Off-resonance Decoupling Research Articles

Reaction monitoring using hyperpolarized NMR with scaling of heteronuclear couplings by optimal tracking

Off-resonance decoupling using the method of Scaling of Heteronuclear Couplings by Optimal Tracking (SHOT) enables determination of heteronuclear correlations of chemical shifts in single scan NMR spectra. Through modulation of J-coupling evolution by shaped radio frequency pulses, off resonance decoupling using SHOT pulses causes a user-defined dependence of the observed J-splitting, such as the splitting of 13C peaks, on the chemical shift offset of coupled nuclei, such as 1H. Because a decoupling experiment requires only a single scan, this method is suitable for characterizing on-going chemical reactions using hyperpolarization by dissolution dynamic nuclear polarization (D-DNP). We demonstrate the calculation of [13C, 1H] chemical shift correlations of the carbanionic active sites from hyperpolarized styrene polymerized using sodium naphthalene as an initiator. While off resonance decoupling by SHOT pulses does not enhance the resolution in the same way as a 2D NMR spectrum would, the ability to obtain the correlations in single scans makes this method ideal for determination of chemical shifts in on-going reactions on the second time scale. In addition, we present a novel SHOT pulse that allows to scale J-splittings 50% larger than the respective J-coupling constant. This feature can be used to enhance the resolution of the indirectly detected chemical shift and reduce peak overlap, as demonstrated in a model reaction between p-anisaldehyde and isobutylamine. For both pulses, the accuracy is evaluated under changing signal-to-noise ratios (SNR) of the peaks from reactants and reaction products, with an overall standard deviation of chemical shift differences compared to reference spectra of 0.02ppm when measured on a 400MHz NMR spectrometer. Notably, the appearance of decoupling side-bands, which scale with peak intensity, appears to be of secondary importance.

Measurement of J-couplings between chemically equivalent nuclei using off-resonance decoupling

The method of measuring J-couplings between chemically equivalent nuclei in isotopically/magnetically non-equivalent environment, based on off-resonance decoupling, is described. The approach uses intensities, rather than frequencies of the spectral peaks and, therefore, the accuracy of measurement is not limited by spectral resolution.

Multidimensional J-driven NMR correlations by single-scan offset-encoded recoupling

Two-dimensional (2D) correlations between bonded heteroatoms, lie at the cornerstone of many uses given to contemporary nuclear magnetic resonance (NMR). Improving the efficiency with which these correlations are established is an important topic in modern NMR, with potential applications in rapid chemical analysis and dynamic biophysical studies. Alternatives have been developed over the last decade to speed up these experiments, based among others on reducing the number of data points that need to be sampled, and/or shortening the inter-scan delays. Approaches have also been proposed to forfeit multi-scan schemes altogether, and complete full 2D correlations in a single shot. Here we explore and discuss a new alternative enabling the collection of such very fast – in principle, single-scan – acquisitions of 2D heteronuclear correlations among bonded species, which operates on the basis of a partial reintroduction of J couplings. Similar approaches had been proposed in the past based on collecting coupled spectra for arrays of off-resonance decoupling values; the proposal that is here introduced operates on the basis of suitably incorporating frequency-swept pulses, into spin-echo sequences. Thanks to the offset-dependent amplitude modulations of the in- and anti-phase components that such sequences impart, chemical shifts of coupled but otherwise unobserved nuclear species, can be extracted from the relative intensities and phases of J-coupled multiplets observed in one-dimensional acquisitions. A description of the steps needed to implement this rapid acquisition approach in a quantitative fashion, as well as applications of the ensuing sequences, are presented.

