NMR Methodology
The development of new NMR and NMR related methodology allow the improvement of fundamental analytical parameters of the technique (signal to noise ratio, spectral resolution, spectral dispersion, detection limit ...), which broads its applications
Published works
Simultaneous acquisition of two 2D HSQC spectra with different 13C spectral widths
P Nolis, K Motiram-Corral, M Pérez-Trujillo, T Parella*
Journal of Magnetic Resonance, 2019, 300, 1-7. DOI
A time-efficient NMR strategy that involves the interleaved acquisition of two 2D HSQC spectra having different spectral widths in the indirect 13C dimension is presented. We show how the two equivalent coherence transfer pathways involved in sensitivity-enhanced HSQC experiments are managed selectively and detected separately in different FID periods within the same scan. The feasibility of this new SADA-HSQC (Spectral Aliasing in Dually Acquired HSQC) technique is demonstrated by recording simultaneously two complementary datasets, conventional and highly-resolved spectral-aliased 2D HSQC spectra, in a single NMR experiment. Combining the information from both datasets, accurate chemical shift determination and excellent signal dispersion is achieved in a unique measurement using only few t1 increments.
Interleaved Dual NMR Acquisition of Equivalent Transfer Pathways in TOCSY and HSQC Experiments
P Nolis, K Motiram-Corral, M Pérez-Trujillo, T Parella*
ChemPhysChem, 2019, 20, 356-360. DOI
A dual NMR data acquisition strategy to handle and detect two active equivalent transfer pathways is presented and discussed. We illustrate the power of this time‐efficient approach by collecting two different 2D spectra simultaneously in a single experiment: i) TOCSY or HSQC‐TOCSY spectra with different mixing times, ii) F2‐13C‐coupled and decoupled HSQC spectra, iii) conventional and pure‐shift HSQC spectra, or iv) complementary HSQC and HSQC‐TOCSY spectra.
Broadband homodecoupled time-shared 1H-13C and 1H-15N HSQC experiments
P Nolis, K Motiram-Corral, M Pérez-Trujillo, T Parella*
Journal of Magnetic Resonance, 2019, 298, 23-30. DOI
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 1JCH and 1JNH 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 1JCH/1JNH from a 2D J-resolved spectrum.
Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments
K Motiram-Corral, M Pérez-Trujillo, P Nolis,* T Parella*
Chemical communications, 2018, 54, 13507-13510. DOI
Multiple-Fid Acquisition (MFA) within the same scan is applied to acquire simultaneously multiple 2D spectra from a single NMR experiment. A discussion on the incorporation of the MFA strategy in several homonuclear and heteronuclear 2D pulse sequences is made. As proof of the concept, a set of novel COSY, TOCSY and HMBC experiments are presented as a time-efficient solution in small molecule NMR spectroscopy.
Simultaneous 1H and 13C NMR enantiodifferentiation from highly-resolved pure shift HSQC spectra
M. Pérez-Trujillo, L. Castañar, E. Monteagudo, L. T. Kuhn, P. Nolis, A. Virgili, R. T. Williamson, T. Parella*
Chemical communications, 2014, 50, 10214-10217. DOI
NMR enantiodifferentiation studies are greatly improved by the simultaneous determination of 1H and 13C chemical shift differences through the analysis of highly resolved cross-peaks in spectral aliased pure shift (SAPS) HSQC spectra. The determination of enantiomeric purity can be accomplished by NMR spectroscopy using a great variety of auxiliary chiral sources. Of these, chiral solvating agents (CSAs), such as the so-called Pirkle alcohol (PA) or cyclodextrins (CDs), have been widely used. They do not typically introduce significant line-broadening, the sample is easily prepared and the analysis is quickly performed by observing chemical shift differences (ΔΔδ) between the resulting diasteromeric complexes in conventional 1H NMR spectra. However, signal enantiodifferentiation using CSAs is not uniform for all protons and in many cases, low ΔΔδ values and signal overlap caused by complex multiplets lead to the lack of spectral signal dispersion that preclude a straightforward analysis. Alternatively, enantiodifferentiation using 13C NMR spectroscopy can be more advantageous because singlet signals are analyzed, although its routine use is limited by its low sensitivity.
