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Dynamic Behavior of Clobazam on High‐Performance Liquid Chromatography Chiral Stationary Phases
Author(s) -
Sabia Rocchina,
De Martino Michela,
Cavazzini Alberto,
Villani Claudio
Publication year - 2016
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22542
Subject(s) - chemistry , enantiomer , clobazam , chiral column chromatography , high performance liquid chromatography , chirality (physics) , chromatography , circular dichroism , stereochemistry , computational chemistry , chiral symmetry breaking , symmetry breaking , nambu–jona lasinio model , physics , quantum mechanics , neuroscience , epilepsy , biology
Clobazam, a 1,5‐benzodiazepin‐2,4‐dione, is a chiral molecule because its ground state conformation features a nonplanar seven‐membered ring lacking reflection symmetry elements. The two conformational enantiomers of clobazam interconvert at room temperature by a simple ring‐flipping process. Variable temperature HPLC on the Pirkle type (R)‐N‐(3,5‐dinitronenzoyl)phenylglycine and (R,R)‐Whelk‐O1 chiral stationary phases (CSPs) allowed us to separate for the first time the conformational enantiomers of clobazam and to observe peak coalescence‐decoalescence phenomena due to concomitant separation and interconversion processes occurring on the same time scale. Clobazam showed temperature dependent dynamic high‐performance liquid chromatography (HPLC) profiles with interconversion plateaus on the two CSPs indicative of on‐column enantiomer interconversion. (enantiomerization) in the column temperature range between T col = 10°C and T col = 30°C, whereas on‐column interconversion was absent at temperature close to or lower than T col = 5°C. Computer simulation of exchange‐deformed HPLC profiles using a program based on the stochastic model yielded the apparent rate constants for the on‐column enantiomerization and the corresponding free energy activation barriers. At T col = 20°C the averaged enantiomerization barriers, ΔG ‡ , for clobazam were found in the range 21.08–21.53 kcal mol −1 on the two CSPs. The experimental dynamic chromatograms and the corresponding interconversion barriers reported in this article are consistent with the literature data measured by DNMR at higher temperatures and in different solvents. Chirality 28:17–21, 2016 . © 2015 Wiley Periodicals, Inc.