both tetrads and dyads. Consistent with the hypothesis, male target children competed more in tetrads than in dyads. This hypothesis was not supported for females, however. Analyses of the dynamics of tetrads and dyads further demonstrated that based on a global measure of smiling, the emotional atmosphere was less positive in tetrads than in dyads. The causes and consequences of interaction in different sized social groups are discussed.

Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. For small confinement volumes, phase transition temperatures are determined by the scarcity of the crystallizing material, rather than the magnitude of the energy barrier, as the supply of molecules undergoing the phase transition can be depleted before a stable nucleus is attained. We show this for the case of crystallization from the melt and from the solution by using a simple model based on an extended classical nucleation theory. This has important implications because it enables a simple and direct measurement of the critical nucleus size in crystallization. It also highlights that predicting the observable melting points of nanoparticles by using the Gibbs-Thomson equation can lead to substantial errors.