Study of enantioseparation mechanisms using capillary electrophoresis and NMR techniques

Author: Ann Gogolashvili
Co-authors: Bezhan Chankvetadze, Lali Chankvetadze, Elene Tatunashvili, Antonio Salgado
Keywords: Capillary Electrophoresis, Chiral separation, NMR Spectroscopy
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The major goal of this project is to explore a potential of CE as a powerful tool for investigation of fine mechanisms of enantioselective intermolecular interactions. This is done basically by using cyclodextrins and their derivatives as one of the counterparts (a selector) and various group of chiral compounds (mostly, but not limited to, chiral drugs), as other counterpart (a selectand) of these interactions. Cyclodextrins, as chiral selectors, have following advantages: a) These are macrocyclic oligosaccharides with a medium size (molecular weight ranges from 900 to 3000 for different native and derivatized cyclodextrins) and well characterized structure; b) Cyclodextrins are transparent in UV-range that makes application of CE with UV-VIS detector easy (Most common CE instruments are equpped with UV-VIS detector). c) Most of native and single component cyclodextrin derivatives have well defined H-NMR and 13-C-NMR spectra that makes application of various nuclear Overhauser effect (NOE) based methods feasible for elucidation of structure of cyclodextrin complexes with chiral analytes. After 30 years since its introduction chiral CE is well established technology for analytical separation of enantiomers. To the major advantages of CE belong high plate numbers, operation in a single phase and advantages associated to this, easy adjustment of enantiomer migration order (EMO), possibility of generation of high separation selectivity from rather low thermodynamic selectivity of recognition, fast screening of chiral selectors, short method development time, easy combination of chiral selectors, etc. Until now still less recognized, and as the consequence less employed, remains high potential of this technique for sensing very weak effects in intermolecular interactions. High sensitivity of CE for detection of weak intermolecular recognition relies on high separation efficiency (theoretical plate numbers) of this technique. Thus, for instance, the thermodynamic selectivity of recognition 1.01 is sufficient for observing baseline resolved peaks in CE while this is not the case in chromatographic techniques even with the most advanced packing materials, column technologies and instrumentation. In addition to this, no immobilization of receptor/selector is required in CE and real physiological conditions can be mimicked easier compared to chromatographic techniques. The most innovative approach in the present project is to view CE as a powerfull technique for studying (enantioselective) noncovalent intermolecular interactions. Quite innovative is the project methodology considering combination of CE, NMR spectroscopy MM in order to reach the above mentioned goal. Another methodological novelty is an experimental validation of molecular modeling techniques for computing the structure of and the forces in cyclodextrin complexes with various analytes. This means in particular following: In MM there are various force fields available for minimizing energy and deriving possible structure of intermolecular complexes. Few variations of density functional approach are also available for the same purpose. These calculation methods can be applied for computing the structures and computed structures compared with experimentally derived ones based on NOE-based experiments in NMR spectroscopy.