Enantioresolution in electrokinetic chromatography-complete filling technique using sulfated gamma-cyclodextrin. Software-free topological anticipation

Few papers have tried to predict the resolution ability of chiral selectors in capillary electrophoresis for the separation of the enantiomers of chiral compounds. In a previous work, we have used molecular information available on-line to establish enantioresolution levels of basic compounds using highly sulfated β-CD (HS-β-CD) as chiral selector in electrokinetic chromatography-complete filling technique (EKC-CFT). The present study is a continuation of this previous work, introducing some novelties. In this work, the ability of sulfated γ-cyclodextrin (S-γ-CD) as chiral selector in EKC-CFT is modelled for the first time. Thirty-three structurally unrelated cationic and neutral compounds (drugs and pesticides) are studied. Categorical enantioresolution levels (RsC, 0 or 1) are assigned from experimental enantioresolution values obtained at different S-γ-CD concentrations. Novel topological parameters connected to the chiral carbon (C*-parameters) are introduced. Four C*-parameters and a topological parameter of the whole molecule (aromatic atom count) are the most important variables according to a discriminant partial least squares-variable selection process. It suggests the preponderance of the topology adjacent to the chiral carbon to anticipate the RsC levels. A software-free anticipation protocol for new molecules is proposed. Over the current set of molecules evaluated, 100% of correct anticipations (resolved and non-resolved compounds) are obtained, while anticipation of some compounds remains undetermined. A criterion is introduced to alert on compounds which should not be anticipated.