Low Temperature Dynamic Chromatography for the Separation of the Interconverting Conformational Enantiomers of the Benzodiazepines Clonazolam, Flubromazolam, Diclazepam and Flurazepam

Benzodiazepines (BZDs) are an important class of psychoactive drugs with hypnotic-sedative, myorelaxant, anxiolytic and anticonvulsant properties due to interaction the GABAa receptor in central nervous system mammals. BZDs interesting both clinical forensic toxicology for their pharmacological characteristics potential abuse. The presence a non-planar diazepine ring generates chiral conformational stereoisomers, even absence stereogenic centers. A enrichment BZD at binding sites has been reported literature, thus making stereodynamic screening wide range BZDs. Herein, we report investigation three stereolabile 1,4-benzodiazepine included “designer benzodiazepines” (e.g., diclazepam, chloro-derivative diazepam, two triazolo-benzodiazepines, flubromazolam clonazolam) commercially available known as flurazepam, order study kinetic “ring-flip” process that allows enantiomers interconvert high rate room temperature. combination low temperature enantioselective dynamic chromatography on stationary phase computer simulations experimental chromatograms allowed us measure activation energies enantiomerization (ΔG‡) lower than 18.5 kcal/mol. differences between compounds have correlated pattern substitutions 1,4-benzodiazepinic core.