Tailored real-time scaling of heteronuclear couplings

Heteronuclear couplings are a valuable source of molecular information, which is measured from the multiplet splittings of an NMR spectrum. Radiofrequency irradiation on one coupled nuclear spin allows to modify the effective coupling constant, scaling down the multiplet splittings in the spectrum observed at the resonance frequency of the other nuclear spin. Such decoupling sequences are often used to collapse a multiplet into a singlet and can therefore simplify NMR spectra significantly. Continuous-wave (cw) decoupling has an intrinsic non-linear offset dependence of the scaling of the effective J-coupling constant. Using optimal control pulse optimization, we show that virtually arbitrary off-resonance scaling of the J-coupling constant can be achieved. The new class of tailored decoupling pulses is named SHOT (Scaling of Heteronuclear couplings by Optimal Tracking). Complementing cw irradiation, SHOT pulses offer an alternative approach of encoding chemical shift information indirectly through off-resonance decoupling, which however makes it possible for the first time to achieve linear J scaling as a function of offset frequency. For a simple mixture of eight aromatic compounds, it is demonstrated experimentally that a 1D-SHOT {1H}–13C experiment yields comparable information to a 2D-HSQC and can give full assignment of all coupled spins.

Thermal Isomerization of Cohumulone

Thermal isomerization is a key step in converting α-acids into iso-α-acids during the kettle boiling process. In an effort to understand the nature of this reaction in order to produce iso-α-acids more efficiently, we studied the thermal isomerization reaction of α-acids under more closely controlled conditions in the absence of acids, bases, metal catalysts, oxygen, and light. Cohumulone was synthesized as the starting compound and thermally isomerized in nonaqueous solutions under a dark, nitrogen environment. We found that mainly cis-isocohumulone was very inefficiently produced, which might be followed by a nonconcerted reaction. The stereochemical assignment of cis- and trans-isocohumulones was reinvestigated using 13C NMR techniques, including the nuclear Overhauser effect, off-resonance decoupling, and integration using chromium acetylacetonate.

Chemical Shift Correlations from Hyperpolarized NMR by Off-Resonance Decoupling

Nuclear magnetic resonance, through observation of chemical shift, allows the separate identification of each atom in a molecule. Thus, NMR spectra impart an often unrivaled wealth of information on molecular structure. A particular advantage of NMR spectroscopy is the ability to record multidimensional spectra, which provide correlations between atoms. When compared to other techniques, such as optical spectroscopy, the acquisition of NMR spectra is however an insensitive process, requiring samples of high concentration and long acquisition times. Recently, it has been demonstrated that dynamic nuclear polarization, a hyperpolarization technique, can increase the NMR signal by several orders of magnitude. Here, we present a robust method that allows recording two-dimensional chemical shift correlations from such hyperpolarized molecules. The method makes use of an apparent scaling of the scalar coupling observed on one type of atom, when an off-resonance decoupling field is applied to another type of atom. Thus, two-dimensional chemical shift correlations can be read directly from a small number of scans acquired using a hyperpolarized sample. Due to the ease of implementing this technique on commercial hyperpolarization and NMR equipment, it appears ideally suited for routine application, for example, to obtain carbon-proton chemical shift correlations in organic molecules.

Fast multidimensional NMR spectroscopy by spin-state selective off-resonance decoupling (SITAR)

Spin-state selective off-resonance decoupling (SITAR) is applied to the amide proton-to-nitrogen-to-alpha-carbon correlation (HNCA) triple-resonance experiment by measuring the 15N chemical shift during the acquisition simultaneously with the 1H chemical shift. The simultaneous detection of both 1H and 15N chemical shifts in SITAR reduces the dimensionality of the HNCA-type experiment from three dimensions to two dimensions with a 15N chemical shift resolution of approximately 0.4 ppm. This enables the recording of triple-resonance experiments in several minutes. SITAR is furthermore applied to the amide proton-to-nitrogen-to-alpha-carbon-and-beta-carbon correlation (HNCACB) triple-resonance experiment and the 15N-resolved [1H,1H]-nuclear Overhauser enhancement spectroscopy (NOESY) experiment with similar success. The accompanied peak crowding and chemical shift degeneracy of the amide protons in the SITAR two-dimensional (2D) spectra, which are inherent properties of pseudo-dimensional experiments, are resolved by local correlation of the two sub-spectra. With this procedure a 13C--1H strip for each 15N--1H moiety is generated resulting in a three-dimensional (3D) strip list known from the conventional 3D spectra. The quality of the strip list in terms of peak crowding and chemical shift degeneracy is comparable to their corresponding 3D counterparts. An analysis-software within the CARA package is presented, which generates, visualizes and manages the SITAR spectra, the corresponding strip lists and the assignment process.

