Polymorph selectivity under nanoscopic confinement

Polymorph selectivity has been achieved during crystallization of anthranilic acid (AA) and 5-methyl-2-[(2-nitrophyenyl)amino]-3-thiophenecarbonitrile (ROY), both considered benchmarks of polymorphic behavior, within nanoporous glass beads and polymer monoliths. Whereas polymorph III of AA crystallizes from the melt on nonporous glass beads or within larger pores, the metastable polymorph II crystallizes in pores with diameters <23 nm, with the selectivity toward this form increasing with decreasing pore size. Of the six ROY polymorphs characterized by single-crystal X-ray diffraction, the yellow form (Y) crystallizes during evaporation of pyridine solutions imbibed by the 30-nm cylindrical pores of porous polycyclohexylethylene (p-PCHE) monoliths. Although both R and ON grow from the melt on the external surfaces of PCHE, only the red form (R) crystallizes in the pores. Amorphous ROY also forms in p-PCHE pores during evaporation from pyridine solutions, subsequently crystallizing to the R nanocrystals upon heating. Although heterogeneous nucleation on the pore walls may play a role, these observations suggest that nucleation and polymorph selectivity is governed by critical size constraints imposed by the ultrasmall pores. The ability to achieve polymorph selectivity in both glass and polymer matrices suggests wide-ranging compatibility with various organic crystalline solids, promising a new approach to controlling polymorphism and searching for unknown polymorphs.     

Controlled nucleation from solution using polymer microgels

Despite its widespread occurrence in nature and broad application in industrial practice, nucleation of crystalline materials remains largely unpredictable and therefore difficult to control. In this work, we demonstrate a new method to control nucleation with polymer microgels by tuning their microstructure to vary systematically the degree of nanoscopic confinement and its effects on nucleation. We find that the polymer microstructure has a significant impact on nucleation kinetics. Moreover, there exists an optimum polymer mesh size at which the rate of nucleation is dramatically enhanced, the degree to which depends on the extent of polymer-solute interactions. With easily tunable microstructure and chemistry, polymer microgels offer a promising approach for the rational design of materials for controlling nucleation from solution.     

Polymorph selectivity of an AIE luminogen under nano-confinement to visualize polymer microstructures

Despite the huge progress of luminescent molecular assemblies over the past decade, it is still challenging to understand their confined behavior in semi-crystalline polymers for constrained space recognition. Here, we report a polymorphic luminogen with aggregation-induced emission (AIE), capable of selective growth in polymer amorphous and crystalline phases with distinct color. The polymorphic behaviors of the AIE luminogen embedded within the polymer network are dependent on the size of nano-confinement: a thermodynamically stable polymorph of the AIE luminogen with green emission is stabilized in the amorphous phase, while a metastable polymorph with yellow emission is confined in the crystalline phase. The information on polymer crystalline and amorphous phases is transformed into distinct fluorescence colors, allowing a single AIE luminogen as a fluorescent marker for visualization of polymer microstructures in terms of amorphous and crystalline phase distribution, quantitative polymer crystallinity measurement, and spatial morphological arrangement. Our findings demonstrate that confinement of the AIE luminogen in the polymer network can achieve free space recognition and also provide a correlation between microscopic morphologies and macroscopic optical signals. We envision that our strategy will inspire the development of other materials with spatial confinement to incorporate AIE luminogens for various applications.

A polymorphic AIEgen is capable of selective growth in amorphous and crystalline polymer phases with distinct color for microstructure visualization.     

Nucleation of one polymorph by another

Nucleation of one polymorph by another has been observed directly in the melt crystallization of d-mannitol and d-sorbitol. The new polymorph nucleated on an existing one and grew to dominate the end product. This effect is relevant to controlling polymorphism in the manufacture of specialty chemicals and to developing theories of polymorphic nucleation and concomitant polymorphs, for which current efforts emphasize homogeneous nucleation of alternative polymorphs.     

