Aqueous solutions of well soluble molecules such as small amino acids are usually assumed to be essentially homogenous systems with some degree of local structuring due to specific interactions on the sub-nanometre scale (e.g. molecular clusters, hydration shells) usually not exceeding several solute molecules. However, recent theoretical and experimental studies have indicated presence of mesoscale structures in solutions of small organic and inorganic molecules as well as proteins¹.

We investigated both supersaturated and undersaturated aqueous solutions of two simple amino acids (glycine and DL-alanine) using Small Angle X-ray Scattering (SAXS), Dynamic Light Scattering (DLS) and Brownian Microscopy/Nanoparticles Tracking Analysis (NTA). Colloidal scale mesostructures were previously reported in supersaturated solutions of those amino acids and were implicated as intermediates species on non-classical crystallization pathways^2,3. Surprisingly, we found that these mesostructures were also present in undersaturated solutions at solute concentrations well below the solid-liquid equilibrium (saturation) concentration at a given temperature, with mean sizes ranging from 100 to 300 nm and size distributions widening towards larger sizes with increasing solute concentrations. While DL-alanine mesostructures appeared to be solid-like and could be filtered out by 100 nm syringe PTFE filters, glycine mesostructures were comfortably passing through these filters and are thought to be liquid-like.

Using experimentally measured size distributions of these mesostructures from NTA, SAXS intensity data were fitted using various structural models and an excellent agreement was obtained using a mass fractal model with the fractal dimension d_f=2.7 suggesting fairly compact clusters with highly irregular interfaces. This is not surprising, since it is expected that the surface tension between the mesostructures and surrounding bulk solution would be very low as they only differ in glycine concentration. The result may be an undulating interfacial topology similar to that found in complex surfactant or block-copolymer systems.

We note that these mesostructures are not a separate phase but a part of the liquid solution phase and are in equilibrium with the surrounding bulk solution. Therefore they are also in equilibrium with the solid phase when the overall solution concentration is equal to the saturation concentration at a given temperature. The local concentration of glycine in mesostructures is higher than that in the surrounding bulk solution so when the system is supersaturated nucleation is more likely to occur in them. However, if the nuclei produced are smaller than the critical nucleus size, they will redissolve when they are exposed to the surrounding bulk solution.

1  Vekilov, P. G. Dense Liquid Precursor for the Nucleation of Ordered Solid Phases from Solution. Crystal Growth & Design 4, 671-685, (2004).

2  Ma, Y., Cölfen, H. & Antonietti, M. Morphosynthesis of Alanine Mesocrystals by pH Control. The Journal of Physical Chemistry B 110, 10822-10828, (2006).

3  Jawor-Baczynska, A., Sefcik, J. & Moore, B. D. 250 nm Glycine-Rich Nanodroplets Are Formed on Dissolution of Glycine Crystals But Are Too Small To Provide Productive Nucleation Sites. Crystal Growth & Design, (2012).

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