Utilizing unsymmetrical indirect covariance processing to define 15N13C connectivity networks

  title={Utilizing unsymmetrical indirect covariance processing to define 15N13C connectivity networks},
  author={Gary E. Martin and Patrick A. Irish and Bruce D. Hilton and Kirill A. Blinov and Antony J. Williams},
  journal={Magnetic Resonance in Chemistry},
There has been considerable interest over the past decade in the utilization of direct and long‐range 1H15N heteronuclear shift correlation methods at natural abundance to facilitate the elucidation of small molecule structures. Recently, there has also been a high level of interest in the exploration of indirect covariance NMR methods. Our initial explorations in this area led to the development of unsymmetrical indirect covariance methods, which allow the calculation of hyphenated 2D NMR… 

Unsymmetrical indirect covariance processing of hyphenated and long-range heteronuclear 2D NMR spect

Recent reports have demonstrated the unsymmetrical indirect covariance combination of discretely acquired 2D NMR experiments into spectra that provide an alternative means of accessing the

Application of unsymmetrical indirect covariance NMR methods to the computation of the 13C↔15N HSQC‐IMPEACH and 13C↔15N HMBC‐IMPEACH correlation spectra

Correlations for carbon resonances long‐range coupled to a protonated carbon in the 1H13C HMBC spectrum are transferred via the long-range 1H 15N coupling pathway in the1H15N IMPEACH spectrum to afford a much broader range of correlation possibilities in the 13C15N HMBC‐IMPEACH correlation spectrum.

Using indirect covariance spectra to identify artifact responses in unsymmetrical indirect covariance calculated spectra

Responses contained in indirect covariance processed HSQC spectra are reported as a means for the identification of artifacts in bothirect covariance and unsymmetrical indirect covariances processed 2D NMR spectra.

Multistep correlations via covariance processing of COSY/GCOSY spectra: opportunities and artifacts

Results obtained from covariance‐processed GCOSY spectra are fully analyzed and compared to normally processed COSY and 80 ms TOCSY spectra and the origin of artifact responses is analyzed.

Multidimensional Correlation Spectroscopy by Covariance NMR

An introduction is presented to covariance nuclear magnetic resonance (NMR) spectroscopy, which is a multidimensional method that characterizes physical spin correlations by their statistical

Covariance nuclear magnetic resonance methods for obtaining protein assignments and novel correlations.

  • A. KancherlaD. Frueh
  • Chemistry
    Concepts in magnetic resonance. Part A, Bridging education and research
  • 2017
Advances in covariance NMR are highlighted that permitted to generate reliable 4D arrays and how these arrays can be obtained from conventional NMR spectra are described.

(13)C-(15)N correlation via unsymmetrical indirect covariance NMR: application to vinblastine.

The elimination of artifact responses with aromatic solvent-induced shifts (ASIS) is shown in addition to a method of forecasting potential artifact responses through the indirect covariance processing of the GHSQC spectrum used in the unsymmetrical indirect covariances processing.

Posaconazole: Application of HSQC‐ADEQUATE from General Indirect Covariance Processing

The 1,1-ADEQUATE experiment provides unequivocal experimental access to adjacent carbon–carbon correlation information, albeit with a sensitivity penalty, as the experiment involves an adjacent 13C–13C out-and-back magnetization transfer.

Utilizing Long‐Range 1H–15N 2‐D NMR Spectroscopy for Chemical Structure Elucidation and Confirmation

15N can almost be considered a “forgotten” nuclide because of its low natural abundance, low γ, and the historical difficulty of direct observation NMR experiments. Indirect detection methods,

HSQC‐ADEQUATE: an investigation of data requirements

The results of an investigation of the reduction in acquisition time for the 1,1‐ADEQUATE data to take advantage of the s/n gain during the UIC processing to afford the final HSQC‐ADEquATE correlation plot are reported.



Analysis and elimination of artifacts in indirect covariance NMR spectra via unsymmetrical processing

Using an IDR (inverted direct response)‐HSQC‐TOCSY spectrum as a starting point for the indirect covariance processing, a spectrum that can be described as a carbon–carbon COSY experiment is obtained, and data are analogous to the autocorrelated 13C–13C double quantum INADEQUATE experiment except that the direct covariance NMR spectrum establishes carbon– carbon connectivities only between contiguous protonated carbons.

Long‐range carbon–carbon connectivity via unsymmetrical indirect covariance processing of HSQC and HMBC NMR data

Using experimentally discrete HSQC and HMBC data sets, it is shown that unsymmetrical indirect covariance processing of the pair of NMR spectra affords a presentation containing long‐range carbon–carbon connectivity information.

Unsymmetrical covariance processing of COSY or TOCSY and HSQC NMR data to obtain the equivalent of HSQC‐COSY or HSQC‐TOCSY spectra

Artifacts observed in the indirect covariance NMR spectrum of HSQC-TOCSY data have recently been analyzed and a method for their elimination proposed. More recently, unsymmetrical covariance

The use of unsymmetrical indirect covariance NMR methods to obtain the equivalent of HSQC‐NOESY data

The application of the unsymmetrical indirect covariance NMR methods to the combination of HSQC and NOESY spectra is demonstrated to provide results comparable toHSQC‐NOESY data, albeit with greater sensitivity and with considerably less spectrometer time.

15N NMR Spectroscopy in Structural Analysis

The implementation of both the directly and the inversely detected 15N NMR techniques at the natural abundance level of the 15N isotope is demonstrated for a diverse array of structural problems in

Covariance nuclear magnetic resonance spectroscopy.

Covariance nuclear magnetic resonance (NMR) spectroscopy is introduced, which is a new scheme for establishing nuclear spin correlations from NMR experiments that neither involves a second Fourier transformation nor does it require separate phase correction or apodization along the indirect dimension.

Theory of covariance nuclear magnetic resonance spectroscopy.

It is shown that for a large class of 2D NMR experiments the covariance spectrum and the 2D Fourier transform spectrum can be related to each other by means of Parseval's theorem.

Application of accordion excitation in 1H– 15N long‐range heteronuclear shift correlation experiments at natural abundance

Accordion excitation provides the means of sampling a broad range of potential long‐range heteronuclear couplings in a single experiment. Two long‐range heteronuclear experiments, ACCORD‐HMBC and

Indirect covariance NMR spectroscopy.

A novel NMR scheme is presented that establishes homonuclear spin correlations without requiring direct detection of the spin species, which opens up new avenues for the experimental analysis of molecules containing insensitive spins encountered in biomolecular NMR and analytical chemistry including metabolomics.