Skriv ut originalartikkelen og bruk en dag på å lese den langsomt om du har tid. Dette var værre en det så ut til å begynne med. Dessuten ganske lang artikkel så den som legger ut dette lot være å kopiere alle figurene. Correlation 2D-NMR experiments involving both 13C and 2H isotopes in oriented media: methodological developments and analytical applications† Philippe Lesot1,*, Olivier Lafon2 andPhilippe Berdagué1 Article first published online: 10 SEP 2014 DOI: 10.1002/mrc.4118 Magnetic Resonance in Chemistry Special Issue: NMR of Liquid Crystals Volume 52, Issue 10, pages 595–613, October 2014 Abstract Correlation 2D-NMR experiments for 13C and 2H isotopes turn out to be powerful methods for the assignment of the quadrupolar doublets in the 2H NMR spectra of isotopically modified (polydeuterated or perdeuterated) or unmodified solutes in homogeneously oriented solvents, such as thermotropic systems or lyotropic liquid crystals. We review here the different pulse sequences, which have been employed, their properties, and their most salient applications. These 2D-NMR sequences have been used for (i) 13C–2H correlation with and without 1H relay and (ii) 2H–2H correlation with 13C relay. The 13C–2H correlation experiments without 1H relay have been achieved for specifically deuterated or non-selectively deuterated analytes, but also more recently for isotopically unmodified ones thanks to the high sensitivity of very high-field NMR spectrometers (21.1 T) equipped with cryogenic probes. The 13C–2H correlation 2D-NMR experiments are especially useful for the assignment of overcrowded deuterium spectra because the 2H signals are correlated to 13C signals, which benefit from a much larger dispersion of chemical shifts. In this contribution, particular attention will be paid to the use of correlation 2D-NMR experiments for 2H and 13C nuclei in weakly aligning, polypeptide oriented chiral solvents, because these methods are useful and original tools for enantiomeric and enantiotopic analyses. Deuterium NMR spectroscopy on deuterated molecules or at natural abundance level (1.55 × 10−2% compared to 1H) noted thereafter natural abundance deuterium (NAD) is a powerful tool for a broad range of applications in (bio)chemistry. This includes the following: (i) the elucidation of chemical reaction mechanisms,[1, 2] (ii) the determination of metabolic pathways,[3-6] (iii) the identification of geographical or botanical origin and the fight against counterfeiting,[7, 8] (iv) the study of orientational order in anisotropic media (liquid crystals, membranes, and confined or stretched polymer chains),[9-16] and (v) the analysis of atom-scale dynamics in various systems, including biomolecules and advanced materials.[17-19] Recently, 2H NMR using chiral anisotropic solvents has been proposed as an efficient and versatile technique for stereochemical analysis.[20, 21] Thus, this technique has been successfully applied: (i) discriminate enantiomers, including isotopic ones, and enantiotopic elements in prochiral molecules,[22] (ii) to measure enantiomeric excesses (ee) associated with asymmetric synthesis or biosynthetic pathways,[23] (iii) to determine the relative[24] and absolute[25] configuration of small molecules, (iv) to study conformational exchange,[26, 27] and (v) to measure the isotopic profile of natural products.[28, 29] Interestingly, 2H nuclei have a spin I = 1 and, hence, a quadrupolar electric moment, eQD, with e the elementary charge and QD = 0.286 fm2. This quadrupolar moment is small, and hence, 2H NMR spectra recorded in solutions or in mesophases benefit from high resolution. Furthermore, the low gyromagnetic ratio of 2H isotope (γ(2H) = 0.153γ(1H)) leads to small 2H–2H dipolar coupling constants, even in perdeuterated solids.[30] Consequently, 2H NMR spectra of mesophases or solids often exhibit higher resolution than the 1H spectra.[31] In anisotropic fluids and solids, the 2H spectra are dominated by the quadrupolar interaction originating from the quadrupolar moment and the electric field gradient at the position of the 2H nucleus. This interaction provides valuable information on molecular orientational ordering and dynamics. The flip side of the low value of γ(2H) is the weaker sensitivity of 2H NMR compared to 1H NMR. Nevertheless, the continuous improvements in NMR instrumentation and methodology (high magnetic field, cryogenic probe, advanced electronic, fast processing, …) have enabled the acquisition of NAD spectra in steadily lower concentration, in both isotropic and anisotropic fluids as well as in solids, even if the natural abundance of 2H is only 1.55 × 10−2%.