Roberto R. Gil (Carnegie Mellon-Pittsburg)
Isotropic/Anisotropic NMR editing by resolution-enhanced NMR spectroscopy
Modern resolution‐enhanced NMR techniques can monitor the in situ discrimination of co‐existing isotropic and anisotropic contributions of small molecules dissolved in weakly aligning PMMA/CDCl3 media. The simultaneous sign‐sensitive determination of accurate Δδiso–aniso(1H), Δδiso–aniso(13C) and/or isotropic 1JCH and anisotropic 1TCH coupling constants (and consequently 1H‐13C residual dipolar couplings and 1H/13C residual chemical shift anisotropies) can be performed from spectral‐aliased heteronuclear single‐quantum correlation spectra.
N. Marcó, R. R. Gil and T. Parella
Magn. Reson. Chem, 55, 525-529 (2017). DOI
Structural discrimination from in-situ measurement of 1DCH and 2DHH residual dipolar coupling constants
A fast RDC-assisted strategy involving the simultaneous determination of scalar and total coupling constants from a single 1JCH/2JHH-resolved NMR spectrum is reported. It is shown that the concerted use of the directly measured 1DCH (for all CHn multiplicities) and 2DHH residual dipolar couplings allows an on-the-fly assignment of diastereotopic CH2 protons, as well as of an efficient discrimination between all eight possible diastereoisomeric structures of strychnine, which contains six stereocenters.
N. Marcó, P. Nolis, R.R. Gil and T. Parella
J. Magn. Reson., 282,18-26 (2017). DOI
2J(HH)-resolved HSQC: Exclusive determination of geminal proton-proton coupling constants
The measurement of two-bond proton-proton coupling constants (2JHH) in prochiral CH2 groups from the F2 dimension of 2D spectra is not easy due to the usual presence of complex multiplet J patterns, line broadening effects and strong coupling artifacts. These drawbacks are particularly pronounced and frequent in AB spin systems, as those normally exhibited by the pair of diastereotopic CH2 protons. Here, a novel 2JHH-resolved HSQC experiment for the exclusive and accurate determination of the magnitude of 2JHH from the doublet displayed along the highly-resolved indirect F1 dimension is described. A pragmatic 2JHH NMR profile affords a fast overview of the full range of existing 2 J HH values. In addition, a 2JHH/d(13C)-scaled version proves to be an efficient solution when severe signal overlapping complicate a rigorous analysis. The performance of the method is compared with other current techniques and illustrated by the determination of challenging residual dipolar 2D(HH) coupling constants of small molecules dis- solved in weakly orienting media.
N. Marcó, A.A. Souza, P. Nolis, C. Cobas, R.R. Gil and T. Parella
J. Org. Chem, 82, 2040-2044 (2017). DOI
1JCH NMR Profile: Identification of key structural features and functionalities by visual observation and direct measurement of one-bond proton-carbon coupling constants
A user-friendly NMR interface for the visual and accurate determination of experimental one-bond proton-carbon coupling constants (1JCH) in small molecules is presented. This intuitive 1JCH profile correlates directly to δ(1H), and 1JCH facilitates the rapid identification and assignment of 1H signals belonging to key structural elements and functional groups. Illustrative examples are provided for some target molecules, including terminal alkynes, strained rings, electronegative substituents, or lone-pair-bearing heteronuclei.
N. Marcó, A.A. Souza, P. Nolis, R.R. Gil and T. Parella
J. Magn. Reson, 276, 37-42 (2017). DOI
Perfect 1JCH-resolved HSQC: Efficient measurement of one-bond proton-carbon coupling constants along the indirect dimension
A versatile 1JCH-resolved HSQC pulse scheme for the speedy, accurate and automated determination of one-bond proton-carbon coupling constants is reported. The implementation of a perfectBIRD element allows a straightforward measurement from the clean doublets obtained along the highly resolved F1 dimension, even for each individual 1JCHa and 1JCHb in diastereotopic HaCHb methylene groups. Real-time homodecoupling during acquisition and other alternatives to minimize accidental signal overlapping in overcrowded spectra are also discussed.
A. A. Souza, R.R. Gil and T. Parella
J. Magn. Reson., 282, 54-61 (2017). DOI
Highly resolved HSQC experiments for the fast and accurate measurement of homonuclear and heteronuclear coupling constants
A number of J-upscaled NMR experiments are currently available to measure coupling constants along the indirect F1 dimension of a 2D spectrum. A major drawback is the limited F1 digital resolution that requires long acquisition times in order to achieve reasonably accurate measures. Here is shown how high levels of F1 digital resolution in a multiple-purpose HSQC experiment can be easily achieved by implementing a general J/d-scaling strategy. In particular, a set of new J-resolved HSQC experiments is presented for a faster and much more accurate J determination in small molecules. Several options and practical aspects are discussed and exemplified by measuring the magnitude and/or the sign of several homo- and heteronuclear coupling constants in one shot.
L. Castañar, M. García, E. Hellemann, P. Nolis, R.R. Gil and T. Parella
J. Org. Chem., 81, 11126-11131 (2016). DOI
One-Shot determination of residual dipolar couplings. Application to the structural discrimination of small molecules containing multiple stereocenters
A novel approach for the fast and efficient structural discrimination of molecules containing multiple stereochemical centers is described. A robust J-resolved HSQC experiment affording highly resolved 1JCH/1TCH splittings along the indirect dimension and homodecoupled 1H signals in the detected dimension is proposed. The experiment enables in situ distinction of both isotropic and anisotropic components of molecules dissolved in compressed PMMA gels, allowing a rapid and direct one-shot determination of accurate residual dipolar coupling constants from a single NMR spectrum.