Abstract

Molecular dynamics (MD) simulations were used to investigate the intermolecular interactions between 1,1’-bi-2-naphthol (BOH) and lorazepam enantiomers and the chiral molecular micelle, poly-(sodium undecyl-(L,L)-leucine-valine). The molecular micelle investigated is of interest because it is used to separate drug enantiomers.  These separations are important because the enantiomers or mirror image forms of some drugs have different physiological properties. The molecular micelle is a polymer composed of twenty covalently bonded monomer chains. The overall goal of the project was to characterize the fundamental intermolecular interactions between the drug enantiomers and the molecular micelle.  Analyses of the free energies of binding, solvent accessible surface areas, hydrogen bonding interactions, water shells, and ligand orientation were used to rationalize the enantiomers’ behavior when bound to the molecular micelle. BOH enantiomers preferentially bound in binding sites where they had favorable orientations with respect to the molecular micelle surface and hydrocarbon core. Similarly, the lorazepam enantiomers oriented in such a way that favorable hydrophobic interactions occurred between their aromatic rings and the molecular micelle core.