Cross-nucleation between ROY polymorphs

Cross-nucleation between polymorphs is a newly discovered phenomenon important for understanding and controlling crystal polymorphism. It contradicts Ostwald's law of stages and other theories of crystallization in polymorphic systems. We studied the phenomenon in the spontaneous and seeded melt crystallization of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY), currently the most polymorphic system of known structures. We observed extensive and sometimes selective cross-nucleation between ROY polymorphs. Certain polymorphs could not nucleate without the aid of others. The new polymorph was found to be more or less thermodynamically stable than the initial one but to always grow faster than or as fast as the initial one. The temperature and surface characteristics of the seed crystals affected the occurrence of cross-nucleation. Our results show that the pathway of crystallization in polymorphic systems is not determined solely by the initial nucleation, but also by cross-nucleation between polymorphs and the different growth rates of polymorphs. This study identified a new metastable polymorph of ROY, the 10th of the family.     

Alteration of polymorphic selectivity through different crystallization mechanisms occurring in the same crystallization solution

We report a case in which two different crystallization mechanisms occurring in the same crystallization experiment are found to yield different polymorphic outcomes. In particular, we focus on crystallization of glycine from neutral aqueous solution. Crystallization in the bulk solution gives only the metastable alpha-polymorph, as observed in previous studies, whereas crystallization by evaporation of a thin film of the solution on the walls of the crystallization vessel is found to give rise to the thermodynamically stable gamma-polymorph, and furthermore produces an uncharacteristic crystal morphology for this polymorph. A detailed set of control experiments are described that elucidate mechanistic details relating to the latter crystallization process. The fact that crystallization on the walls of a crystallization vessel can yield a different polymorphic outcome from crystallization in the bulk solution in the same experiment has potentially much wider significance with regard to other polymorphic systems.     

Utilization of Evaporation during the Crystallization Process: Self‐Templation of Organic Parallelogrammatic Pipes

Analogues of 4‐dodecyloxy‐2‐trifluoromethylbenzamide ( 12FH2 ) consisting of a hydrophobic alkyl chain, a trifluoromethylated aromatic ring, and a self‐complementary hydrogen‐bonding amido group were synthesized, and the structural effect of each component on the formation of parallelogrammatic pipes was investigated. Differential scanning calorimetry and powder XRD analyses revealed that all‐trans L and gauche‐rich S polymorphic forms appeared for the analogues with more than eight carbon atoms in the alkyl chain, that is, the polymorphism originates in the conformation of the alkyl groups and hydrogen‐bonding patterns of the benzamide group. Also, the trifluoromethyl substituent is crucial in that it provides an appropriate molecular balance between the benzamide and alkyl groups. Scanning electron microscopy and powder XRD analyses of solids obtained by a drying‐mediated assembly process revealed that production of the L polymorph by polymorphic transition from the S polymorph resulted in evolution of a three‐dimensional structure when the alkyl group has more than 12 carbon atoms. Among the series of compounds, 12FH2 and 4‐tetradecyloxy‐2‐trifluoromethylbenzamide ( 14FH2 ) formed parallelogrammatic pipes with micrometer dimensions. An atomic force microscopy study of 12FH2 suggested that a single pipe may be composed of platelike crystallites of L polymorph. From a mercury‐intrusion porosimetry study, it was determined that macroporous materials with average pore diameters of about 40 μm and porosity of about 80 % were obtained. The previously proposed self‐templation mechanism by polymorphic transition from S to L polymorph was further discussed in view of polymorphism and the crystallization rate. An appropriate molecular balance between the benzamide and alkyl groups is necessary to induce a proper polymorphic transition for the development of a three‐dimensional hollow structure in the evaporation process.     

Polymer microgels: reactors for semiconductor, metal, and magnetic nanoparticles

We report a strategy for the production of materials with structural hierarchy. The approach employs polymer microgels as templates for the synthesis of semiconductor, metal, or magnetic nanoparticles (NPs). We show that NPs with predetermined dimensions and size-dependent properties can be synthesized by using a very delicate balance between the reaction conditions, the composition and the structure of microgel templates, and the concentration of NPs in the microgel. Postheat treatment of microgels doped with semiconductor nanoparticles reduces NP polydispersity and allows control of their photoluminescence. Microgel templates are particularly beneficial in the synthesis of polymer microspheres heavily loaded with monodisperse superparamagnetic Fe(3)O(4) NPs. Hybrid submicrometer-size microgels have promising potential applications in photonics, catalysis, and separation technologies.     

