Probing Crystal Nucleation from Fluid Phases: The Nucleation of para-Azoxyanisole from Its Nematic Liquid Crystalline State

Abstract

Detailed understanding of structural evolution during the process of crystal nucleation is limited. In this contribution nucleation from the single component nematic phase of para-azoxyanisole is studied with particular emphasis on the structural relationships between liquid crystalline and crystalline phases in this polymorphic system. The data are interpreted and discussed in terms of their relevance to processes occurring within a nucleating cluster. It is clear that while positional order in the supersaturated phase does dictate the structural outcome of crystallization, an activation barrier still exists limiting the overall kinetics of the nucleation process.

Nucleation of Organic Crystals—A Molecular Perspective

“…For example, a study of the crystallization of p-azoxyanisole from its melt by the use of a combination of SAXS/ WAXS, FTIR spectroscopy, and X-ray crystallography illustrated that the first phase to form from a hexagonally packed nematic liquid is not the stable crystal form but a metastable crystalline polymorph with a packing [59] related to the orientational order of the nematic phase. If this macroscopic behavior is taken as a model for nucleation in a supersaturated solution, then it becomes apparent that the nucleation pathway involves clusters in which molecules first adopt the weakly ordered nematic packing before undergoing a phase transition to a fully ordered crystal form.…”

Time-Resolved X-ray Phase-Contrast Imaging (XPCI) of Nucleation and Crystal Growth in the Anti-Solvent Crystallization of Lovastatin

“…The continuous-flow lovastatin crystallization thus shows evidence for heterogeneous nucleation of two forms, first the 2D phase formed form adhering oil droplets on the walls of the outer Kapton tubing and second the nucleation of needle-like crystals at the interface between the 2D phase and the supersaturated solution. The time-lapse lapse images of the formation of a pseudo hexagonal thin-film phase (Figure 5) are reminiscent of similar Stranski-Krastanov growth phenomena, for example as observed in ice 56 and p-azoxyanisole 57 . An animated GIF image of this film growth can be found in the supporting information.…”

“…Lovastatin is widely known to exhibit a needle-like habit 49 that causes problems with processing and manufacturing of API [49][50][51][52][53][54][55][56][57][58] during filtering 58 and due to poor flow properties. 59 This morphology is known to arise from solvent interactions leading to slow growth of various facets.…”

Professor Roger Davey: Master ofAllCrystal Trades

“…However, the topic clearly intrigued him as for example evidenced in his commentary of a 2004 Nature paper, and “...in the end, I succumbed.” Shortly thereafter, he indeed started publishing on nucleation where he tried linking solution chemistry (investigated via infrared spectroscopy) to growth units and to crystal nucleation. , For this, he focused on a series of carboxylic acids and found that this first approach worked just well enough to get hooked on the topic. With Janbon et al and Burton et al he extended this approach to new techniques and substancesin turn gaining an ever deeper understanding of the interplay of solution structure and nucleation. And then, with Sullivan et al, he (finally) started measuring kinetics and hunted for transition states appearing in nucleation. , Were they experimentally measurable?…”