Gamma-valerolactone (GVL) is a cyclic ester that can be considered a green alternative in chemical processes due to its environmentally friendly physical and chemical properties and low production cost from biomass. Although GVL is a chiral solvent, it is usually used as a racemic mixture, instead of its homochiral forms, which might improve its performance in enantioselective synthesis and chiral separation chromatographic techniques. This report presents the development and validation of an atomistic force field optimized to reproduce GVL liquid-phase properties via Monte Carlo (MC) and molecular dynamics (MD) simulation methods. The optimized force field improved the description of the interactions between pairs of molecules, which is a key aspect for a proper assessment of subtle interactions between the enantiomeric forms of GVL. Inspection of radial distribution functions (RDF) for correlations between RR, SS, and RS interactions found within GVL racemic mixture shows very subtle differences at the first solvation shell. Average interaction energies [Formula: see text], [Formula: see text] and [Formula: see text] for RR, SS, and RS dimer ensembles, respectively, were calculated with force field and also HF-3c and PBEh-3c quantum chemistry methods. For each methodology, resulting values obtained for [Formula: see text] and [Formula: see text] were almost the same and more negative than [Formula: see text]. Also, the average energy fluctuation obtained for RR and SS dimers were higher than the one obtained for RS.
Keywords: Chiral solvents; Dimer ensemble; Enantioselective interactions; Gamma-valerolactone; Greener solvents.