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Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases
Authors:Michael Lämmerhofer
Institution:Christian Doppler Laboratory for Molecular Recognition Materials, Department of Analytical Chemistry and Food Chemistry, University of Vienna, Waehringer Strasse 38, A-1090 Vienna, Austria
Abstract:An overview of the state-of-the-art in LC enantiomer separation is presented. This tutorial review is mainly focused on mechanisms of chiral recognition and enantiomer distinction of popular chiral selectors and corresponding chiral stationary phases including discussions of thermodynamics, additivity principle of binding increments, site-selective thermodynamics, extrathermodynamic approaches, methods employed for the investigation of dominating intermolecular interactions and complex structures such as spectroscopic methods (IR, NMR), X-ray diffraction and computational methods. Modern chiral stationary phases are discussed with particular focus on those that are commercially available and broadly used. It is attempted to provide the reader with vivid images of molecular recognition mechanisms of selected chiral selector–selectand pairs on basis of solid-state X-ray crystal structures and simulated computer models, respectively. Such snapshot images illustrated in this communication unfortunately cannot account for the molecular dynamics of the real world, but are supposed to be helpful for the understanding. The exploding number of papers about applications of various chiral stationary phases in numerous fields of enantiomer separations is not covered systematically.
Keywords:Ac-Phe  N-acetyl-phenylalanine  AGP  α1-acid glycoprotein  ADMPC  amylose tris(3  5-dimethylphenylcarbamate)  ANN  artificial neural networks  ANOVA  analysis of variance  ATR  attenuated total reflectance  AX  anion-exchanger  CBH  cellobiohydrolase  CE  crown-ether (in context of chiral selector)  CD  circular dichroism (in context of spectroscopy)  CD  cyclodextrin (in context of chiral selector)  CDMPC  cellulose tris(3  5-dimethylphenylcarbamate)  CIS  complexation-induced chemical shift (Δδ)  CLEC  chiral ligand exchange chromatography  CMPA  chiral mobile phase additive  CoMFA  comparative molecular field analysis  CoMSIA  comparative molecular similarity index analysis  CS  chiral selector  CSP  chiral stationary phase  DEA  diethylamine  DNB  3  5-dinitrobenzoyl  DNP  2  4-dinitrophenyl  EEC  enthalpy&ndash  entropy compensation  ELSD  evaporative light scattering detection  FMOC  fluorenylmethoxycarbonyl  Glob-MolInE  global molecular interaction evaluation  HOMO  highest occupied molecular orbital  HILIC  hydrophilic interaction chromatography  HR/MAS  high-resolution magic angle spinning  HSA  human serum albumin  IRE  internal reflection element  Leu  leucine  LFER  linear free energy relationship  LSER  linear solvation energy relationship  LUMO  lowest unoccupied molecular orbital  MCTA  microcrystalline cellulose triacetate  MD  molecular dynamic  MLR  multiple linear regression  MM  molecular mechanics  N-Me-Leu  N-methyl leucine  NOE  nuclear Overhauser effect  NOESY  nuclear Overhauser effect spectroscopy  NP  normal-phase  OVM  ovomucoid  PLS  partial least squares in latent variables  PO  polar organic (mode)  QD  quinidine  QM  quantum mechanical  QN  quinine  QSERR  quantitative structure&ndash  enantioselective retention relationship  QSPR  quantitative structure&ndash  property relationship  QSRR  quantitative structure&ndash  retention relationship  ROE  rotating frame nuclear Overhauser effect  ROESY  rotating frame nuclear Overhauser effect spectroscopy  SA  selectand  SCX  strong cation exchanger  SFC  super-/subcritical fluid chromatography  SMB  simulated moving bed  TAG  teicoplanin aglycone  TFA  trifluoroacetic acid  trNOE  transferred nuclear Overhauser effect  VCD  vibrational circular dichroism  WAX  weak anion-exchanger (WAX)  Wf  warfarin  XRD  X-ray diffraction  ZWIX  zwitterionic ion-exchanger
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