Molecular mechanism for the cross-nucleation between polymorphs

We use molecular simulations to study the early stages of crystallization in a supercooled liquid of Lennard-Jones particles. We observe the onset of concomitant polymorphism and demonstrate that this phenomenon results from the cross-nucleation of a metastable polymorph on the stable polymorph. We also show that cross-nucleation is selective as it only takes place between polymorphs of almost equivalent free energy. Our simulations provide detailed insights into the molecular mechanism underlying concomitant polymorphism and cross-nucleation between polymorphs.     

Luminescence Color‐Tuning through Polymorph Doping: Preparation of a White‐Emitting Solid from a Single Gold(I)–Isocyanide Complex by Simple Precipitation

We report the luminescent color tuning of a new complex, 2‐benzothiophenyl(4‐methoxyphenyl isocyanide)gold(I) ( 1 ), by using a new “polymorph doping” approach. The slow crystallization of the complex 1 afforded three different pure polymorphic crystals with blue, green, and orange emission under UV‐light irradiation. The crystal structures of pure polymorphs of 1 were investigated in detail by means of single‐crystal X‐ray analyses. Theoretical calculations based on the single‐crystal structures provided qualitative explanation of the difference in the excited energy‐levels of the three polymorphs of 1 . In sharp contrast, the rapid precipitation of 1 , with the optimized conditions reproducibly afforded homogeneous powder materials showing solid‐state white‐emission with Commission Internationale de l’Éclairage (CIE) 1931 chromaticity coordinates of (0.33, 0.35), which is similar to pure white. New “polymorphic doping” has been revealed to be critical to this white emission through spectroscopic and X‐ray diffraction analyses. The coexistence of the multiple polymorphs of 1 within the homogeneous powder materials and the ideal mixing of multiple luminescent colors gave its white emission accompanied with energy transfer from the predominant green‐emitting polymorph to the minor orange‐emitting polymorph.     

聚合物在受限层空间中的形态结构演变及相关性能研究进展

自然界中的层状有序结构如强韧的贝壳、树木等,往往带来优异的性能或特殊的功能。作为仿生材料学在高分子加工成型技术中的应用,聚合物微纳层共挤出技术是通过特殊的流道设计对聚合物熔体进行多次强制分割叠加,来制备高性能交替多层聚合物材料的新方法。层倍增器单元对熔体的多重力场作用,为多相多组分体系形态的原位调控提供了可能。而通过两相交替层状排布形成的受限层空间和丰富的层界面不仅赋予了材料独特的力学、光电、阻隔等性能,还为聚合物结晶调控提供了理想的研究模型。本文简要综述了近年来在层倍增过程中聚合物的形态结构演变及其对相关性能影响方面的研究进展。     

Crystallization of a salt of a weak organic acid and base: solubility relations, supersaturation control and polymorphic behavior

Control of crystallization processes for organic salts is of importance to the pharmaceutical industry as many active pharmaceutical materials are marketed as salts. In this study, a method for estimating the solubility product of a salt of a weak acid and weak base from measured pH-solubility data is described for the first time. This allows calculation of the supersaturation of solutions at known pH. Ethylenediammonium 3,5-dinitrobenzoate is a polymorphic organic salt. A detailed study of the effects of pH, supersaturation, and temperature of crystallization on the physical properties of this salt shows that the desired polymorph may be produced by appropriate selection of the pH and supersaturation of crystallization. Crystal morphology is also controlled by these crystallization conditions.     

