Time-Efficient NMR
P. Nolis, K. Motiram-Corral, M. Pérez-Trujillo and T. Parella
ChemPhysChem, 20, 356-360 (2019). DOI
Interleaved Dual NMR Acquisition of Equivalent Transfer pathways in TOCSY and HSQC experiments
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.
P. Nolis, K. Motiram-Corral, M. Pérez-Trujillo and T. Parella
J. Magn. Reson, 298, 23-30 (2019). DOI
Broadband Homodecoupled Time-Shared 1H-13C and 1H-15N HSQC Experiments
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.
P. Nolis and T. Parella
Magn. Reson. Chem., 57, 85-94 (2019). DOI
Practical aspects of the simultaneous collection of COSY and TOCSY spectra
The practical aspects of some NMR experiments designed for the simultaneous acquisition of 2D COSY and 2D TOCSY spectra are presented and discussed. Several techniques involving afterglow‐based, coherence transfer pathway (CTP)‐based, and NMR by Ordered Acquisition using 1H‐detection (NOAH)‐based strategies for the collection of different free‐induction signal decays (FIDs) within the same scan are evaluated and compared. These methods offer a faster recording of these spectra in small‐molecule NMR when sensitivity is not a limiting factor, with a reduction in spectrometer time about 45–60% when compared with the conventional sequential acquisition of the parent experiments. It is also shown how the optimized design of an extended three‐FID approach yields one COSY and two TOCSY spectra simultaneously by combining CTP and NOAH principles in the same experiment, affording substantial sensitivity enhancements per time unit.
P. Nolis, K. Motiram-Corral, M. Pérez-Trujillo and T. Parella
J. Magn. Reson., 300, 1-7 (2019). DOI
Simultaneous acquisition of two 2D HSQC spectra with different 13C spectral widths
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.
K. Motiram-Corral, M. Pérez-Trujillo, P Nolis and T. Parella
Chem. Comm., 54, 13507-13510 (2018). DOI
Implementing one-shot multiple-FID acquisition into homonuclear and heteronuclear NMR experiments
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 presented. As a proof of concept, a set of novel COSY, TOCSY and HMBC experiments are reported as a time-efficient solution in small-molecule NMR spectroscopy.
P. Nolis, M. Pérez-Trujillo and T. Parella
Angew. Chem. Intl. Ed., 46, 7495-7497 (2007). DOI
Multiple-FID Acquisition of Complementary HMBC Data
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 %.
M. Pérez-Trujillo, P.Nolis, W. Bermel, and T. Parella
Magn. Reson. Chem., 45, 325-329 (2007). DOI
Optimizing sensitivity and resolution in time-shared NMR experiments
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.
P.Nolis and T. Parella
J. Biomol. NMR, 37, 65-77 (2007). DOI.
Simultaneous a/b-spin-state selection for 13C and 15N from a time-shared HSQC-IPAP experiment
Two novel HSQC-IPAP approaches are proposed to achieve α/β spin-state editing simultaneously for 13C and 15N in a single NMR experiment. The pulse schemes are based on a time-shared (TS) 2D 1H,13C/1H,15N-HSQC correlation experiment that combines concatenated echo elements for simultaneous J(CH) and J(NH) coupling constants evolution, TS evolution of 13C and 15N chemical shifts in the indirect dimension and heteronuclear α/β-spin-state selection by means of the IPAP principle. Heteronuclear α/β-editing for all CH n (n = 1–3) and NH n (1–2) multiplicities can be achieved in the detected F2 dimension of a single TS-HSQC-F2-IPAP experiment. On the other hand, an alternative TS-HSQC-F1-IPAP experiment is also proposed to achieve α/β-editing in the indirect F1 dimension. Experimental and simulated data is provided to evaluate these principles in terms of sensitivity and performance simultaneously on backbone and side-chain CH, CH2, CH3, NH, and NH2 spin systems in uniformly 13C/15N-labeled proteins and in small natural-abundance peptides.
M. Pérez-Trujillo, P. Nolis, and T. Parella
Org. Letters, 9, 29-32 (2007). DOI
CN-HMBC: A powerful NMR technique for the simultaneous detection of long-range 1H,13C and 1H,15N connectivities
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.
P.Nolis, M. Pérez-Trujillo, and T. Parella
Magn. Reson. Chem., 44, 1031-1036 (2006). DOI
Time-sharing evolution and sensitivity enhancements in 2D HSQC-TOCSY and HSQMBC experiments
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.