The phase behaviors of crystalline solids embedded within nanoporous matrices have been studied for decades. Classic nucleation theory conjectures that phase stability is determined by the balance between an unfavorable surface free energy and a stabilizing volume free energy. The size constraint imposed by nanometer-scale pores during crystallization results in large ratios of surface area to volume, which are reflected in crystal properties. For example, melting points and enthalpies of fusion of nanoscale crystals can differ drastically from their bulk scale counterparts. Moreover, confinement within nanoscale pores can dramatically influence crystallization pathways and crystal polymorphism, particularly when the pore dimensions are comparable to the critical size of an emerging nucleus. At this tipping point, the surface and volume free energies are in delicate balance and polymorph stability rankings may differ from bulk. Recent investigations have demonstrated that confined crystallization can be used to screen for and control polymorphism. In the food, pharmaceutical, explosive, and dye technological sectors, this understanding and control over polymorphism is critical both for function and for regulatory compliance. This Account reviews recent studies of the polymorphic and thermotropic properties of crystalline materials embedded in the nanometer-scale pores of porous glass powders and porous block-polymer-derived plastic monoliths. The embedded nanocrystals exhibit an array of phase behaviors, including the selective formation of metastable amorphous and crystalline phases, thermodynamic stabilization of normally metastable phases, size-dependent polymorphism, formation of new polymorphs, and shifts of thermotropic relationships between polymorphs. Size confinement also permits the measurement of thermotropic properties that cannot be measured in bulk materials using conventional methods. Well-aligned cylindrical pores of the polymer monoliths also allow determination and manipulation of nanocrystal orientation. In these systems, the constraints imposed by the pore walls result in a competition between crystal nuclei that favors those with the fastest growth direction aligned with the pore axis. Collectively, the examples described in this Account provide substantial insight into crystallization at a size scale that is difficult to realize by other means. Moreover, the behaviors resulting from nanoscopic confinement are remarkably consistent for a wide range of compounds, suggesting a reliable approach to studying the phase behaviors of compounds at the nanoscale. Newly emerging classes of porous materials promise expanded explorations of crystal growth under confinement and new routes to controlling crystallization outcomes.

A method to calculate the location of all Bragg diffraction peaks from nanostructured thin films for arbitrary angles of incidence from just above the critical angle to transmission perpendicular to the film is reported. At grazing angles, the positions are calculated using the distorted wave Born approximation (DWBA), whereas for larger angles where the diffracted beams are transmitted though the substrate, the Born approximation (BA) is used. This method has been incorporated into simulation code (called NANOCELL) and may be used to overlay simulated spot patterns directly onto two-dimensional (2D) grazing angle of incidence small-angle X-ray scattering (GISAXS) patterns and 2D SAXS patterns. The GISAXS simulations are limited to the case where the angle of incidence is greater than the critical angle (alpha(i) > alpha(c)) and the diffraction occurs above the critical angle (alpha(f) > alpha(c)). For cases of surfactant self-assembled films, the limitations are not restrictive because, typically, the critical angle is around 0.2 degrees but the largest d spacings occur around 0.8 degrees 2theta. For these materials, one finds that the DWBA predicts that the spot positions from the transmitted main beam deviate only slightly from the BA and only for diffraction peaks close the critical angle. Additional diffraction peaks from the reflected main beam are observed in GISAXS geometry but are much less intense. Using these simulations, 2D spot patterns may be used to identify space group, identify the orientation, and quantitatively fit the lattice constants for SAXS data from any angle of incidence. Characteristic patterns for 2D GISAXS and 2D low-angle transmission SAXS patterns are generated for the most common thin film structures, and as a result, GISAXS and SAXS patterns that were previously difficult to interpret are now relatively straightforward. The simulation code (NANOCELL) is written in Mathematica and is available from the author upon request.

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.

Controlling polymorphism, the ability of a compound to adopt more than one solid-state structure, often relies on empirical manipulations of conditions such as solvent, temperature, and mode of crystallization. Despite a growing interest in nanocrystalline formulations, however, the influence of crystal size on polymorph formation and stability is largely unexplored. Nanocrystals of pimelic acid, HO 2 C(CH 2 ) n-2 CO 2 H (n = 7), glutaric acid (n = 5), suberic acid (n = 8), and coumarin (1,2-benzopyrone) in nanometer-scale pores of controlled pore glass (CPG) beads and hexagonally ordered cylindrical pores of poly(cyclohexylethylene) (p-PCHE) monoliths exhibit size-dependent polymorphism and thermotropic behavior because of the physical constraints imposed by the dimensions of the pores. Pimelic acid, suberic acid, and coumarin also exhibit heretofore unknown polymorphs, denoted δ-pimelic acid, β-suberic acid, and β-coumarin, in CPG with pore sizes <23 nm and p-PCHE with pore diameters <40 nm. The melting points of the confined crystals decrease monotonically with decreasing pore size, and the enantiotropic phase behavior of bulk glutaric acid and suberic acid switches to monotropic when confined within the nanoscale pores of CPG and p-PCHE. Collectively, these results reveal that nanometer-scale size confinement can alter crystallization outcomes and affect polymorph stability compared with bulk crystallization. Moreover, crystallization in very small pores can lead to the discovery of new polymorphs that otherwise would not be detected using conventional screening methods.