(198s) Nanoclustering of Salicylic Acid in Organic Solvents | AIChE

(198s) Nanoclustering of Salicylic Acid in Organic Solvents


Kakkar, S. - Presenter, Synthesis & Solid State Pharmaceutical Centre, University of Limerick
Rasmuson, A., KTH Royal Institute of Technology
Krishnaraj, R. D., Science & Engineering Faculty
In crystallization, the primary step is nucleation, which is a first-order phase transition where solid particles are formed from their components. Nucleation in past was explained with the help of classical nucleation theory (CNT). Nano-clustering explained through two-step nucleation theory (TNT), challenges classical nucleation theory (CNT) as it had shortcomings. The difference in the two theories are in terms of structural and density fluctuations. In CNT, they occur simultaneously however in TNT density fluctuations follow structural fluctuations.[1] Thus, the nanoclusters are highly dynamic in nature, which rearrange themselves with time. In recent times, researchers have found evidences that the theory exist in various proteins[2] and inorganic particles[3], by means of experiments and molecular simulations. In addition, the role of solvent is an important aspect for solute-solute interactions.

My research focuses on the study of nanoclusters formed in salicylic acid as a function of time in different organic solvents. Salicylic acid, an anti-fungal and anti-inflammatory drug, is used in cosmetic industry. With the use of dynamic light scattering, nanoclusters of salicylic acid were studied in ethyl acetate, acetonitrile, methanol and acetic acid solutions at different concentrations at an isothermal condition for a period of 72h. The solutions are undersaturated, saturated and supersaturated at 25°C. With the change in concentration in different solvents, a trend in order of clustering for different solvents was observed, which holds good for the prediction of nucleation order obtained earlier[4]. At all times, the increase in size is observed which states the order of clustering in different solvents. However, these trends tend to change over the period of time. The one with lower cluster size in undersaturated solutions obtains higher cluster size when the solutions are supersaturared however vice versa is also found to be true. In all solvents, a similar size is obtained at saturated concentration.


[1] D. Gebauer, M. Kellermeier, J. D. Gale, L. Bergström, and H. Cölfen, “Pre-nucleation clusters as solute precursors in crystallisation.,” Chem. Soc. Rev., vol. 43, no. 7, pp. 2348–71, 2014.

[2] P. G. Vekilov, “Nucleation of crystals in solution,” AIP Conf. Proc., vol. 1270, pp. 60–77, 2010.

[3] D. Gebauer, A. Völkel, and H. Cölfen, “Stable prenucleation calcium carbonate clusters.,” Science, vol. 322, no. 5909, pp. 1819–22, 2008.

[4] D. Mealey, D. M. Croker, and A. C. Rasmuson, “Crystal nucleation of salicylic acid in organic solvents,” CrystEngComm, vol. 17, no. 21, pp. 3961–3973, 2015.