Nuclear magnetic resonance enantiomers

Dale, J. A. and Mosher, H. S., 1973. Nuclear magnetic resonance enantiomer reagents. Configurational correlations via nuclear magnetic... 

Dale, J.A., and H.S. Mosher Nuclear Magnetic Resonance Enantiomer Reagents. Configurational Correlations via Nuclear Magnetic Resonance Chemical Shifts of Diastereomeric Mandelate, 0-Methylmandelate, and a-Methoxy-a-trifluoromethyl-phenylacetate (MTPA) Esters. J, Amer. Chem. Soc., 95, 512 (1973). 

Figure 1 Configurational correlation model for (/ )-MTPA and (S)-MTPA derivatives of secondary carbinols and amines. Reprinted with permission from Dale JA and Mosher HS (1973) Nuclear magnetic resonance enantiomer reagents. Configuration correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, 0-methylmandelate, and a-methyl-a-trifluoromethylphenylacetate (MTPA) esters. Journal of the American Chemical Society 95 512-519. Copyright (1973) American Chemical Society.

The absolute configuration of the 9,10-dihydrodiol metabolite was established to be 9R,10R both by nuclear magnetic resonance spectroscopy and by the structures of the hydrolysis products formed from the svn and anti 9,10-dihydrodio 1-7,8-epoxides which were synthesized from the same 9,10-dihydrodiol enantiomer (13). The absolute configuration of a BaP trans-9.10-dihvdrodiol enantiomer, after conversion to a tetrahydro product, can also be determined by the exciton chirality method (Figure 2) (19.20). 

Enantiomers have identical chemical and physical properties in the absence of an external chiral influence. This means that 2 and 3 have the same melting point, solubility, chromatographic retention time, infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) spectra. However, there is one property in which chiral compounds differ from achiral compounds and in which enantiomers differ from each other. This property is the direction in which they rotate plane-polarized light, and this is called optical activity or optical rotation. Optical rotation can be interpreted as the outcome of interaction between an enantiomeric compound and polarized light. Thus, enantiomer 3, which rotates plane-polarized light in a clockwise direction, is described as (+)-lactic acid, while enantiomer 2, which has an equal and opposite rotation under the same conditions, is described as (—)-lactic acid. 

Nuclear Magnetic Resonance Spectroscopy Measured in a Chiral Solvent or with a Chiral Solvating Agent. One method of NMR analysis for enantiomer composition is to record the spectra in a chiral environment, such as a chiral solvent or a chiral solvating agent. This method is based on the diastereomeric interaction between the substrate and the chiral environment applied in the analysis. 

More recently, enantiomer ratios have been used as evidence of adulteration in natural foods and essential oils. If the enantiomer distribution of achiral component of a natural food does not agree with that of a questionable sample, then adulteration can be suspected. Chiral GC analysis alone may not provide adequate evidence of adulteration, so it is often used in conjunction with other instrumental methods to completely authenticate the source of a natural food. These methods include isotope ratio mass spectrometry (IRMS), which determines an overall 13C/12C ratio (Mosandl, 1995), and site-specific natural isotope fractionation measured by nuclear magnetic resonance spectroscopy (SNIF-NMR), which determines a 2H/ H ratio at different sites in a molecule (Martin et al 1993), which have largely replaced more traditional analytical methods using GC, GC-MS, and HPLC. 

T. Williams et al., Diastereomeric solute-solute interactions of enantiomers in achiral solvents. Nonequivalence of the nuclear magnetic resonance spectra of racemic and optically active dihydroquinine. J. Am. Chem. Soc. 91, 1871-1872 (1969)... 

Saturation transfer difference nuclear magnetic resonance experiments have shown that there is a strong interaction between the enzyme and the (R)-enantiomers of the alcohols, but not the (S)-enantiomers (H. W. Anthonsen, unpublished results). As described above, addition of a small amount of pure (R)-alcohols increased the 5-value of kinetic resolution and, moreover, the effect disappeared quickly. The reason is probably that the alcohol moves into the active site where it is esterified. A future goal is to find an additive that can bind irreversibly to this unknown allosteric site, thus causing a lasting effect. 

W. H. Pirkle, The nonequivalence of physical properties of enantiomers in Optically active solvents. Differences in nuclear magnetic resonance spectra. I, /. Am. Chem. Soc. 88 (1966), 1837. 

Figure 2.12 Reprinted with permission from J. Am. Chem. Soc., vol. 91 T. Williams R. G. Pitcher P. Bommer J. Gutzwiller M. Uskokovic, Diastereomeric Solute-Solute Interactions of Enantiomers in Achiral Solvents. Nonequivalence of the Nuclear Magnetic Resonance Spectra of Racemic and Optically Active Dihydroquinine , pages 1871-1872 (1969). Copyright 1969, American Chemical Society.

The enantiomer and the racemic compound possess different crystal structures, which correspond to different intermolecular interactions, as mentioned in Sec. 3. Therefore the enantiomer and the racemic compound exhibit different powder x-ray diffraction (PXRD) patterns, different infrared (IR) and Raman spectra, and different solid-state nuclear magnetic resonance (SSNMR) spectra. However, the opposite enantiomers give identical PXRD patterns, and identical IR, Raman, and SSNMR spectra. Consequently, the PXRD patterns and the above spectra of a conglomerate, which is a physical mixture of opposite enantiomers, are identical to that of the pure enantiomers. In contrast, the diffraction pattern and the various corresponding spectra of the racemic compound usually differ significantly from those of the pure enantiomers. Therefore the type of racemate can be easily determined by comparing the diffraction patterns or the various spectra of the racemic species with that of one of the pure enantiomers (Figs. 3 5). The enantiomeric composition in a racemic mixture may be determined by PXRD, or by IR or SSNMR spectroscopy. Quantitative PXRD has been applied to determine the relative... 

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