The phase (trans)formation and physical state of a model drug in mesoscopic confinement

Compounds embedded into mesoporous or even microporous matrices are interesting for many emerging applications, such as novel catalysts, sensors, batteries, hydrogen storage materials or modern drug delivery devices. We report on two unexpected phenomena regarding the structural and dynamic properties of a model drug substance (indomethacin) when confined in mesoscopic matrices. Firstly, we show that the confinement directs the crystallization of the drug into a stable polymorph that is not otherwise formed at all; its relative amount depends on the pore size. This phenomenon is also explained theoretically using a modified classical heterogeneous nucleation theory. Secondly, we demonstrate that--even at relatively low volume fractions--the confined drug forms a condensed phase in a way that obstructs the passage of the pore channels. This may have far-reaching consequences for understanding the mechanisms of drug release from porous matrices.     

Confined crystallization of polymers within anodic aluminum oxide templates

In this article, a review of recent literature on confined crystallization within nanoporous anodic aluminum oxide (AAO) templates is presented. For almost all infiltrated polymeric materials, crystal orientation within the nanopores is a function of pore diameter. T_c and T_m usually decrease and are a function of pore size. When no pore interconnection remains, the crystallization occur at large supercoolings in heterogeneity free environments. Hence, the nucleation mechanism changes from heterogeneous to surface or homogeneous nucleation. The crystallization kinetics of infiltrated polymers should be close to first order, since in confined environments nucleation is the determining step of the overall crystallization and Avrami indexes (n) of ～1 (or lower in some cases) should be obtained. Examples are provided where these conditions have been met and first order kinetics (n = 1) were measured as opposed to higher orders (n = 3?4) for the same polymer in the bulk. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1179–1194     

On the mechanism of crystalline polymorph selection by polymer heteronuclei

The phase-selective crystallization of acetaminophen (ACM) using insoluble polymers as heteronuclei was investigated in a combined experimental and computational effort to elucidate the mechanism of polymer-induced heteronucleation (PIHn). ACM heteronucleates from supersaturated aqueous solution in its most thermodynamically stable monoclinic form on poly(n-butyl methacrylate), whereas the metastable orthorhombic form is observed on poly(methyl methacrylate). When ACM crystals were grown through vapor deposition, only the monoclinic polymorph was observed on each polymer. Each crystallization condition leads to a unique powder X-ray diffraction pattern with the major preferred orientation corresponding to the crystallographic faces in which these crystal phases nucleate from surfaces of the polymers. The molecular recognition events leading to these outcomes are elucidated with the aid of computed polymer-crystal binding energies using docking simulations. This investigation illuminates the mechanism by which phase selection occurs during the crystallization of ACM using polymers as heteronuclei, paving the way for the improvement of methods for polymorph selection and discovery based on heterogeneous nucleation promoters.     

Crystal polymorphism in antioxidant-metal deactivator 1,2-bis(3,5-di-tert-butyl-4-hydroxyhydrocinnamoyl)hydrazine

The important polymer stabilizer, 1,2-bis(3,5-di-tert-butyl-4-hydroxyhydrocinnamoyl)hydrazine, which serves a dual role as a metal deactivator and antioxidant, is shown to have crystal polymorphism. Although the published melting range is 225-232 °C, which is well above the processing temperature of many polymers in which it is used, existence of a second polymorph that transforms below 205 °C is demonstrated. This α polymorph, which is thermodynamically stable at room temperature, is thermodynamically un-favored at temperatures above about 176 °C. It is shown that under some conditions the α polymorph can endothermically pass directly into the melt state at temperatures below 205 °C, while under other conditions it undergoes a direct endothermic solid-solid transition to the higher melting β polymorph.The results highlight the potential importance of polymorphs for controlling polymer additive behavior and elucidate important phenomena relevant to dispersion of this additive in polymer compounds.     

