During the last twenty years, the interest towards the development of chiral compound has
exponentially been increased. Indeed, the set-up of suitable asymmetric enantioselective synthesis protocols
is currently one of the focuses of many pharmaceutical research projects. In this scenario, chiral
HPLC separations have gained great importance as well, both for analytical- and preparative-scale applications,
the latter devoted to the quantitative isolation of enantiopure compounds. Molecular modelling
and quantum chemistry methods can be fruitfully applied to solve chirality related problems especially
when enantiomerically pure reference standards are missing. In this framework, with the aim to
explain the molecular basis of the enantioselective retention, we performed computational studies to
rationalize the enantiomer elution order with both low- and high-molecular weight chiral selectors.
Semi-empirical and quantum mechanical computational procedures were successfully applied in the
domains of chiral ligand-exchange and chiral ion-exchange chromatography, as well as in studies dealing
with the use of polysaccharide-based enantioresolving materials.