Glycine Polymorphism in Nanoscale Crystallization Chambers

Abstract

Crystallization of glycine by evaporation of aqueous solutions in nanometer-scale channels of controlled-pore glass (CPG) powders and porous polystyrene-poly(dimethyl acrylamide) (p-PS-PDMA) monoliths, the latter prepared by etching polylactide (PLA) from aligned PS-PDMA-PLA triblock copolymers, preferentially results in exclusive formation of the β polymorph, which is not observed during crystallization in bulk form under identical conditions. X-ray diffraction (XRD) reveals that the dimensions of the embedded crystals are commensurate with the pore diameter of the matrix. β-Glycine persists for at least one year in CPG and p-PS-PDMA with pore diameters less than 24 nm, but it transforms slowly to R-glycine over several days when confined within 55 nm CPG. Moreover, variable temperature XRD reveals that β-glycine nanocrystals embedded within CPG are stable at temperatures at which bulk β-glycine ordinarily transforms to the R form. XRD and differential scanning calorimetry (DSC) reveal the melting of glycine nanocrystals within CPG below the temperature at which bulk glycine melts with concomitant decomposition. The melting point depression conforms to the Gibb-Thompson equation, with the melting points decreasing with decreasing pore size. This behavior permits an estimation of the melting temperature of bulk β-glycine, which cannot be measured directly owing to its metastable nature. Collectively, these results demonstrate size-dependent polymorphism for glycine and the ability to examine certain thermal properties under nanoscale confinement that cannot be obtained in bulk form. The observation of β-glycine at nanometer-scale dimensions suggests that glycine crystallization likely involves formation of β nuclei followed by their transformation to the other more stable forms as crystal size increases, in accord with Ostwald's rule of stages.

Effect of Nanoscale Confinement on the Crystallization of Potassium Ferrocyanide

“…However, that significant confinement effects have been observed in every inorganic crystal system that we have examined suggests that this phenomenon has a common underlying physical mechanism. Further, that these effects can operate even on the micron-scale shows that this does not originate from the pore-size dependent stabilization of critical nuclei, as is often suggested for organic compounds 39,40,62 .…”

Controlling Polymorphism in Pharmaceutical Compounds Using Solution Shearing

“…[14][15][16][17] Recently, nanoscale confinement methods such as crystallization in controlled pore glass and nanodrops have shown great utility in obtaining metastable polymorphs of numerous pharmaceutical compounds. [18][19][20][21][22] These results suggest that there is a fundamental connection between confined environments and metastable crystallization. However, these methods do not yield significant amounts of the metastable polymorph for further testing and processing.…”

“…33 Confinement has been shown to be a parameter that influences polymorphism and crystallization, however confinement is a surface dominated phenomenon that cannot be effectively accomplished in a bulk crystallization system. 19 If we wish to utilize the fundamental information that polymorphism arises from confinement, then we must use a surface dominant (as opposed to volumetric) approach to crystallization. Shearing is a confined system, as the thickness of thin films is dimensionally limited by surface tension and the spacing between the shear surface and the blade.…”

Mineralization and non-ideality: on nature’s foundry

“…For example, vesicular structures containing mineral precursors are involved in bone development and sea urchin spiculogenesis (Mahamid et al 2011;Vidavsky et al 2014). Although the effects of macromolecule-or vesicle-based confinement at different length scales on mineralization are not completely clear, some possible explanations for the distinct nucleation behavior are (1) a confinement size-dependent interplay between homogenous and heterogeneous nucleation (Woo et al 2007), (2) critical size constraints corresponding to crystal nuclei (or ion-associates) and related polymorph selectivity (Ha et al 2004), and (3) size constraint-driven thermodynamic crossovers in phase stability (Hamilton et al 2008;Navrotsky 2004;Raiteri and Gale 2010), as well as distinct solvent dynamics and physicochemical conditions in restricted environments and the bulk solvent (Brubach et al 2001;Moilanen et al 2007;. Taken together, biomacromolecular crowding conditions as well as the interfacial aspects and size regime of confinement appear evolutionarily optimized for modulating the nucleation regime including associated phase transition events.…”