| Abstract [eng] |
Hydrotropes are defined as compounds capable of increasing the aqueous solubility of poorly soluble organic compounds. Thus hydrotropes can be applied to increase the solubility of poorly soluble drugs -- which is a common problem in the pharmaceutical industry. Although hydrotropy has been a known phenomena for over a century the underlying mechanism is still being debated. Literature shows that the hydrotropic ionic liquid, choline salicylate, can increase the aqueous solubility of drug molecules up to 6,000-fold. In this work, theoretical methods -- specifically molecular dynamics (MD) simulations -- are used to model the changes in the first solvation shell of the drug molecule ibuprofen within mixtures of hydrotropic salts and water, aiming to explain the molecular mechanism of hydrotropy. Furthermore, a hybrid quantum mechanics/molecular dynamics (QM/MD) method is used to model the 1H NMR spectrum of ibuprofen and the structural changes reflected within it. Analysis of the trajectories obtained via MD simulations reveals that a higher hydrotropic effect within the cholinium salicylate systems is driven by the close coordination of the choline cation around the benzene ring of ibuprofen -- as the introduction of choline ions into the solution results in the most effective displacement of water molecules as compared with the other modelled systems. Although the salicylate anion and ibuprofen molecule both share the structural motif of an aromatic benzene ring, the typical pi-pi stacking interaction has been shown to not occur. The calculated 1H NMR spectrum of ibuprofen in aqueous solution is in agreement with the corresponding experimental spectrum. However, the calculated spectra for the hydrotrope mixtures do not reflect the structural changes that were observed in the MD trajectory analysis. |
