LR-HSQMBC versus LR-selHSQMBC: Enhancing the Observation of Tiny Long-Range Heteronuclear NMR Correlations

Motiram-Corral, Kumar; Nolis, Pau; Saurí, Josep; Parella, Teodor

doi:10.1021/acs.jnatprod.0c00058

Cited by 7 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and proved to be the best choice for detecting very weak long-range correlations. [4,9,[18][19][20][21][22][23] However, and despite the absence of J HH 0 -modulation our recent findings demonstrate that in LR-HSQC experiments, the intensity of the long-range cross peaks is influenced in an unwanted way by the magnitude and number of passive homonuclear proton-proton couplings J HH 0 . [24] In addition, there are two other, long known, disadvantages associated with LR-HSQC spectra: (i) The information density in LR-HSQC spectra due to the large number of detectable n J CH correlations can be too high and therefore confusing.…”

Section: Introductionmentioning

confidence: 55%

“…On the other hand, the very intense long-range responses and the associated one-bond responses of CH 3 (23) at δ = 0.91 ppm and of CH 3 (28,29) at δ = 0.86 and 0.865 ppm, with doublets in the 1 H spectrum, are clearly visible in the LR-HTQC spectrum (Figure 3) and only slightly less intense than in the LR-HSQC spectrum. The residual cross peaks in the LR-HTQC spectrum are equally or less intense compared to the corresponding cross peaks in the LR-HSQC spectrum (Figures 4 and 5).…”

Section: Cholesteryl Acetatementioning

confidence: 99%

“…The (singlet) resonances of CH 3 (1) at δ = 2.02 ppm, CH 3 (9) at δ = 1.01 ppm, and CH 3 (19) at δ = 0.67 ppm (Figure 5) exemplify the case of CH spin systems, whereas the (doublet) resonances of CH 3 (23) at δ = 0.91 ppm and CH 3 (28,29) at δ = 0.86 and 0.865 ppm illustrate the case of CHH' spin systems ( 3 J H23H22 = Hz, J H28H27 = 6.6 Hz). Clearly, as predicted, the long-range responses and the associated one-bond responses of the methyl groups 1 and 9 are completely suppressed or, for the CH 3 (19) resonance at δ = 0.67 ppm, at least significantly reduced.…”

Section: Cholesteryl Acetatementioning

confidence: 99%

“…Of note, selective and nonselective versions of the LR‐HSQMBC pulse sequence, a refocused variant of the LR‐HSQC experiment, have been recently proposed and proved to be the best choice for detecting very weak long‐range correlations. [ 4,9,18–23 ]…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

Bigler

Furrer

2020

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

Long-range heteronuclear single quantum correlation (LR-HSQC) experiments may be applied for detecting long-range correlations but suffer from two disadvantages, common to all heteronuclear long-range correlation experiments: (i) The information density in LR-HSQC spectra may be too high to be used directly without "filtering out" shorter range correlations, and (ii) often, substantial differences in intensity among cross peaks exist, potentially hampering the visualization of weak, often crucial cross peaks. In this contribution, we propose a modified LR-HSQC experiment, the LR-HTQC experiment (Long-Range Heteronuclear Triple Quantum Correlation) that partially solves the problems aforementioned. We show theoretically and experimentally that the LR-HTQC experiment removes the intense cross peaks of CH spin pairs, substantially reduces the medium intensity of cross peaks originating from CHH' spin systems, whereas the typically weak intensity of cross peaks of CHH'H 00 and C(H) n , n > 3 spin systems is less affected. Consequently, the LR-HTQC experiment affords simplified long-range heteronuclear shift correlation spectra and scales down large intensity differences among different types of cross peaks, although a certain general reduction of signal intensities has to be accepted.

show abstract

Section: Introductionmentioning

confidence: 55%

Section: Cholesteryl Acetatementioning

confidence: 99%

Section: Cholesteryl Acetatementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

