On the structure of an aqueous propylene glycol solution

Abstract

Using a combination of neutron diffraction and empirical potential structure refinement computational modelling, the interactions in a 30 mol. % aqueous solution of propylene glycol (PG), which govern both the hydration and association of this molecule in solution, have been assessed. From this work it appears that PG is readily hydrated, where the most prevalent hydration interactions were found to be through both the PG hydroxyl groups but also alkyl groups typically considered hydrophobic. Hydration interactions of PG dominate the solution over PG self-self interactions and there is no evidence of more extensive association. This hydration behavior for PG in solutions suggests that the preference of PG to be hydrated rather than to be self-associated may translate into a preference for PG to bind to lipids rather than itself, providing a potential explanation for how PG is able to enhance the apparent solubility of drug molecules in vivo.

On the solvation of the phosphocholine headgroup in an aqueous propylene glycol solution

“…The hydrogenbonding interactions between the PG hydroxyl groups with water molecules and water molecules with themselves suggest that the the hydrogen bonds have similar strength to one another as they all show a sharp first peak peak at 1.86Å. The relative intensity of the peaks observed in these functions can be attributed to local density effects, or excluded volume effects where this has been previously observed for aqueous PG in the absence of C 3 -PC at the same concentration, 16 and for acetone and DMSO in aqueous solutions. 39 The coordination numbers in Table 3 indicate that EPSR fits to the neutron data show slightly increased water-water coordination and slightly reduced PG-water interactions compared to the MD simulation.…”

“…In addition, the PG-water coordination numbers are comparable to the degree of hydrogen bonding in aqueous PG at the same concentration. 16 Overall, there are only minor changes to the structure of this solution, suggesting PC does not perturb the solution, in either simulation. Figure 4 (a) shows the g(r)s for water and PG hydroxyl solvation (from the R-isomer, the S-isomer-PC interations are shown in the SI) around the -N(CH 3 ) + 3 (onium group) on C 3 -PC for both EPSR and MD and Table III shows the coordination numbers for these functions.…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Neutron diffraction experiments have been used to study an aqueous solution of 30 mol% PG, containing 200 mM of 1,2-dipropionyl-sn-glycero-3-phosphocholine (C 3 -PC). The neutron diffraction experiments were performed on the SAN-DALS diffractometer at the ISIS neutron facility, UK.…”

On the structure of prilocaine in aqueous and amphiphilic solutions

“…Empirical potential structure refinement is a Monte Carlo based simulation specifically designed to model the structure of liquids and other disordered materials. 32 EPSR is a technique which has been used in combination with NDIS measurements to determine the local structure of a variety of molecules in solution, 10,15,[20][21][22][23][24][26][27][28]33 and is unique as it uses a set of measured diffraction data as a constraint for resultant computational model. By beginning with a set of starting potentials, Lennard-Jones and appropriate charges in the present work, these potentials are iteratively refined until the molecular structure is consistent with the measured F(Q) data.…”

On the hydration of DOPE in solution

“…As a result, Empirical Potential Structure Refinement (EPSR) simulations were employed, where this Monte Carlo-based simulation technique has been specifically designed to generate a computational model of a disordered system which fits a set of measured diffraction data in order to extract a full set of correlations for any given system. 19,20 This analysis method has been used to explore a range of chemical and biological solutions, [21][22][23][24][25][26][27][28][29][30] as well as specifically for the hydration of lipid molecules. 10,[12][13][14]31 Here EPSR simulations were performed on a box containing 10 DOPE, 50 H 2 O and 3000 CHCl 3 molecules at the temperature and atomic number density of the measurement (298 K and 0.0374 atoms/Å 3 ).…”