Combination of capillary electrophoresis, molecular modelling and nuclear magnetic resonance to study the interaction mechanisms between single-isomer anionic cyclodextrin derivatives and basic drug enantiomers in a methanolic background electrolyte.
ABSTRACT In order to improve our knowledge of the mechanisms of enantiomer recognition pattern in nonaqueous systems, an approach combining nonaqueous CE (NACE), molecular modelling and NMR was undertaken. Bupivacaine and propranolol were selected as model compounds and their interactions with two single-isomer highly charged β-CD derivatives, namely heptakis(2,3-di-O-methyl-6-O-sulfo)-β-CD (HDMS-β-CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-β-CD (HDAS-β-CD), were studied. The CD-bupivacaine complexes were evaluated by 2-D Rotating-frame Overhauser Effect SpectroscopY (ROESY) experiments. From these experiments, it can be assumed that inclusion complexes are not formed, whatever the CD derivative used. Molecular modelling was performed at the RHF/MINI-1 or B3LYP/6-31G(d) level. External as well as inclusion type complexes with the alkyl chain of propranolol into both CD cavities were located. Interaction energies calculated for bupivacaine and propranolol correlated with the enantiomer migration order observed in the NACE experiments using both anionic CD derivatives. The interaction of propranolol with HDMS-β-CD or HDAS-β-CD gives rise to a family of external and inclusion complexes in which some are more probably obtained.
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ABSTRACT: Eight single-isomer ammonium-β-cyclodextrin derivatives with different side chains were successfully developed as chiral selectors for the chiral separation of selected racemates in capillary electrophoresis. The number of substituted groups at N-atom as well as the alkyl chain length greatly influenced the chiral separation. With the numbers of hydroxylalkyl groups at N-atom growing, the aqueous solubility of resolving agents were distinctly decreased and chiral separation ability was also significantly reduced. The apparent complex stability constants between CDs and analytes were further determined. The best enantioseparations of hydroxyl acids was achieved with the use of mono-6A-(3-hydroxypropyl)-1-ammonium-β-cyclodextrin chloride and mono-6A-(3-methoxypropyl)-1-ammonium-β-cyclodextrin chloride. The nuclear magnetic resonance experiments were carried out using them with mandelic acid as guest molecules, revealing the inclusion pattern as well as electrostatic interactions and hydrogen bonding interactions as additional chiral driving force. The contribution of potential interaction sites in the sidearm could enhance the enantioseparations.This article is protected by copyright. All rights reservedElectrophoresis 07/2014; · 3.16 Impact Factor
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ABSTRACT: Chiral separation of twelve new triadimenol antifungal active compounds by electrokinetic chromatography and chiral recognition mechanisms by computer-aided molecular modeling techniques were studied. Seven neutral cyclodextrins were used as chiral selectors. Heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) exhibited a very high enantioselectivity power to twelve active compounds compared to the other tested CDs. The influences of the concentration of TM-β-CD, buffer pH, buffer concentration, applied voltage, and temperature were investigated, respectively. Under the optimum separation conditions, all the twelve active compounds were baseline separated and the resolutions of most compounds were beyond 2.50. The study of the analyte structure-enantioseparation relationships showed that substitutions in the side chains played important roles on enantiomeric separation. By means of computer-aided molecular modeling software Discovery Studio 2.5/Sybyl 7.0/Gold 3.0.1, inclusion process between TM-β-CD and these enantiomers was investigated and their binding energies were calculated. The results suggested that the enantioseparation result related to the difference in binding energy. And the good separation obtained in the presence of the TM-β-CD chiral selector was due to the big binding energy difference of two enantiomers with the chiral selector. This article is protected by copyright. All rights reserved.Electrophoresis 02/2014; · 3.16 Impact Factor
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ABSTRACT: Capillary electrophoresis represents a very powerful separation tool in the area of chiral separations. Cyclodextrin mediated chiral CE is a continuously flourishing technique within the frame of the electromigration methods. In this review a brief overview of the synthetic procedures leading to modified cyclodextrins is provided first. Next, selected aspects related to the utilization of cyclodextrins in chiral CE are discussed specifically in the view of recently published data. Advantages of cyclodextrins and basic principles of chiral CE are remained. The topic of the determination of binding constants is touched. Particular attention is paid to the effort aiming at better understanding of the molecular level of the enantiorecognition between cyclodextrins and the analyte in the solution. Powerful approaches extensively utilized in this field are NMR, molecular modelling, and computer simulations. Then a summary of applications of cyclodextrins in the CE enantioseparations is given, covering years 2008-2013. Finally, the general trend of modified cyclodextrins use in separation science is statistically evaluated. This article is protected by copyright. All rights reserved.Electrophoresis 05/2014; 35(19). · 3.16 Impact Factor