Suppression of artifacts induced by homonuclear decoupling in amino-acid-type edited methyl 1H– 13C correlation experiments

A detailed theoretical and experimental analysis of the artifacts induced by homonuclear band-selective decoupling during CT frequency labeling is presented. The effects are discussed in the context of an amino-acid-type editing filter implemented in 1H– 13C CT-HSQC experiments of methyl groups in proteins. It is shown that both Bloch–Siegert shifts and modulation sidebands are efficiently suppressed by using additional off-resonance decoupling as proposed by Zhang and Gorenstein [J. Magn. Reson. 132 (1998) 81], and appropriate adjustment of a set of pulse sequence parameters. The theoretical predictions are confirmed by experiments performed on 13C-labeled protein samples, yielding artifact-free amino-acid-type edited methyl spectra.

Pseudomultidimensional NMR by spin-state selective off-resonance decoupling.

An alternate technique for accurately monitoring the chemical shift in multidimensional NMR experiments using spin-state selective off-resonance decoupling is presented here. By applying off-resonance decoupling on spin S during acquisition of spin I, we scaled the scalar coupling J(I,S) between the spins, and the residual scalar coupling turns out to be a function of the chemical shift of spin S. Thus, the chemical shift information of spin S is indirectly retained, without an additional evolution period and the accompanying polarization transfer elements. The detection of the components of the doublet using spin-state selection enables an accurate measurement of the residual scalar coupling and a precise value for the chemical shift, concomitantly. The spin-state selection further yields two subspectra comprising either one of the two components of the doublet and thereby avoiding the overlap problems that arise from off-resonance decoupling. In general, spin-state selective off-resonance decoupling can be incorporated into any pulse sequence. Here, the concept of spin-state selective off-resonance decoupling is applied to 3D (13)C or (15)N-resolved [(1)H,(1)H]-NOESY experiments, adding the chemical shift of the heavy atom attached to the hydrogen ((13)C or (15)N nuclei) with high resolution resulting in a pseudo-4D. These pseudo-4D heavy-atom resolved [(1)H, (1)H]-NOESY experiments contain chemical shift information comparable to that of 4D (13)C or (15)N-resolved [(1)H,(1)H]-NOESY, but with an increase in chemical shift resolution by 1-2 orders of magnitude.

Systematic design and evaluation of multiple-pulse experiments in nuclear magnetic resonance spectroscopy using a semi-continuous Baker–Campbell–Hausdorff expansion

We show that an explicit solution to a semi-continuous analog to the Baker–Campbell–Hausdorff (BCH) problem can be derived by an appropriate combination of the Magnus and BCH expansions. The resulting semi-continuous BCH (scBCH) expansion forms a valuable tool for solving the time-dependent Schrödinger equation for Hamiltonians with complicated, piecewise continuous time dependence. Such Hamiltonians are typical in multiple-pulse coherent spectroscopy. Using the scBCH expansion we derive a number of general formulas, including relations for permuted pulse sequences. These formulas simplify calculation of the effective Hamiltonian for advanced multiple-pulse experiments and allow for evaluation of this to considerably higher order than is possible using the Magnus expansion. This is important for the detailed analysis and systematic design of multiple-pulse experiments which emphasize some interactions while effectively suppressing others. The scBCH expansion is applied to problems of homonuclear dipolar decoupling in solid-state NMR and broadband heteronuclear decoupling in liquid-state NMR. Improved high-order pulse sequences for on- and off-resonance decoupling are introduced and existing recursive expansion strategies are evaluated within the presented theoretical framework.

