Enantioseparation of novel anti-inflammatory chiral sulfoxides with two cellulose dichlorophenylcarbamate-based chiral stationary phases and polar-organic mobile phase(s)

Abstract

Chiral sulfoxides represent a class of substances of great importance in many fields, including medicinal chemistry dealing with the synthesis of novel cyclooxygenase-2 (COX-2) inhibiting/NO donors. In the present study, two nitrooxyethyl sulfoxides along with their metabolites, hydroxyethyl derivatives have been successfully enantioresolved with two cellulose tris(3,5-dichlorophenylcarbamate)-based chiral stationary phases (CSPs), one with a coated (CSP 1) and the other (CSP 2) with an immobilized chiral selector. The immobilized selector in CSP 2 produced comparable-to-better performances than the coated one in CSP 1 (with α and RS values up to 1.94 and 6.32, respectively) running the analysis with a polar-organic phase made up with an ethanol/2-propanol (80:20, v/v) mobile phase. Electronic circular dichroism studies coupled to ab initio time-dependent density functional theory simulations allowed us to determine the elution order of three out of four compounds. For the two hydroxyethyl derivatives the same enantiomeric elution order [(S)<(R)] was obtained with both CSPs, while the compounds containing the −ONO2 group experienced a different elution order depending on the coated or immobilized nature of the chiral selector [(S)<(R) with CSP 1 and (R)<(S) with CSP 2]. A molecular modeling study based on docking simulations was performed to gain a deeper insight into the enantioseparation mechanism of the hydroxyethyl derivatives on both CSPs.

Keywords

• Coated chiral selector
• Cyclooxygenase-2 inhibitors
• Immobilized chiral selector
• Electronic circular dichroism
• Enantiorecognition mechanism
• In-silico simulations