Pure Shift

The concepts of pure-shift NMR and time-shared NMR are merged in a single experiment. A ¹³C/¹⁵N time-shared version of the real-time BIRD-based broadband homodecoupled HSQC experiment is described. This time-efficient approach affords simultaneously ¹H-¹³C and ¹H-¹⁵N pure-shift HSQC spectra in a single acquisition, while achieving substantial gains in both sensitivity and spectral resolution. We also present a related ¹³C/¹⁵N-F2-coupled homodecoupled version of the CLIP-HSQC experiment for the simultaneous measurement of ¹J_CH and ¹J_NH from the simplified doublets observed along the direct dimension. Finally, a novel J-resolved HSQC experiment has been designed for the simple and automated determination of both ¹J_CH/¹J_NH from a 2D J-resolved spectrum.

A ¹H‐¹H total correlation spectroscopy (TOCSY) experiment incorporating ¹³C multiplicity information is proposed. In addition, broadband ¹H homodecoupling in the indirect dimension can be implemented using a perfect BIRD module that affords exclusive ¹H chemical shift evolution with full decoupling of all heteronuclear and homonuclear (including ²J_HH) coupling constants. As a complement to the normal TOCSY and the recent PSYCHE‐TOCSY experiments, this novel multiplicity‐edited TOCSY experiment distinguishes between CH/CH₃ (phased up) and CH₂ (phased down) cross‐peaks, which facilitates resonance analysis and assignment.

Covariance processing is a versatile processing tool to generate synthetic NMR spectral representations without the need to acquire time-consuming experimental datasets. Here we show that even experimentally prohibited NMR spectra can be reconstructed by introducing key features of a reference 1D CHn-edited spectrum into standard 2D spectra. This general procedure is illustrated with the calculation of experimentally infeasible multiplicity-edited pure-shift NMR spectra of some very popular homonuclear (ME-psCOSY and ME-psTOCSY) and heteronuclear (ME-psHSQC-TOCSY and ME-psHMBC) experiments.

The current Pros and Cons of a processing protocol to generate pure chemical shift NMR spectra using Generalized Indirect Covariance are presented and discussed. The transformation of any standard 2D homonuclear and heteronuclear spectrum to its pure shift counterpart by using a reference DIAG spectrum is described. Reconstructed pure shift NMR spectra of NOESY, HSQC, HSQC-TOCSY and HSQMBC experiments are reported for the target molecule strychnine.

The combination of spectral aliasing and pure shift HSQC experiments represents an excellent routine tool for NMR enantiodifferentiation studies, yielding simultaneous ¹H and ¹³C enantiodifferentiated data (ΔΔδ(¹H) and ΔΔδ(¹³C)) in short times and with high digital resolution and signal dispersion for both ¹H and¹³C nuclei. Its use increases significantly the probability to detect an enantiodifferentiated nucleus since more signals are observed (¹H and ¹³C nuclei), overlapping problems of common 1D ¹H experiments are overcome, and poor enantiodifferentiation in 1D experiments can now be detected, allowing the study of cases abandoned in the past for reasons of poor enantioresolution and/or long experimental times. Alternatively, aliased long-range heteronuclear correlation experiments can be used to measure accurately such ΔΔδ values for quaternary carbons. The method is compatible with other heteronuclei and with the use of other chiral auxiliaries, and it can be of special interest for chiral metabonomic studies, where chiral molecules in complex mixtures are enantiodifferentiated and small chemical shifts need to be resolved in overcrowded spectra.

The implementation of the HOmodecoupled Band-Selective (HOBS) technique in the conventional Inversion-Recovery and CPMG-based PROJECT experiments is described. The achievement of fully homodecoupled signals allows the distinction of overlapped ¹H resonances with small chemical shift differences. It is shown that the corresponding T₁ and T₂ relaxation times can be individually measured from the resulting singlet lines using conventional exponential curve-fitting methods.

A frequency-selective 1D H-1 nuclear magnetic resonance (NMR) experiment for the fast and sensitive determination of chemical-shift differences between overlapped resonances is proposed. The resulting fully homodecoupled H-1 NMR resonances appear as resolved 1D singlets without their typical J(HH) coupling constant multiplet structures. The high signal dispersion that is achieved is then exploited in enantiodiscrimination studies by using chiral solvating agents.

An NMR method to enhance the sensitivity and resolution in band-selective long-range heteronuclear correlation spectra is proposed. The excellent in-phase nature of the seIHSQMBC experiment allows that homonuclear and/or heteronuclear decoupling can be achieved in the detected dimension of a 2D multiple-bond correlation map, obtaining simplified cross-peaks without their characteristic fine J multiplet structure. The experimental result is a resolution improvement while the highest sensitivity is also achieved. Specifically, it is shown that the H-1-homodecoupled band-selective (HOBS) HSQMBC experiment represents a new way to measure heteronuclear coupling constants from the simplified in-phase doublets generated along the detected dimension.

An NMR pulse scheme that provides full sensitivity in homodecoupled band‐selective NMR spectroscopy experiments is proposed (see figure). The easy implementation of this HOBS scheme as a general building block into a great variety of multidimensional NMR experiments leads to pure‐shift spectra with enhanced resolution and with the maximum attainable sensitivity.

A novel strategy to enhance the experimental sensitivity in spatially encoded NMR experiments has been developed. The use of a multiple‐frequency modulated pulse applied simultaneously to an encoding gradient can afford a substantial sensitivity gain with respect to single‐slice selected experiments