False AA'X Spin-Spin Coupling Systems in 13C NMR: Examples Involving Phosphorus and a 20-Year-Old Mystery in Off-Resonance Decoupling

It is common in both NMR textbooks and journal articles to loosely describe certain ABX spin systems, in which the nuclei in the AB pair are rendered chemically inequivalent by proximity of one to 12C and the other to 13C, as AA'X spin systems. While the chemical shifts normally are indistinguishable and so for all practical purposes such systems can be analyzed as AA'X, there is a danger that when the chemical shifts are not the same, one may fail to recognize that fact due to the assumption that the isotopomer shift is always insignificant. Examples of such false AA'X spectra are described for diphosphorus organic and organometallic compounds, in which DeltavPP' = 2.5 - 4 Hz using a 400 MHz (1H) NMR spectrometer; at lower field strength the ABX splitting might be expected to disappear due to the reduction in DeltavPP'. An example involving 13C off-resonance decoupling in the NMR spectra of maleic anhydride was shown to depend on decoupler power: at low power, the system is ABX, while at the high power n...

New Multinuclear Experiments on Solid Organotin Fluorides

nBu3SnF and Mes3SnF (Mes = mesityl) are organotin fluorides that have direct Sn–F bonds. The119Sn and19F NMR spectra of these compounds have been measured using a selection of CPMAS probes. Doubly decoupled {1H,19F} as well as singly decoupled {1H}119Sn NMR spectra are shown. Double decoupling gives higher resolution spectra and allows the sample of Mes3SnF to be spun slower to give more spinning-sidebands without overlapping of signals, giving improved analysis. The doubly decoupled spectra are sensitive to the power and offset of the decouplers. The effect of off-resonance decoupling has been observed for119Sn NMR through reduced splittings when the19F decoupler power and offset were varied. Proton-decoupled19F spectra have been measured using a new HF double-resonance probe. In addition, two-dimensional heteronuclear correlation spectra are presented for Mes3SnF, allowing a full assignment for the19F and119Sn chemical shifts of the two sites. Full shielding tensor data are reported for both compounds. Values have been derived for the effective (119Sn,19F) dipolar coupling constants from both119Sn and19F experiments, yielding estimates of coupling anisotropy.

Effect of Proton Spin Exchange on the Residual 13C MAS NMR Linewidths. Phase-Modulated Irradiation for Efficient Heteronuclear Decoupling in Rapidly Rotating Solids

An increase of the 13C NMR linewidth with increasing rate of magic-angle spinning observed for certain solids under high-power proton decoupling is shown to be a consequence of the slowing of proton spin exchange at high spinning speeds. This accentuates the effects of off-resonance decoupling and leads to an inhomogeneous broadening of the 13C lines. It is demonstrated that periodic phase-modulated irradiation is able to restore the condition of on-resonance decoupling and to maintain the spectral resolution observed at moderate spinning speeds, where spin exchange is more efficient.

Unusual Hindered Rotation of an Unsubstituted Phenyl Group. Variable Temperature1H NMR Studies and Preliminary13C Assignments in Ketazolam

Abstract An unusual hindered rotation of an unsubstituted phenyl group in the drug, ketazolam, has been found at ambient temperature. Variable temperature lH NMR has been employed to examine the two- fold rotation about the C(sp2)-C(sp3) bond. Chemical shift as- signments of the IH NMR spectra and partial assignments of the 13C spectra are supported by off-resonance decoupling, gated decou- pling, and low temperature 2D l3C-1H heteronuclear chemical shift correlation experiments at 200.1 MHz for IH and 50.3 MHz for 13C.

