Simplified multiplet pattern HSQC-TOCSY experiment for accurate determination of long-range heteronuclear coupling constants

A new two-dimensional pulse sequence for accurately determining heteronuclear coupling constants is presented. It is derived from HSQC and HECADE techniques with B0 gradient coherence selection. The main feature of the proposed method is spectra with only one component of the IS doublet; i.e., the final result is equivalent to a selective broadband excitation of either Salpha or Sbeta spin states and a preservation of these states during the entire experiment. The effect is obtained by an appropriate combination of in- and antiphase coherences. It is demonstrated that heteronuclear single-bond as well as long-range coupling constants and their relative signs are readily evaluated. The proposed sequence is equally or less sensitive to a variation of heteronuclear one-bond couplings than previously published, closely related sequences. The new method is applied to a peptide sample for determination of 3JN, Hbeta.     

Accurate measurement of long-range heteronuclear coupling constants from undistorted multiplets of an enhanced CPMG-HSQMBC experiment

Here, we present a modified CPMG-HSQMBC experiment which is capable to reduce the detrimental phase twists in the "long-range" connectivity multiplets caused by proton-proton couplings. We demonstrate that concerted CPMG pulse trains applied on both nuclei in the starting CPMG-INEPT transfer step can considerably be improved by composite pi pulses that compensate for pulse imperfections and off-resonance effects. Experimental optimization of the interpulse delay within the CPMG cycle was found to be crucial in order to achieve the best possible "decoupling" of homonuclear coupling modulation.     

Accurate measurements of multiple-bond 13C-1H coupling constants from phase-sensitive 2D INEPT spectra.

Measurements of multiple-bond 13C-)H coupling constants are of great interest for the assignment of nonprotonated 13C resonances and the elucidation of molecular conformation in solution. Usually, the heteronuclear multiple-bond coupling constants were measured either by the J(CH) splittings mostly in selective 2D spectra or in 3D spectra, which are time consuming, or by the cross peak intensity analysis in 2D quantitative heteronuclear J correlation spectra (1994, G. Zhu, A. Renwick, and A. Bax, J. Magn. Reson. A 110, 257; 1994, A. Bax, G. W. Vuister, S. Grzesiek, F. Delaglio, A. C. Wang, R. Tschudin, and G. Zhu, Methods Enzymol. 239, 79.), which suffer from the accuracy problem caused by the signal-to-noise ratio and the nonpure absorptive peak patterns. Concerted incrementation of the duration for developing proton antiphase magnetization with respect to carbon-13 and the evolution time for proton chemical shift in different steps in a modified INEPT pulse sequence provides a new method for accurate measurements of heteronuclear multiple-bond coupling constants in a single 2D experiment.     

Sensitivity enhancement of a two-dimensional experiment for the measurement of heteronuclear long-range coupling constants, by a new scheme of coherence selection by gradients

In this work we present a new pulse sequence for the measurement of long-range heteronuclear coupling constants in which the optimization of coherence selection by pulsed field gradients offers a net increase in sensitivity. This type of experiments is extremely valuable for conformational studies of molecules in natural abundance and in this context the use of gradients is essential for an efficient suppression of (12)C bound proton signals. A comparative analysis of the different gradient schemes available is presented with a conclusive elucidation of the relative sensitivities. Our gradient scheme could be advantageous as a building block for other related experiments.     

PFG-omega1-filtered TOCSY experiments for the determination of long-range heteronuclear and homonuclear coupling constants and estimation of J-coupling "crosstalk" artifacts in 2-D omega1-filtered "E. COSY-style" spectra.

We present novel one- and two-dimensional versions of the omega1-filtered TOCSY experiment. These experiments utilize pulsed-field gradient techniques and INEPT-reverse INEPT magnetization transfer to generate heteronuclear filtering by means of coherence pathway selection. The major advantages of this approach are twofold: first, each experiment requires a reasonable number of transmitter pulses, gradient pulses, and delays to implement. Second, the use of z-axis gradients at the beginning and termination of the pulse sequences prevents the recovery of dephased magnetization prior to FID detection. This technique was incorporated into 1-D and 2-D omega1-filtered JXH- and JHH-TOCSY-style experiments. As demonstrated on 15N-enriched peptide samples, the use of the pulsed-field-gradient coherence selection scheme effectively filters out unwanted magnetization components, thereby improving the overall sensitivity of the experiments. In addition to this suite of pulse sequences, we also present a method for correcting the reduction in J-coupling that results from crosspeak shifting in 2-D omega1-filtered E. COSY-style spectra. This correction is applicable to both Lorentzian and Gaussian 2-D crosspeak lineshapes.     

