(83a) The Unexpected Nucleation/Polymorphic Transformation-Promoting Effect of Glycine on Crystallisation of L-Glutamic Acid

There has been a widely accepted view that molecular modifiers in solution are capable of directing growth morphology, but have only neutral or inhibitory effects on primary nucleation and growth kinetics. While the former belief still remains unchallenged, the latter one was recently questioned by in-situ atomic force microscopy (AFM) studies on biomineralisation of calcite, which have shown that two acidic proteins dramatically accelerate calcite growth while still altering the surface morphology through interactions with specific atomic steps on the (104) face^1,2. In spite of scarcity of data that exists, one may ask a more general question, ‘Should accelerating effects occur for the primary nucleation of polymorphic materials in the presence of selectively chosen molecular modifiers, and how these initial conditions may, at the later stage, influence the kinetics of solution mediated transformation of metastable to stable polymorphic form’?

Remarkably, for the first time, we found in our research on the influence of various amino acids on crystallisation of dimorphic L-glutamic acid (LGA) that glycine used as a doping material significantly enhances both nucleation and solution-mediated polymorphic transformation rates with respect to the pure system.

The effect of the additive level was investigated using laser-light scattering and concentration evolution monitoring techniques. It was observed that the LGA nucleation/polymorphic transition rates increase with increasing concentration of the doping agent. Furthermore, investigation of the initial product crystal samples using scanning electron microscopy (SEM) indicated that glycine promotes primary nucleation of the β form of L-glutamic acid. Several mechanisms to explain why this previously unreported effect may occur were suggested.

We believe that our findings would be interesting and stimulating for both industrial and scientific communities. The insights derived from these studies could facilitate the design of potent new synthetic nucleation/transformation modulators for diverse polymorphic systems. Ultimately, this would allow better control of the transformation process between polymorphs of crystalline materials in a wide range of consumer products, from foods, through cosmetics to pharmaceuticals.

References:
1. Elhadj, S., De Yoreo, J.J., Hoyer, J.R. and Dove, P.M., Proc. Natl. Acad. Sci. USA, 2006, 103, 19237.
2. Fu, G., Qiu, S.R., Orme, C.A., Morse, D.E. and De Yoreo, J.J., Adv. Mater., 2005, 17, 2678.