title: 3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: A fascinating molecular framework to study the enantioseparation ability of the amylose (3,5-dimethylphenylcarbamate) chiral stationary phase. Part I. Structure-enantioselectivity relationships.
abstract: Chiral stationary phases (CSPs) based on amylose (3,5-dimethylphenylcarbamate) (ADMPC) exhibit a wide-range of enantioselectivity in high-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC). Although this class of CSPs has been extensively used, chiral discriminations at receptorial level, which are useful to develop predictive molecular models, have been rarely reported in the literature. Herein, we describe the results obtained in the enantioselective HPLC of a set of six C5-chiral 4,5-dihydro-(1H)-pyrazole derivatives on the ADMPC-based Chiralpak AD-3 CSP (CSP) under normal-phase and polar organic conditions. Using pure methanol as a mobile phase the exceptional enantioseparation factor value of 50 at 25°C was found for one of the investigated analytes. To the best of our knowledge, the enantiomeric bias represents the most outstanding enantioseparation ever recorded on ADMPC-based CSPs. Systematic variations in chemical groups in specific positions of the 3-(phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole molecular framework resulted in peculiar changes in retention and enantioselectivity. A careful analysis of the chromatographic data permitted to advance some hypotheses concerning the role played by the individual chemical groups in determining the exceptional enantioseparation. In particular, under methanol-rich mode, the prenyl moiety of the second eluted enantiomer of the better resolved analyte was recognized as a critical structural element to establish direct and favorable solvophobic interactions with apolar portions of selector.
authors.affiliation: Dipartimento di Farmacia, Università "G. D'Annunzio" di Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pierini
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Menta
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Fioravanti
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: rcirilli@iss.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cirilli
mesh_terms: D000688:Amylose / Q000031:analogs & derivatives / Q000737:chemistry*; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D025924:Chromatography, Supercritical Fluid; D048448:Phenylcarbamates / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C504080:3,5-dimethylphenylcarbamate; D048448:Phenylcarbamates; D011720:Pyrazoles; C080033:Chiralpak AD; D000688:Amylose
keywords: Chiral stationary phase; Chiralpak AD-3; Enantiomer separation; Receptorial-like enantioselectivity; Solvophobic interaction; Structure-enantioselectivity relationships