Nuclear spin-spin coupling constants prediction based on XGBoost and LightGBM algorithms

Nuclear magnetic resonance (NMR) is a robust method for the analysis of molecular complex structures, and the measurement of the nuclear spin–spin coupling constant is the key. In this paper, based on the 3D coordinates of the atoms in the molecule, the spin–spin coupling constants of atom-pairs are directly predicted using Extreme Gradient Boosting (XGBoost) and Light Gradient Boosting Machine (LightGBM). The calculated result of DFT method is taken as the target value. Experiment shows that LightGBM (R²: 0.93) overall performance is better than XGBoost. In some molecules, the predicted fit (R²) of the coupling constant between atoms even reached 1.00. This research avoids complex quantum mechanics and can assist in NMR to gain insight into the structure and dynamics of molecules, thereby enriching the data information analysis method of nuclear magnetic interaction.     

(1)H-Detected IPAP DEPT-INADEQUATE and IPAP RINEPT-INADEQUATE for the measurement of long-range carbon-carbon coupling constants

The sensitivity of cryoprobes, which are rapidly becoming available, have brought about the possibility of measurement of (13)C, (13)C coupling constants at the natural abundance of (13)C using tens rather than hundreds of milligrams of compounds. This relatively recent development lays the foundation for a more routine use of the (13)C, (13)C long-range coupling constants in the conformational analysis of molecules. We have designed novel (1)H-detected INADEQUATE experiments optimized for long-range (13)C, (13)C correlations and the measurement of long-range coupling constants. These experiments incorporate refocusing of (1)J(CH) coupling constants prior to the formation of DQ coherences and (1)H-decoupling during the long carbon-carbon evolution intervals. Such modifications significantly enhance their performance over (1)H-detected INADEQUATE experiments currently in use for mapping the one-bond (13)C, (13)C correlations. (1)H or (13)C polarization is used a starting point in long-range correlation (1)H-detected IPAP DEPT-INADEQUATE or RINEPT-INADEQUATE experiments. These correlation experiments were modified yielding in-phase (IP) or antiphase (AP) (13)C, (13)C doublets in F(1). Procedures were developed for their editing yielding accurate values of small (13)C, (13)C coupling constants. The methods are illustrated using mono- and disaccharide samples and compared with related (13)C-detected experiments by means of the measurement of interglycosidic (13)C, (13)C coupling constants of a disaccharide.     

Spin-edited 2D HSQC-TOCSY experiments for the measurement of homonuclear and heteronuclear coupling constants: application to carbohydrates and peptides

Simple modifications of the sensitivity-improved HSQC-TOCSY pulse sequence are proposed for the easy determination of the sign and the magnitude of homonuclear and heteronuclear coupling constants. Whereas in well-resolved regions, a clean two-component E.COSY-like pattern allows a direct measurement from a single 2D spectrum, separate acquisition of equivalent single-component TROSY/anti-TROSY spectra becomes highly interesting when spectral crowding complicates the spectral analysis. It is also demonstrated that an additional restricted planar mixing element after the isotropic TOCSY process completely retains all spin-editing features and permits the accurate measurement of the sign and the size of the corresponding homonuclear proton-proton coupling constants. Among others, the proposed techniques are particularly suited for molecules presenting a great number of CH and NH spin systems. Examples and practical details of the implementation of these techniques on standard carbohydrates and peptides at 13C and 15N natural abundance are provided.     

Determination and application of values of inter-ring F,F coupling constants

The relative signs and magnitudes of long-range inter-ring coupling constants have been determined in the compounds 2-methoxypentafluoro-, 5-chloropentafluoro-, and hexafluoroquinoxaline; 1-methoxypentafluoro- and hexafluorophthalazine; 2,4-dimethoxypentafluoroquinoline, and N-methoxyethyl-4-methoxypentafluoroquinolone. Inter-ring F,F coupling constants, excluding J_F,F^peri alternate in sign and magnitude. One important long-range effect is the enhancement of 6,8, meta F,F coupling by a 2-position ring nitrogen. A large ortho F,F coupling of 29.7 Hz is reported and a peri N-methyl (H)-fluorine coupling of 9.82 Hz is noted.     

Selective suppression and excitation of solid-state NMR resonances based on quadrupole coupling constants

The dependence of the (Rotor Assisted Population Transfer) RAPT enhancement on offset frequency for nuclei experiencing different quadrupolar couplings has been exploited to design two new spectral editing schemes, pi/2-RAPT and RAPT-pi-RAPT, for the selective excitation or suppression, respectively, of nuclei with large quadrupolar couplings. Both approaches are demonstrated on the 87 Rb spectrum of Rb(2)SO(4), which contains two resonances with C(q) values of 2.6 and 5.3 MHz. The conditions for optimal selectivity are discussed. Combining pi/2-RAPT with the RIACT MQ-MAS experiment it is also demonstrated how a pure absorption mode triple quantum MQ-MAS spectrum devoid of narrow resonances can be obtained.     

