A General Method for Extracting Individual Coupling Constants from Crowded 1H NMR Spectra

Abstract Couplings between protons, whether scalar or dipolar, provide a wealth of structural information. Unfortunately, the high number of 1H‐1H couplings gives rise to complex multiplets and severe overlap in crowded spectra, greatly complicating their measurement. Many different methods exist for disentangling couplings, but none approaches optimum resolution. Here, we present a general new 2D J‐resolved method, PSYCHEDELIC, in which all homonuclear couplings are suppressed in F 2, and only the couplings to chosen spins appear, as simple doublets, in F 1. This approaches the theoretical limit for resolving 1H‐1H couplings, with close to natural linewidths and with only chemical shifts in F 2. With the same high sensitivity and spectral purity as the parent PSYCHE pure shift experiment, PSYCHEDELIC offers a robust method for chemists seeking to exploit couplings for structural, conformational, or stereochemical analyses.

[1]  M. Foroozandeh,et al.  Reports of meetings , 1974 .

[2]  Richard R. Ernst,et al.  Homonuclear broad band decoupling and two-dimensional J-resolved NMR spectroscopy , 1976 .

[3]  G. Bodenhausen,et al.  NMR spectra of some simple spin systems studied by two-dimensional fourier transformation of spin echoes , 1978 .

[4]  J. Keeler,et al.  Comparison and evaluation of methods for two-dimensional NMR spectra with absorption-mode lineshapes , 1985 .

[5]  S. Berger,et al.  SERF, a New Method for H,H Spin-Coupling Measurement in Organic Chemistry , 1995 .

[6]  K. Zangger,et al.  Homonuclear Broadband-Decoupled NMR Spectra , 1997 .

[7]  R. Freeman,et al.  Proton Chemical-Shift Spectra , 1997 .

[8]  W. A. Thomas.  Unravelling molecular structure and conformation—the modern role of coupling constants , 1997 .

[9]  A. J. Shaka,et al.  Improved Broadband Inversion Performance for NMR in Liquids , 2001 .

[10]  J. Courtieu,et al.  Simplification of the 1H NMR spectra of enantiomers dissolved in chiral liquid crystals, combining variable angle sample spinning and selective refocusing experiments , 2006, Magnetic resonance in chemistry : MRC.

[11]  J. Keeler,et al.  Two-dimensional J-spectra with absorption-mode lineshapes. , 2007, Journal of magnetic resonance.

[12]  G. Morris.  Two‐Dimensional J‐Resolved Spectroscopy , 2007 .

[13]  B. Luy.  Adiabatic z-filtered J-spectroscopy for absorptive homonuclear decoupled spectra. , 2009, Journal of magnetic resonance.

[14]  G. Kummerlöwe,et al.  Residual dipolar couplings as a tool in determining the structure of organic molecules , 2009 .

[15]  J. Courtieu,et al.  Improvements to selective refocusing phased (SERFph) experiments. , 2009, Journal of magnetic resonance.

[16]  Christofer Lendel,et al.  3D J-resolved NMR spectroscopy for unstructured polypeptides: fast measurement of 3JHNHα coupling constants with outstanding spectral resolution , 2009, Journal of biomolecular NMR.

[17]  A. Makriyannis,et al.  The Conformations of 17β-Estradiol (E2) and 17α-Estradiol as Determined by Solution NMR. , 2010, Tetrahedron letters.

[18]  Mathias Nilsson,et al.  Pure shift 1H NMR: a resolution of the resolution problem? , 2010, Angewandte Chemie.

[19]  J. Courtieu,et al.  Nuclear magnetic resonance using a spatial frequency encoding: application to J-edited spectroscopy along the sample. , 2010, Angewandte Chemie.

[20]  M. Nilsson,et al.  Simple proton spectra from complex spin systems: pure shift NMR spectroscopy using BIRD. , 2011, Angewandte Chemie.

[21]  C. Thiele,et al.  Determining the Stereochemistry of Molecules from Residual Dipolar Couplings (RDCs) , 2012 .

[22]  K. Zangger,et al.  Disentangling scalar coupling patterns by real-time SERF NMR. , 2014, Chemical communications.

[23]  N. Suryaprakash,et al.  Quick re-introduction of selective scalar interactions in a pure-shift NMR spectrum. , 2014, Chemical communications.

[24]  Mathias Nilsson,et al.  Ultrahigh-Resolution NMR Spectroscopy , 2014, Angewandte Chemie.

[25]  R. W. Adams,et al.  Pure Shift NMR Spectroscopy , 2014 .

[26]  K. Zangger,et al.  Pure shift NMR. , 2015, Progress in nuclear magnetic resonance spectroscopy.

[27]  S. Robin,et al.  Pushing the limits of signal resolution to make coupling measurement easier. , 2015, Chemical communications.

[28]  D. Bonnaffé,et al.  Fully resolved NMR correlation spectroscopy. , 2015, Chemistry.

[29]  Ajay Verma,et al.  Real-time band-selective homonuclear proton decoupling for improving sensitivity and resolution in phase-sensitive J-resolved spectroscopy. , 2015, Chemphyschem : a European journal of chemical physics and physical chemistry.

[30]  M. Foroozandeh,et al.  Measuring couplings in crowded NMR spectra: pure shift NMR with multiplet analysis. , 2015, Chemical communications.