The interaction mechanism of a variety of racemic alkyl aryl sulfoxides with a pi-acid HPLC stationary phase containing N,N'-(3,5-dinitrobenzoyl)-trans-1, 2-diaminocyclohexane chiral selector was investigated by means of quantum-chemical calculations (MNDO), partial least squares (PLS) analysis, and 3D comparative molecular field analysis (CoMFA). Quantitative structure-enantioselective retention relationships (QSERR), were derived which have yielded significant insights into physicochemical properties primarily responsible for chiral recognition. The increase in retention (k') is favored especially by the analyte pi-basic character, accounted for by the sum of the electrophilic superdelocalizabilities of all aromatic carbon atoms (S(Ph)HOMO), and to minor extent by the H-bond basicity of the sulfoxide oxygen and the hydrophilicity of solutes. In contrast, the separation factor (alpha) varied mainly with the steric properties of the substituents and with polar and electrostatic properties of the sulfoxide group. A 3D-QSERR analysis using CoMFA methodology has provided a more complete description of factors responsible for chiral recognition and has proven to be a useful tool to examine differences in noncovalent fields (both the electrostatic and the steric) mostly associated with variations of enantioselectivity. (C) 1993 Wiley-Liss, Inc