Development of a method for the measurement of long-range 13C-1H coupling constants from HMBC spectra

This paper describes a number of improvements to a method, developed in this laboratory and described in J. Magn. Reson. 85 (1989) 111-113, which makes it possible to determine values of long-range 13C-1H coupling constants from heteronuclear multiple bond correlation (HMBC) spectra. First, it is shown how pulsed-field gradients can be introduced into the HMBC experiment without perturbing the form of the cross-peak multiplets; a one-dimensional version of the experiment is also described which permits the rapid measurement of a small number of couplings. Second, the experiment is modified so that one-bond and long-range cross-peaks can be separated, and so that the one-bond cross-peaks have more reliable intensities. Finally, it is shown how these one-bond cross-peaks can be used to advantage in the fitting procedure.     

Renormdynamics of coupling constants and masses

Renormdynamics of couplings constants and masses considered.     

1H-detected double-J-modulated INEPT-INADEQUATE for simultaneous determination of one-bond and long-range carbon-carbon connectivities and the measurement of all carbon-carbon coupling constants

We describe a new NMR experiment, (1)H-detected double-J-modulated (DJM)-INEPT-INADEQUATE, for tracing out the carbon skeleton of molecules. This experiment allows simultaneous correlation of directly bonded carbon atoms and those separated by multiple bonds, while at the same time also providing the values of all J(CC) coupling constants. This is achieved by replacing both fixed carbon-carbon coupling evolution intervals of the INEPT-INADEQUATE experiment by variable time intervals, which are incremented in concert with the DQ evolution period (t(1)). We show that the analysis of the fine structure of cross-peaks in DJM-INEPT-INADEQUATE spectra leads to accurate values of coupling constants and give guidelines for the proper usage of the method. The proposed experiment is two times less sensitive that the original INEPT-INADEQUATE experiment. We show that, using a 600-MHz cryoprobe and 20 mg of a monosaccharide, spectra that are suitable for the analysis of coupling constants as small as 2 Hz can be obtained within 24 h. Instead of performing multiple experiments, a single DJM-INEPT-INADEQUATE experiment can thus provide a wealth of information for the structural analysis of small molecules.     

Determination of the relative signs of proton spin coupling constants by double irradiation

The method of Evans [1] for determining relative signs of nuclear spin coupling constants by double irradiation experiments has been extended to the case where the three coupled nuclei are all protons. It is thus possible to demonstrate from the high resolution proton magnetic resonance spectrum of the ring protons of 2-Furoic acid that the three spin coupling constants are all of like sign.     

Determination of the relative signs of proton spin coupling constants by double irradiation

The method of Evans [1] for determining relative signs of nuclear spin coupling constants by double irradiation experiments has been extended to the case where the three coupled nuclei are all protons. It is thus possible to demonstrate from the high resolution proton magnetic resonance spectrum of the ring protons of 2-Furoic acid that the three spin coupling constants are all of like sign.     

Influence of coupling constants on nuclear symmetry energy

By studying the energy of neutron star matter, we discuss the nuclear symmetry energy at different baryon densities and different coupling constants in the relativistic mean field approximation. The results show that the symmetry energy increases with baryon density at various coupling constants and incompressibilities. Further-more, the symmetry energy at saturation density increases with increasing incompressibility at fixed d, and decreases at fixed c. Specifically, when coupling constants gv and gs are fixed, respectively, the symmetry energy has a little change with increasing incompressibility. It is demonstrated that the NN coupling constants have greater influences on the symmetry energy than the self-coupling constants.     

Hyperfine coupling constants and their dependence on charge densities

In paramagnetic aromatic systems the relation between the hyperfine coupling constants a _H for the protons and the spin density ρ on the adjacent carbon atom is usually given by the relation a _H = -Qρ (McConnell) in which Q is a constant characteristic for the C-H bond. In the paramagnetic ions of aromatic molecules the carbon atoms have in general besides a non-zero spin density also a non-zero excess charge density.

If one takes into account both the effect of the spin density ρ and the excess charge density ε on the C-H bond, the following formula is obtained for the proton hyperfine coupling constant:

in which Q and K are predicted to be positive constants of the same order of magnitude.

Comparison with experimental data gives Q = 31·2 gauss; K = 17 gauss.     

Compilation of coupling constants and low-energy parameters

The electron capture decay ${}^{163}\text{Ho}\text{→}{}^{163}\text{Dy}{}^{\mathrm{<mtext>H</mtext>}}\text{+ν}{}_{\mathrm{<mtext>e</mtext>}}$ occurs with a record low energy release, Q ～ 2.6 keV. The daughter Dy^H atom has an electron hole, H, and predominantly decays by electron ejection Dy^H→Dy^H₁H₂+e^?. We investigate the neutrino mass sensitivity of the electron spectrum in the overall process Ho→Dy^H₁H₂+e^?+ν_e. In this spectrum, the fraction of events sensitive to a fixed non-zero neutrino mass in one to two orders of magnitude smaller than in the standard case of tritium β decay. But the electron energies in ¹⁶³Ho decay are considerably smaller than in ³H decay (Q ～ 18 keV). This suggests experiments whose energy resolution could be much better than that of the magnetic spectrometers conventionally used in the tritium case.