Enantiodifferentiation through Frequency‐Selective Pure‐Shift 1H Nuclear Magnetic Resonance Spectroscopy
L. Castañar, M. Pérez‐Trujillo, P. Nolis, E. Monteagudo, A. Virgili, T. Parella*
ChemPhysChem, 2014, 15, 854-857. DOI
A frequency-selective 1D 1H nuclear magnetic resonance (NMR) experiment for the fast and sensitive determination of chemical-shift differences between overlapped resonances is proposed. The resulting fully homodecoupled 1H 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.
Multiple FID acquisition of complementary HMBC data
P. Nolis, M. Pérez‐Trujillo, T. Parella*
Angewandte Chemie International Edition, 2007, 46, 7495-7497. DOI
One experiment, four NMR spectra. By combining the principles of time-sharing evolution and multiple FID acquisition within the same scan, several fully complementary NMR spectra can be obtained in a single-shot acquisition. Four different HMBC and HMBC-relayed experiments (see spectra) can be carried out simultaneously for 13C and 15N at natural abundance, with a saving in measuring time of up to 75 %.
CN-HMBC: a powerful NMR technique for the simultaneous detection of long-range 1H, 13C and 1H, 15N connectivities
M. Pérez-Trujillo, P. Nolis, T. Parella*
Organic letters, 2007, 9, 29-32. DOI
A new one-shot NMR experiment (CN-HMBC) is proposed for the simultaneous acquisition of 2D 1H,13C and 1H,15N HMBC spectra. Important sensitivity enhancements (up to 41% simultaneously for both 13C and 15N) or time savings (about 50%) can be achieved when compared to the separate acquisition of individual HMBC spectra. The experiment is highly recommended for the complete structural analysis and simultaneous chemical shift assignments of protonated and nonprotonated 13C and 15N resonances in nitrogen-containing organic compounds.
Optimizing sensitivity and resolution in time‐shared NMR experiments
M. Pérez‐Trujillo, P. Nolis, W. Bermel, T. Parella*
Magnetic Resonance in Chemistry, 2007, 45, 325-329. DOI
An improved approach to optimize the overall sensitivity and the resolution requirements in the indirect dimension of 13C/15N time-shared (TS) NMR experiments is presented. A different data sampling acquisition procedure is applied for 13C and 15N in the indirect dimension, and a proper data recombination before conventional data processing allows a customized adjustment of spectral widths, number of scans and number of increments individually for 13C and 15N. The major benefit is an important improvement on the detection limits of the TS experiment that overcomes the lower sensitivity of 15N over 13C at natural abundance. We evaluate such enhancements from 2D TS-HMBC experiments recorded on a nitrogen-containing synthetic azole derivative of pharmaceutical interest.
Time-sharing evolution and sensitivity enhancements in 2D HSQC-TOCSY and HSQMBC experiments
P. Nolis, M. Pérez, T. Parella*
Magnetic Resonance in Chemistry, 2006, 44, 1031–1036. DOI
Modifications of time-shared (TS) HSQC-like experiments originally developed by Griesinger and co-workers (Sattler M, Maurer M, Schleucher J, Griesinger C. J. Biomol. NMR 1995; 5: 97) are proposed to extract different types of information from a single NMR pulse scheme. It is shown that simultaneous acquisition of 1H,13C and 1H,15N HSQC-TOCSY and HSQMBC experiments can afford experimental sensitivity enhancements of 20–40% with respect to the separate acquisition of individual 13C or 15N data. In addition, the incorporation of a number of independent editing elements can be easily used for different purposes, for instance, to assign unambiguously 1H, 13C, and 15N chemical shifts, to differentiate directly from relayed cross-peaks, or to measure simultaneously long-range proton–carbon and proton–nitrogen coupling constants. The suggested methodologies can be applied to many different classes of nitrogen-containing compounds and illustrative examples are provided for the peptide cyclosporine as a demonstration of the performance of such experiments.
