Study on the separation of ofloxacin enantiomers by hydroxyl-propyl-β-cyclodextrin as a chiral selector in capillary electrophoresis: a computational approach

Abstract

Hydroxypropyl-b-cyclodextrin (HPbCD) has been used successfully as a chiral additive to separate ofloxacin (OFL) enantiomers in a capillary electrophoresis system. Using electrospray-mass spectrometry (ESI-MS) it was revealed that OFL forms an inclusion complex with HPbCD at 1:1 stoichiometry. The interaction of the enantiomers with the host was further investigated by molecular modeling using molecular mechanics dockings, PM7 semiempirical calculations and molecular dynamics simulations. Calculations using PM7 semiempirical methods indicated that the separation is brought about by a large difference in the binding energies (DDE) of 15 kcal mol -1 between R-OFL-HPbCD and S-OFL-HPbCD inclusion complexes. S-OFL was predicted to be eluted first by the PM7 method which corroborates the experimental results. Moreover, the molecular dynamic simulations show that the formation of stable R-OFL-HPbCD is because it is more deeply inserted into the cavity of the host. The study also revealed the absence of the role of strong hydrogen bonding in the enantioseparations.

Recent studies of docking and molecular dynamics simulation for liquid‐phase enantioseparations

“…Therefore, the question of modelling substituted CDs has been addressed. For example, Suliman and co‐workers built the structure of 2‐hydroxypropyl‐βCD starting from the βCD structure by substitutions of 2‐hydroxypropyl moieties randomly at O2 and O6 positions of the glucosyl monomers as a representation for the 2‐hydroxypropyl‐βCD mixtures. The authors noted that a precise description of the structure of chemically modified CDs is not realistic because of the wide range of random substitution patterns occurring during derivatization.…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…Suliman et al. performed the chiral separation of ofloxacin by using 40 mM HP‐β‐CD as the CS . CE data were then combined with ESI‐MS and molecular modeling studies were performed.…”

“…Therefore, a lot of theoretical and computational approaches on the chiral separation of several analytes were performed, and the separation mechanisms were investigated. Suliman et al performed the chiral separation of ofloxacin by using 40 mM HP-␤-CD as the CS [45]. CE data were then combined with ESI-MS and molecular modeling studies were performed.…”

Application of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE‐C4D): An update

“…The generally short duration of method development, the simple instrumentation and the use of small sample and electrolyte volumes are, of course, interesting from economic and environmental friendliness point of view (Altria, Kelly, & Clark, ; Nishi, ). The main application areas of CE in drug analysis are in chiral separation (Suliman & Elbashir, ; Suliman, Elbashir, & Schmitz, ), active ingredient assay and impurity determination (Al Azzam, Saad, Makahleah, Aboul‐Enein, & Elbashir, ). In this section the applications of CE with C 4 D for pharmaceutical analysis are overviewed.…”