Nanofibrillar Stimulus‐Responsive Cholesteric Microgels with Catalytic Properties

We report composite stimulus‐responsive cholesteric catalytically active microgels derived from filamentous supramolecular building blocks: cellulose nanocrystals (CNCs). The variation in the microgel dimensions and pitch in response to the change in ambient conditions was governed by the polymer component. The cholesteric morphology of the microgels resulted from the self‐organization of CNCs in spherical confinement. The microgels exhibited excellent structural integrity and functioned as microreactors in catalytic hydrolysis reactions and in the synthesis of metal nanoparticles. Because of these collective properties, the reported microgels show much promise for application in the design of functional responsive materials.     

Defects distribution of metallocene and MgCl2-supported Ziegler-Natta isotactic poly(propylenes) as revealed by fractionation and crystallization behaviors

The inter and intramolecular distribution of defects of poly(propylenes) of the Ziegler-Natta (ZN) and metallocene (M) types, with matched molar masses and overall defect concentrations, are inferred from the crystallization and polymorphic behavior of their narrow molecular mass fractions. The fractions obtained from the M-iPP display a range in molecular masses but the same concentration of defects and provide direct evidence of the uniform intermolecular defect distribution and the “single site” nature of the catalyst. The stereodefects of the ZN-iPP fractions are more concentrated in the low molecular mass fractions, corroborating a broad interchain distribution of the nonisotactic content. In addition, the invariance of the linear growth rates among the ZN fractions and very low contents of the gamma polymorph, developed even by the most defected ZN fraction, are consistent with a stereo blocky intramolecular distribution of defects in the ZN-iPP molecules. In contrast to the linear growth rates, which are sensitive to the defect microstructure, the overall crystallization rates correlate with nucleation density and not necessarily with the iPP chain microstructure.     

Preparation of CuS-P(NIPAM-co-MAA)Hybrid Microgels with Controlled Surface Structures

Copper sulfide‐poly(isopropylacrylamide‐co‐methacrylic acid) [CuS‐P(NIPAM‐co‐MAA)] hybrid microgels with patterned surface structures have been synthesized by means of the polymer microgel template technique. The results showed that the surface morphology of the hybrid microgels could be regulated by controlling the decomposition of thioacetamide (TAA) in an acidic medium. The rate of precipitation and the amount of metal sulfide significantly affect the surface structures of the hybrid microgels.     

Selective nucleation and discovery of organic polymorphs through epitaxy with single crystal substrates.

Crystallization of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (1), previously found to produce six conformational polymorphs from solution, on single-crystal pimelic acid (PA) substrates results in selective and oriented growth of the metastable "YN" (yellow needle) polymorph on the (101)(PA) faces of the substrate. Though the freshly cleaved substrate crystals expose (101)(PA) and (111)(PA) faces, which are both decorated with [101](PA) ledges that could serve as nucleation sites, crystal growth of YN occurs on only (101)(PA). Goniometry measurements performed with an atomic force microscope reveal that the (001)(YN) plane contacts (101)(PA) with a crystal orientation [100](YN)//[010](PA) and [010](YN)//[101](PA). A geometric lattice analysis using a newly developed program dubbed GRACE (geometric real-space analysis of crystal epitaxy) indicates that this interfacial configuration arises from optimal two-dimensional epitaxy and that among the six polymorphs of 1, only the YN polymorph, in the observed orientation, achieves reasonable epitaxial match to (101)(PA). The geometric analysis also reveals that none of the polymorphs, including YN, can achieve comparable epitaxial match with (111)(PA), consistent with the absence of nucleation on this crystal face. In contrast, sublimation of 1 on cleaved succinic acid (SA) substrates, which expose large (010)(SA) faces decorated with steps along [101](SA), affords growth of several polymorphs, each with multiple orientations, as well as oriented crystals of a new metastable polymorph on the (010)(SA) surfaces. The lack of polymorphic selectivity on (010)(SA) can be explained by the geometric lattice analysis, which reveals low-grade epitaxial matches between (010)(SA) and several polymorphs of 1 but no inherent selectivity toward a single polymorph. These observations demonstrate the sensitivity of crystal nucleation to substrate surface structure, the potential of crystalline substrates for selective nucleation and discovery of polymorphs, and the utility of geometric lattice modeling for screening of substrate libraries for controlling polymorphism.