Micro-Solvation of Propofol in Propylene Glycol-Water Binary Mixtures: Molecular Dynamics Simulation Studies

The water microstructure around propofol plays a crucial role in controlling their solubility in the binary mixture. The unusual nature of such a water microstructure can influence both translational and reorientational dynamics, as well as the water hydrogen bond network near propofol. We have carried out all-atom molecular dynamics simulations of five different compositions of the propylene glycol (PG)/water binary mixture containing propofol (PFL) molecules to investigate the differential behavior of water microsolvation shells around propofol, which is likely to control the propofol solubility. It is evident from the simulation snapshots for various compositions that the PG at high molecular ratio favors the water cluster and extended chainlike network that percolates within the PG matrix, where the propofol is in the dispersed state. We estimated that the radial distribution function indicates higher ordered water microstructure around propofol for high PG content, as compared to the lower PG content in the PG/water mixture. So, the hydrophilic PG regulates the stability of the water micronetwork around propofol and its solubility in the binary mixture. We observed that the translational and rotational mobility of water belonging to the propofol microsolvation shell is hindered for high PG content and relaxed toward the low PG molecular ratio in the PG/water mixture. It has been noticed that the structural relaxation of the hydrogen bond formed between the propofol and the water molecules present in the propofol microsolvation shell for all five compositions is found to be slower for high PG content and becomes faster on the way to low PG content in the mixture. Simultaneously, we calculated the intermittent residence time correlation function of the water molecules belonging to the microsolvation shell around the propofol for five different compositions and found a faster short time decay followed up with long time components. Again, the origin of such long time decay is primarily from the structural relaxation of the microsolvation shell around the propofol, where the high PG content shows the slower structural relaxation that turns faster as the PG content approaches to the other end of the compositions. So, our studies showed that the slower structural relaxation of the microsolvation shell around propofol for a high PG molecular ratio in the PG/water mixture correlate well with the extensive ordering of the water microstructure and restricted water mobility and facilitates the dissolution process of propofol in the binary mixture.