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Sunday, 23 August 2015

Proton NMR in Chiral Liquid Crystals

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Proton NMR in Chiral Liquid Crystals

 Nuclear Magnetic Resonance is a particularly well suited tool to study molecules which are dissolved in liquid crystals (1) : whereas intermolecular interactions from the spin Hamiltonian are averaged to zero by the translational and rotational diffusion of organic molecules from the mesophase, anisotropic intramolecular interactions are only partially averaged by molecular dynamics and, in the case of a uniaxial phase, reduced to a single – order sensitive – value for every molecule in the sample.(2).
 
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 These anisotropic measurements (mainly dipolar or quadrupolar couplings, or even chemical shift anisotropy which is weaker) have been successfully used to probe both the structure and the dynamics of molecules solvated in liquid crystals, and have notably led to the quantization of the difference in orientation between enantiomers diluted in a chiral liquid crystal, which results from diastereomeric interactions between the solute and the anisotropic solvent : the best results so far have been obtained using a lyotropic liquid crystal composed of poly-(γ-benzyl)-L-glutamate (PBLG) dissolved in various -non denaturing- organic solvents. This chiral differentiation process can be monitored through either 2H - {1H}, 13C - {1H}, 1H coupled 13C, or even natural abundance 2H - {1H} NMR spectra.(3-6)
 
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 However, because of numerous long-range dipolar couplings, proton spectra of enantiomers, though resulting from the most sensitive experiments, are usually overcrowded, and coupling fine structures are generally not resolved, which makes proton NMR useless as such in that field.
 In this context, our group has been working for years now on the simplification of the proton spectra of enaniomeric mixtures dissolved in chiral, liquid crystalline solvents. Below are presented some applications of our latest developments that have led to a simplification - and an acceleration - of the analysis of such data.
 

Application of SERF Spectroscopy to the Visualization of Enantiomers

 Our group is studying in what extent it is possible to simplify proton spectra, and enhance their resolution, to a point where the accurate measurement of enantiomeric excesses is reachable. We have shown how the use of homonuclear selective refocusing 2D NMR experiments (SERF), which was initially developed by Fäcke and Berger (7), and extensively studied since then, allows us to extract the coupling between proton spins at given resonance frequencies, out of their whole coupling network, in small chiral organic compounds. (8).
 
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 We show that it is possible to apply this approach to oriented samples, and increase the quality of the resulting spectra by optimizing the selective excitation and refocusing pulses, as well as the phase and gradient cyclings of this SERFph pulse sequence. (9)

Spin-Spin Coupling Edition in Chiral Liquid Crystal NMR Solvent

 We have applied the concept of a sample spatial frequency encoding to the analysis of enantiomeric mixtures dissolved in a chiral liquid crystal. We have run a G-SERFph (for phaseable Gradient encoded homonuclear SElective ReFocusing spectroscopy) experiment(10) on a model enantiomeric organic compound (propylene oxide dissolved in PBLG/CDCl3).
 
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  This approach, which consists in handling selectively each coupling in separate cross sections of the sample, is applied to the visualization of enantiomers dissolved in a chiral liquid crystalline phase. and we observe on the resulting spectrum an edition of multiplets which all involve the selected proton spin.
 
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 These multiplets appear at the resonance frequencies from every other protons to which it is coupled: we show that this pulse sequence allows the observation of enantiomeric discrimination between both enantiomers dissolved in the PBLG/CDCl3 chiral liquid crystalline phase.(11)
 We also evaluate the robustness of this pulse sequence when it is used to probe fully coupled systems, through an analysis of the experimental artifacts that may be generated. We show that the signals that arise from pulse miscalibrations, or a difference in selectivity between spatially encoded excitation and refocusing pulses, do not contribute to the overall spectrum since they are removed by gradient selection. Only one kind of artifact, in addition to the desired signal, actually follows the defined magnetization pathways and appears on the overall spectrum (this artifact does not hinder the coupling network measurement). Interestingly, from all the artifacts that could be expected,our analysis indicates that the biggest artifacts which can be observed on this sample, are actually mainly due to a second-order coupling effect.

Application of δ-Resolved Spectroscopy to Probe Proton Chemical Shift Anisotropy

 We have applied an experiment, which was initially implemented by Zangger and Sterk (12) for the indirect acquisition of proton broadband homodecoupled spectra, to the visualisation of the differences in proton chemical shift anisotropy between enantiomers which are interacting with a chiral environment. We have implemented an enhanced -phased- version of this pulse sequence: the resulting 2D δ-resolved spectra allow to discriminate enantiomers when the variation of the proton chemical shift anisotropy is measurable.
 
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 We have used an enhanced pulse sequence of this "δ-resolved" experiment to probe two chiral differentiation processes. Firstly, we use a lanthanide complex as a chiral shift reagent, and we probe its interaction with racemic isoborneol:
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 Secondly, we exploit the differential ordering effect on enantiomers of butynol of a chiral liquid crystalline solvent composed of Poly-(γ-Benzyl)-L-Glutamate dissolved into deuterated chloroform (PBLG/CDCl3):
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 For each sample, within one single 2D δ-resolved spectrum, we show that it is possible to probe the chiral differentiation process through every proton chemical shift where the variation in the chemical shift between each enantiomer is detectable.(13)

References

(1) Dong, R. Y., Nuclear Magnetic Resonance of Liquid Crystals (Partially Ordered Systems), Springer-Verlag Berlin, 1994, Ed. Springer-Verlag.
(2) Emsley, J.W., Nuclear Magnetic Resonance of Liquid Crystals, Kluwer Academic Publishers, 1984, D Reidel Pub Co.
(3) Merlet, D.; Ancian, B.; Courtieu, J.; Lesot, P., 1999, J. Am. Chem. Soc., 121, (22), 5249
(4) Sarfati, M.; Courtieu, J.; Lesot, P., Chem. Comm. 2000, (13), 1113-1114.
(5) Canet, I.; Courtieu, J.;Loewenstein, A.; Meddour, A.; Péchiné, J.M., 1995, J. Am. Chem. Soc., 117, 6520
(6) Meddour, A.; Berdague, P.; Hedli, A.; Courtieu, J.; Lesot, P., 1997, J. Am. Chem. Soc., 119, 4502
(7) Fäcke, T. and Berger, S., J. Magn. Reson. 1995, 113, 114-116.
(8) Béguin, L. ; Courtieu, J. ; Ziani, L. ; Merlet, D., Magn. Reson. Chem. 2006, (44), 1096-1101.
(9) Béguin, L., Giraud, N., Ouvrard, JM., Courtieu, J. and Merlet, D. J. Magn. Res. 2009.
(10) Giraud, N., Béguin, L., Courtieu, J. and Merlet, D., Ang. Chem. Int. Ed. 49 (20): 3481-3484, 2010
(11)  Merlet, D., Beguin, L., Courtieu, J. & Giraud, N.*,J. Magn. Res. 209 (2): 315-322 (2011)
(12) Zangger, K. and Sterk., H., J. Magn. Reson. 1997, 124, 486-489.
(13) Giraud, N., Joos, M., Courtieu, J. and Merlet, D., Magn. Res. Chem. 2009.

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