Crystallization under nanoscale confinement

Abstract

Classical crystal growth models posit that crystallization outcomes are determined by nuclei that resemble mature crystal phases, but at a critical size where the volume free energy of nuclei begins to offset the unfavorable surface free energy arising from the interface with the growth medium. Crystallization under nanoscale confinement offers an opportunity to examine nucleation and phase transformations at length scales corresponding to the critical size, at which kinetics and thermodynamics of nucleation and growth intersect and dramatic departures in stability compared to bulk crystals can appear. This tutorial review focuses on recent investigations of the crystallization of organic compounds in nanoporous matrices that effectively provide millions of nanoscale reactors in a single sample, ranging from controlled porous glass (CPG) beads to nanoporous block-copolymer monoliths to anodic aluminum oxide (AAO) membranes. Confinement of crystal growth in this manner provides a snapshot of the earliest stages of crystal growth, with insights into nucleation, size-dependent polymorphism, and thermotropic behavior of nanoscale crystals. Moreover, these matrices can be used to screen for crystal polymorphs and assess their stability as nanocrystals. The well-aligned cylindrical nanoscale pores of polymer monoliths or AAO also allow determination of preferred orientation of embedded nanocrystals, affording insight into the competitive nature of nucleation, critical sizes, and phase transition mechanisms. Collectively, these investigations have increased our understanding of crystallization at length scales that are deterministic while suggesting strategies for controlling crystallization outcomes.

Molecular Dynamics Simulations of Hydroxyapatite Nanopores in Contact with Electrolyte Solutions: The Effect of Nanoconfinement and Solvated Ions on the Surface Reactivity and the Structural, Dynamical, and Vibrational Properties of Water

“…Specifically, it is well-recognized that many features of crystal growth are affected by confinement [1][2][3][4][5][6][7] and solution composition [2,[8][9][10][11][12]. Confinement can enable control over size, polymorphism and orientation, single crystal/polycrystalline structure, and morphology [13].…”

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.…”

Effect of Nanoscale Confinement on the Crystallization of Potassium Ferrocyanide

“…As an alternative to additive-directed crystallization, it is also becoming increasingly evident that the micro-environments in which crystals form can themselves define crystallization pathways and products. [15][16][17][18][19] Not only is this of particular importance to processes that naturally occur in confinement such as weathering, biomineralization and the manufacture of nanomaterials, but confinement can potentially provide a stand-alone means of controlling crystallization.…”

“…A number of studies have focused on organic compounds, where these have shown effects such as the stabilization of amorphous and metastable phases, and preferred orientation. 18,20,21 Looking then at biologically-relevant solids such as calcium carbonate and calcium sulfate, confined volumes can provide environments that can control the formation of single crystals with complex morphologies. 7,[22][23][24] Using systems including a crossedcylinders apparatus, 19,25,26 arrays of picolitre droplets, 27 vesicles that offer confinement in the general range 50 nm -50 m, [28][29][30] and the pores of track-etched membranes, [31][32][33] it has also been demonstrated that the lifetimes of amorphous precursor phases and metastable crystalline polymorphs of calcium carbonate, calcium phosphate, calcium sulfate and calcium oxalate can be significantly extended, even in micron-scale environments.…”