Pseudo-four-dimensional NMR by off-resonance decoupling: an approach for distinguishing coupled proton pairs by the frequencies of their attached heteronuclei

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPseudo-four-dimensional NMR by off-resonance decoupling: an approach for distinguishing coupled proton pairs by the frequencies of their attached heteronucleiStephen W. Fesik, Hugh L. Eaton, Edward T. Olejniczak, and Robert T. Gampe Jr.Cite this: J. Am. Chem. Soc. 1990, 112, 13, 5370–5371Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://doi.org/10.1021/ja00169a066RIGHTS & PERMISSIONSArticle Views57Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (329 KB) Get e-Alerts Get e-Alerts

13C NMR imaging of solids with magic angle sample spinning

The first 13C NMR imaging method suitable for rotating solids is demonstrated and is shown to allow high-resolution ( approximately=100 mu m) accurate images to be obtained. Line narrowing is achieved by a combination of magic angle sample spinning (MAS), high-power proton decoupling and deconvolution. The small homogeneous linewidth, high-Q probes and narrow-band receivers associated with 13C NMR compensate to a large extent for the low natural abundance and small gyromagnetic ratio of 13C. The resolution and sensitivity of 13C imaging, which is generally simpler to perform, are comparable to those of multiple pulse 1H imaging. Limitations of the method due to the residual broadening from off-resonance proton decoupling and interference of the MAS averaging of the chemical shift anisotropy by modulated magnetic field gradients are discussed.

Biosynthetic studies on validamycins. I. 1H and 13C NMR assignments of validamycin A.

The 1H and 13C NMR spectra of validamycin A have been assigned by use of 2D homonuclear correlation spectroscopy for protons, and off-resonance decoupling, single frequency off-resonance decoupling, and comparison studies with model compounds for carbons. Effects of pH on carbon chemical shifts have also been studied.

Carbon13 NMR of Z- and E-Doxepin Hydrochloride

Carbon13 chemical shift assignments are reported for Z- and E-doxepin hydrochloride [ Z- and E-N,N,-dimethyl-dibenz[b,e]oxepin-delta-11(6H)], gamma-propylamine hydrochloride, and related model compounds. Doxepin hydrochloride, a mixture of approximately 85% E- and 15% Z-isomer is of clinical importance as an antidepressant drug. Previous proton NMR studies indicated that the dibenz(b,e,)oxepin ring exists in two conformations. This study indicates that one conformation may be favored for each isomer with alkylamino olefinic substituent orientation above the most adjacent aromatic ring. Homoand heteronuclear shift-correlated 2D NMR, selective INEPT, selective and off-resonance decoupling, and inversion-recovery ( T1) experiments as well as model compound comparisons were used in assignments.

Carbon13 NMR Shift Assignments for E- and Z-Dothiepin Hydrochloride and 6H-Dibenzo[b,e]thiepin-11-One

Carbon13 chemical shift assignments are reported for Z- and E-dothiepin hydrochloride (N,N-dimethyldibenzo[b,e]thiepin- delta-11(6H)′, gamma-propylamine hydrochloride). The commercial product, a mixture of approximately 95% E-isomer, is of clinical importance as an antidepressant drug. The precursor and degradation product, 6H-dibenzo[b,e]thiepin-11-one, and related model compounds were also studied. Homo- and heteronuclear shift-correlated 2D NMR, selective INEPT, selective and off-resonance decoupling, and inversion-recovery ( T1) experiments as well as model compound comparisons were used in assignments.

Ｐｉｅｒｉｓｔｏｘｉｎ類およびＡｓｅｂｏｔｏｘｉｎＩＶの炭素‐１３核磁気共鳴スペクトルについて

The 13C-NMR spectra of pieristoxin C, G, H, J and K, and asebotoxin IV of leaves of Pieris japonica D. Don were clarified by single-frequency off-resonance decoupling, selective proton decoupling and partially relaxed Fourier transformation experiment. The spectra were then compared with those of grayanotoxin III, rhodojaponin III and their analogs.