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.     

Low-power composite CPMG HSQMBC experiment for accurate measurement of long-range heteronuclear coupling constants

A modified version of CPMG-HSQMBC pulse scheme is presented for the measurement of long-range heteronuclear coupling constants. The method implements adiabatic inversion and refocusing pulses on the heteronucleus. Low-power composite 180° XY-16 CPMG pulse train is applied on both proton and X nuclei during the evolution of long-range couplings to eliminate phase distortions due to co-evolution of homonuclear proton-proton couplings. The pulse sequence yields pure absorption antiphase multiplets allowing precise and direct measurement of the (n)J(XH) coupling constants regardless from the size of the proton-proton couplings. The applicability of the method is demonstrated using strychnine as a model compound. The selective 1D version of the method is also presented.     

Long-range J(CH) heteronuclear coupling constants in cyclopentane derivatives

Detailed measurements of long-range heteronuclear spin-spin coupling constants, especially (2, 3)J(CH) spin-spin couplings for various cyclopentane derivatives, are reported. The measurements are based on a 2D heteronuclear correlation experiment named G-BIRD(R, X)-CPMG-HSQMBC.     

Precise Measurement of Long‐Range Heteronuclear Coupling Constants by a Novel Broadband Proton–Proton‐Decoupled CPMG‐HSQMBC Method

A broadband proton–proton‐decoupled CPMG‐HSQMBC method for the precise and direct measurement of long‐range heteronuclear coupling constants is presented. The Zangger–Sterk‐based homodecoupling scheme reported herein efficiently removes unwanted proton–proton splittings from the heteronuclear multiplets, so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between singlet maxima in the resulting spectra. The proposed pseudo‐1D/2D pulse sequences were tested on nucleotides, a metal complex incorporating P heterocycles, and diglycosyl (di)selenides, as well as on other carbohydrate derivatives, for the extraction of ⁿJ(¹H,³¹P), ⁿJ(¹H,⁷⁷Se), and ⁿJ(¹H,¹³C) values, respectively.     

PSYCHE CPMG–HSQMBC: An NMR Spectroscopic Method for Precise and Simple Measurement of Long‐Range Heteronuclear Coupling Constants

Among the NMR spectroscopic parameters, long‐range heteronuclear coupling constants convey invaluable information on torsion angles relevant to glycosidic linkages of carbohydrates. A broadband homonuclear decoupled PSYCHE CPMG–HSQMBC method for the precise and direct measurement of multiple‐bond heteronuclear couplings is presented. The PSYCHE scheme built into the pulse sequence efficiently eliminates unwanted proton–proton splittings from the heteronuclear multiplets so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between peak maxima of pure antiphase doublets. Moreover, PSYCHE CPMG–HSQMBC can provide significant improvement in sensitivity as compared to an earlier Zangger–Sterk‐based method. Applications of the proposed pulse sequence are demonstrated for the extraction of ⁿJ(¹H,⁷⁷Se) and ⁿJ(¹H,¹³C) values, respectively, in carbohydrates; further extensions can be envisioned in any J‐based structural and conformational studies.     

1-Cyclohepta-2,4,6-trienyl-selanes--a 77Se NMR study: indirect nuclear 77Se--13C spin-spin coupling constants and application of density functional theory (DFT) calculations

1-Cyclohepta-2,4,6-trienyl-selanes Se(C(7)H(7))(2) (2c), R--Se--C(7)H(7) with R = Bu, (t)Bu, Ph, 4-F--C(6)H(4) (12a,b,c,d) were prepared by the reaction of the corresponding silanes, Si(SeMe(3))(2) and R--Se--SiMe(3), respectively, with tropylium bromide C(7)H(7)Br. In spite of the low stability of the selanes even in dilute solutions and at low temperature, they could be characterised by their (1)H, (13)C and (77)Se NMR parameters. Coupling constants (1)J((77)Se,(13)C) were measured and calculated by DFT methods at the B3LYP/6-311+G(d,p) level of theory. The comparison of experimental and calculated coupling constants (1)J((77)Se,(13)C) included numerous selenium carbon compounds with largely different Se--C bonds, revealing a satisfactory agreement. Both the spin-dipole (SD) and the paramagnetic spin-orbital (PSO) terms contributed significantly to the spin-spin coupling interaction, in addition to the Fermi contact (FC) term.     

Measurement of the sign and the magnitude of heteronuclear coupling constants from spin-state-edited J-cross-polarization NMR experiments

New spin-state-selective (S3) NMR pulse sequences exclusively applying cross-polarization schemes to achieve optimum homonuclear and heteronuclear 1H-X coherence transfer are reported for the simple and accurate measurement of the magnitude and sign of heteronuclear coupling constants for samples at natural abundance. The proposed spin-edited HCP-TOCSY experiments are based on clean heteronuclear S3 excitation, generated by simultaneous co-addition of two independent in-phase and anti-phase components created during the mixing heteronuclear J-cross-polarization (HCP) step, which is finally transferred to other protons by a conventional homonuclear TOCSY mechanism. Selective 1D and non-selective 2D approaches for the easy determination of long-range proton-carbon and proton-nitrogen coupling constants on any protonated and non-protonated heteronuclei are presented and discussed for several organic molecules.