[20, 21, 32] The assignment of one-dimensional (1D) 2H NMR spectra of polydeuterated or isotopically unmodified solutes (NAD NMR) is often difficult, owing to the limited range of 2H chemical shifts (20 ppm). Furthermore, this range in Hertz is only 15% of 1H one because γ(2H) = 0.153γ(1H). The assignment is even more challenging in chiral oriented media because the spectral enantiodiscrimination increases significantly the number of 2H signals. Various multidimensional (nD) NMR experiments have been proposed to facilitate the assignment of anisotropic 2H signals. These NMR experiments include the following: (i) 2H autocorrelation two-dimensional (2D) and three-dimensional (3D) methods, which correlate the two components of the quadrupolar doublets and permit to assign them on the basis of the 2H chemical shifts,[33-36] (ii) 2H homonuclear correlation 2D experiments via 2H–2H scalar (nJDD) and dipolar (nDDD) couplings[37-39] or with 13C relay,[40] and (iii) 13C–2H correlation 2D experiments, which correlate the 2H signal with that of the covalently bonded 13C nucleus and thus allow the assignment of 2H signals on the basis of 13C chemical shifts.[1-5, 17, 18, 31, 38, 41-56] The assignment in 2H autocorrelation and homonuclear correlation methods is based on the 2H chemical shifts, which correspond to a narrow frequency range, as explained earlier. Furthermore, 2H–2H couplings are often too weak to produce visible correlation peaks, especially for weakly aligned solutes or for NAD experiments. 2H–13C correlation 2D experiments benefit from (i) the larger dispersion of 13C chemical shifts (200 ppm), which is about tenfold larger in parts per million than that of 2H chemical shifts and (ii) the non-negligible 2H–13C heteronuclear (1JCD and 1DCD) couplings between covalently bonded nuclei. Given the low natural abundance of isotopomers containing both 2H and 13C nuclei (1.55 10−2% × 1.1%), 2H–13C correlation 2D spectra have been mainly acquired for deuterated compounds. However, the first acquisitions of 2H–13C correlation 2D spectra of isotopically unmodified solutes dissolved in solutions or in weakly ordering liquid crystals have been recently achieved using high-field NMR spectrometer equipped with a cryogenic probe.[48] 2H–13C correlation 2D-NMR experiments have been employed for solutes dissolved in isotropic liquids[1-5] or weakly aligned in chiral liquid crystals[38, 45, 46, 48] as well as for mesogenic molecules of thermotropic liquid crystals[41-44, 49] and for the solid state of aminoacids, peptides, and proteins.[17, 18, 31, 50-56] For isotropic liquids, 2H–13C 2D correlation has been achieved using 2H [RIGHTWARDS ARROW] 13C INEPT transfer[1-5, 57] because it is usually more sensitive than other methods, such as HMQC or HSQC.[4] Note also that 2H [RIGHTWARDS ARROW] 13C INEPT and DEPT 1D experiments as well as 2H [RIGHTWARDS ARROW] 13C and 13C [RIGHTWARDS ARROW] 2H cross-polarization (CP) ones using isotropic solvents have been reported in literature.[57-59] For liquid crystals and solids, 2H–13C correlation experiments have employed either 2H [RIGHTWARDS ARROW] 13C INEPT transfer,[38, 45-48] 13C [RIGHTWARDS ARROW] 2H [RIGHTWARDS ARROW] 13C HMQC scheme,[43, 44, 50, 52] 2H [RIGHTWARDS ARROW] 13C DAPT,[49] or 2H [RIGHTWARDS ARROW] 13C CP transfer.[17, 18, 31, 41, 42, 51, 53, 56] For strongly aligned compounds or solids, the CP transfer is rendered difficult by the intricate spin dynamics of 2H coherences in the presence of first-order quadrupolar interaction, which is about 170–210 kHz, and generally exceeds typical rf field strengths.[41, 42, 55, 60] For solids under MAS conditions, it has been shown that CP transfer employing a train of rotor-synchronized pulses on the 2H channel are more efficient, more robust, and requires lower rf field than those employing continuous rf irradiation.[55, 61] In this review, we present and discuss the correlation 2D experiments involving 2H and 13C isotopes in oriented media. We especially focus on the use of these NMR methods in weakly orienting chiral media. Conclusion NMR in anisotropic media has proven to be a powerful tool for the structural analysis of complex small organic molecules.[98-100] Among magnetically active nuclei, deuterons provide remarkable nuclear spies that can be used for numerous and original analytical applications ranging from the structural or stereochemical analysis to natural isotope fractionation. This quadrupolar nucleus of weak quadrupolar moment and ubiquitous in all organic molecules provides useful insights into the molecular orientational ordering and dynamics in anisotropic media and solids. Furthermore, it can now be detected in natural abundance by NMR experiments in a few hours. Various specifically designed NMR tools have been introduced in the last decade to facilitate the analysis of complex/overcrowded anisotropic 2H 1D-NMR spectra, using homonuclear or heteronuclear correlation experiments. In this contribution, we have presented a compendium of the correlation 2D-NMR experiments involving 2H and 13C nuclei in oriented media. In particular, we have described the experiments, which have been used in chiral oriented systems. The advent of very high-magnetic field spectrometers equipped with 2H cryogenic probes is expected to generalize the use of these analytical tools, which are now applicable for isotopically unmodified solutes dissolved in liquids or weakly ordering media. These correlation 2D experiments involving 2H and 13C nuclei will have implication for various fields, including organic chemistry, biochemistry, food sciences, pharmacology, catalysis, and material sciences.
Posted on: Mon, 10 Nov 2014 19:00:16 +0000
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