A clear and predictive understanding of the propensity for crystallisation of one polymorph over another is lacking, and in this regard glycine is a model system due to difficulties in crystallisation of the thermodynamically stable gamma polymorph. The preferential crystallisation of gamma-glycine in the presence of micellar CTAB (Cetyltrimethylammonium bromide) as opposed to the alpha form commonly crystallised from pure solution was observed. A rationale for this result was sought through the observation of the nucleation and growth kinetics of the alpha and gamma polymorphs of glycine (and DL-alanine) using in situ microscopy, the measurement of induction times and following the solution mediated phase transformation of alpha-glycine. These observations help explain the dominant crystal form produced in a number of solutions.The nucleation and growth rates of alpha-glycine were shown to be orders of magnitude greater than those of gamma-glycine in pure solution. Also, the addition of a cationic surfactant (such as CTAB) or modification of the solution pH were shown to dramatically accelerate the nucleation and growth of polar gamma-glycine and DL-alanine, a rarely reported phenomenon. In addition, the growing (00-1) faces of gamma-glycine and DL-alanine, at which growth was accelerated, were shown to be macroscopically rough, indicating a growth mechanism dominated by nucleation rather than the growth of layers.The most likely cause of the inhibited kinetics of gamma-glycine and DL-alanine is water bound electrostatically at the negatively charged (00-1) faces, while the growth acceleration inferred by the additives is related to their ability to release water from these surfaces. Other mechanisms which may play a role include the adsorption of adventitious impurities, strong electrostatic repulsion between like-charged carboxylate groups at the (00-1) surface resulting in structural disorder, and the effect of surface energy on the rate of surface nucleation.This research provides an important example of nature's complexity in selecting crystal form in polymorphic systems, gives further insight into the causes of the asymmetric growth of polar crystal structures, and introduces the possibility that the crystallisation kinetics of 'difficult' slow growing compounds may sometimes be modified through the use of additives.
|Date of Award||31 Dec 2012|
- The University of Manchester
|Supervisor||Robin Curtis (Supervisor)|