Impact of Molecular Speciation on Crystal Nucleation in Polymorphic Systems:  The Conundrum of γ Glycine and Molecular ‘Self Poisoning'

Abstract

The polymorphism of the simple amino acid glycine has been known for almost a century. It is also known that in aqueous solutions, at the isoelectric point (pI 5.9), the metastable alpha polymorph crystallizes, while the stable gamma form of glycine only nucleates at high and low pH. Despite the importance of understanding the process by which crystals nucleate, the solution and solid-state chemistry underlying this simple observation have never been explored. In this contribution, we have combined solution chemistry, crystallization, and crystallographic data to investigate the mechanisms by which this effect occurs. It is concluded that solution speciation and the consequent interactions between charged species and developing crystal nuclei determine the structural outcome of the crystallization process.

Does the γ Polymorph of Glycine Nucleate Faster? A Quantitative Study of Nucleation from Aqueous Solution

“…For crystallisation at neutral pH for aqueous solution; the α polymorph is the expected polymorph. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] The α polymorph has been found in many experiments. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] These experiments were done with a range of volumes, supersaturations etc, thus the preference for the α polymorph (at neutral pH) is a robust result.…”

“…20 Now, while the γ polymorph can be obtained, [4][5][6][7]11,12,14 the α polymorph is generally found on crystallisation from aqueous solution at neutral pH. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Glycine's solubility is very sensitive to temperature, 21 making it easy experimentally to vary the supersaturation. The α polymorph has a very fast growth rate (radial growth rates on the order of 1 mm/s have been observed 17 ).…”

“…Most previous work reports that for crystallisation from aqueous solution near neutral pH, it is the metastable α polymorph that dominates. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Apart from varying pH, 10 γ glycine has been obtained by applying an electric field, 33 adding salts 34,35 or in emulsion systems using the anionic surfactant AOT. 6,7 It is unusual to observe γ glycine without using one of these methods specifically to induce γ nucleation.…”

Studies of Gamma-Glycine Crystals Grown In the Aqueous Solution of Cesium Chloride

“…The growth of -form of glycine crystals can be done from aqueous solution or gel in the presence of additives, from supersaturated solution irradiated with plane-polarized laser light, or from surfactant based microemulsion and lamellar phases [4][5]. The polymorphism of glycine was explained that the crystallization of the least stable -form and the stable -form from aqu eous solution correlated with conditions that had inhibitory effects on the dimer formation [6][7][8][9]. In this work, -glycine crystals were grown by solution method using cesium chloride as an additive.…”

Growth, X-Rd and Thermal Studies of Ferroelectric Glycine Potassium Sulphate (Gps) Crystals.

“…In particular, the inorganic derivatives of protein amino acids are often attributed to symmetric groups [7] without an inversion centre mostly to polar symmetry groups. Their crystals have properties whose symmetry is described by odd -rank tensors such as pyro-electric effect, spontaneous electric polarization, piezoelectric effect, generation of second optical harmonics, [8,9] etc. Single crystals of Tri-Glycine Potassium Sulphate crystals (TGPS), a semi organic nonlinear optical material has been grown from solution by slow evaporation at ambient temperature [10,11] .…”