LR-selHSQMBC: Simultaneous Detection and Quantification of Very Weak Long-Range Heteronuclear NMR Correlations.

The optimum detection and accurate measurement of longer-range (4 J and higher) heteronuclear NMR correlations is described. The magnitude and/or the sign of a wide range of large and small long-range couplings can be simultaneously determined for protonated and non-protonated 13 C and 15 N nuclei using the LR-selHSQMBC experiment.

Measurement of long-range heteronuclear coupling constants using the peak intensity in classical 1D HMBC spectra.

In this contribution, we show that the magnitude of heteronuclear long-range coupling constants can be directly extracted from the classical 1D HMBC spectra, as all multiplet lines of a cross-peak always and exclusively vanish for the condition Δ = k/n JCH . To the best of our knowledge, this feature of the classical HMBC has not yet been noticed and exploited. This condition holds true, irrespective of the magnitude and numbers of additional active and passive homonuclear n JHH' couplings. Alternatively, the n JCH value may also be evaluated by fitting the peak's intensity in the individual spectra to its simple sin(πn JCH Δ)exp(-Δ/T2eff ) dependence. Compared to the previously proposed J-HMBC sequences that also use the variation of the cross-peak's intensity for extracting the coupling constants, the classical HMBC pulse sequence is significantly more sensitive.

Investigation of two- and three-bond carbon-hydrogen coupling constants in cinnamic acid based compounds.

Two- and three-bond coupling constants (2 JHC and 3 JHC ) were determined for a series of 12 substituted cinnamic acids using a selective 2D inphase/antiphase (IPAP)-single quantum multiple bond correlation (HSQMBC) and 1D proton coupled 13 C NMR experiments. The coupling constants from two methods were compared and found to give very similar values. The results showed coupling constant values ranging from 1.7 to 9.7 Hz and 1.0 to 9.6 Hz for the IPAP-HSQMBC and the direct 13 C NMR experiments, respectively. The experimental values of the coupling constants were compared with discrete density functional theory (DFT) calculated values and were found to be in good agreement for the 3 JHC . However, the DFT method under estimated the 2 JHC coupling constants. Knowing the limitations of the measurement and calculation of these multibond coupling constants will add confidence to the assignment of conformation or stereochemical aspects of complex molecules like natural products. Copyright © 2016 John Wiley & Sons, Ltd.

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 (n) J((1) H,(31) P), (n) J((1) H,(77) Se), and (n) J((1) H,(13) C) values, respectively.

Simultaneous determination of the magnitude and the sign of multiple heteronuclear coupling constants in 19F or 31P-containing compounds.

The presence of a highly abundant passive nucleus (Z = 19F or 31P) allows the simultaneous determination of the magnitude and the sign of up to three different heteronuclear coupling constants from each individual cross-peak observed in a 2D 1H-X selHSQMBC spectrum. Whereas J(HZ) and J(XZ) coupling constants are measured from E.COSY multiplet patterns, J(XH) is independently extracted from the complementary IPAP pattern generated along the detected F2 dimension. The incorporation of an extended TOCSY transfer allows the extraction of a complete set of all these heteronuclear coupling constants and their signs for an entire 1H subspin system. 1H-X/1H-Y time-shared versions are also proposed for the simultaneous measurement of five different couplings (J(XH), J(YH), J(XZ), J(YZ), and J(ZH)) for multiple signals in a single NMR experiment.

Implementing multiplicity editing in selective HSQMBC experiments.

Even C/CH(2) and odd CH/CH(3) carbon-multiplicity information can be directly distinguished from the relative positive/negative phase of cross-peaks in a novel ME (Multiplicity-Edited)-selHSQMBC experiment. The method can be extended by a TOCSY propagation step, and it is fully compatible for the simultaneous and precise determination of long-range heteronuclear coupling constants. Broadband homonuclear decoupling techniques can also be incorporated to enhance sensitivity and signal resolution by effective collapse of J(HH) multiplets.

Extending long-range heteronuclear NMR connectivities by HSQMBC-COSY and HSQMBC-TOCSY experiments.

The detection of long-range heteronuclear correlations presenting J(CH) coupling values smaller than 1-2Hz is a challenge in the structural analysis of small molecules and natural products. HSQMBC-COSY and HSQMBC-TOCSY pulse schemes are evaluated as complementary NMR methods to standard HMBC/HSQMBC experiments. Incorporation of an additional J(HH) transfer step in the basic HSQMBC pulse scheme can favor the sensitive observation of traditionally missing or very weak correlations and, in addition, facilitates the detection of a significant number of still longer-range connectivities to both protonated and non-protonated carbons under optimum sensitivity conditions. A comparative (1)H-(13)C study is performed using strychnine as a model compound and several examples are also provided including (1)H-(15)N applications.

Efficient and fast sign-sensitive determination of heteronuclear coupling constants.

Two complementary 1D NMR approaches for the fast and easy determination of the magnitude and the sign of heteronuclear J(XH) coupling constants are proposed: The Up&Down technique relies on the direct analysis of anti-phase multiplets whereas the Left&Right technique is based on the relative displacement between separate IPAP components.