Bigler

Furrer

2020

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

show abstract

“…To address these challenges, the usefulness of the LR-HSQMBC NMR experiment was evaluated. As the name indicates, LR-HSQMBC is a recently developed NMR experiment that provides long-range correlation data across 4-, 5-, and even 6-bond heteronuclear couplings [ 22 ], and it has been used to enhance the structure elucidation of hydrogen-deficient molecules [ 23 - 25 ]. The LR-HSQMBC spectrum of 1 ( Fig.…”

Section: Structure Elucidation Of 1-4mentioning

confidence: 99%

Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation

et al. 2021

View full text Add to dashboard Cite

A series of thielavins I, V, and Q ( 1-3 ) and the previously undescribed thielavin Z 8 ( 4 ) were isolated from cultures of a fungal Shiraia -like sp. (strain MSX60519) that were grown under a suite of media and light conditions, with enhanced biosynthesis noted using rice as a substrate with 12:12 h light:dark cycles. Conversely, oatmeal medium and continuous white LED light exposure negatively affected the production of these compounds, at least by strain MSX60519. The structure of 4 was determined using NMR spectroscopic data and mass fragmentation patterns. Of note, the utility of LR-HSQMBC and NOESY NMR experiments in the structural elucidation of these hydrogen-deficient natural products was demonstrated. Compounds 1-4 exhibited cytotoxic activity at the micromolar level against human breast, ovarian, and melanoma cancer cell lines.

show abstract

Advances in NMR‐Based Characterization of Drug Substances, Impurities, Degradants, and Drug Metabolites

Saurí

Reibarkh

Williamson

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

In the approximately 70 years since the first reports of experiments that led to what is now known as nuclear magnetic resonance or NMR spectroscopy, the technique has become the cornerstone of molecular structure characterization. From the isolation of strychnine to the confirmation of its complex structure in a total synthesis reported by Woodward consumed a century and a half. In contrast, using a modern 600 MHz NMR instrument equipped with a 1.7 mm MicroCryoProbe™, that task can now be accomplished in 24 hours, including the acquisition of 15 N chemical shift information on a few milligrams of sample. Such is the magnitude of the advances that have been made in the discipline. This article is not intended to make NMR spectroscopists out of a practicing medicinal chemistry; rather, the article is intended to acquaint the reader with recent advances in NMR techniques that are making it possible to successfully and unequivocally characterize ever increasingly more complex structures being synthesized in the laboratory as potential drug candidates or isolated from nature. Our goal was to augment the NMR knowledge of the medicinal chemist, better equipping him or her to more effectively interact with the NMR spectroscopy staff at the chemist's facility. The article begins with a discussion of new experimental methods that allow the acquisition of broadband decoupled 1 H NMR spectra that resemble an 1 H‐decoupled 13 C spectrum, with every proton resonance reduced to a singlet. Pure‐shift heteronuclear shift correlation methods are described next, followed by new long‐range heteronuclear chemical shift correlation experiments and then hyphenated techniques to identify components of complex, overlapped proton homonuclear spin systems. Techniques are also described for the unequivocal identification of vicinal neighbor carbon resonances that can be invaluable when dealing with complex impurities or degradation products. Covariance NMR data processing methods that allow 2D NMR experiments to be treated as large numerical matrices that can be manipulated using matrix algebraic operations are briefly discussed. Finally, anisotropic NMR methods are considered, which afford investigators the means of orthogonally verifying chemical structure constitution and configuration without investigator bias that often can lead to erroneously assigned structures. The latter eventuality, of course, can slow development timelines or could potentially have devastating patent protection consequences and regulatory implications.

show abstract

LR-HSQMBC versus LR-selHSQMBC: Enhancing the Observation of Tiny Long-Range Heteronuclear NMR Correlations

Cited by 7 publications

References 29 publications

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation

Advances in NMR‐Based Characterization of Drug Substances, Impurities, Degradants, and Drug Metabolites

Contact Info

Product

Resources

About