Homonuclear and Heteronuclear coupling constants

How to measure long-range proton-carbon coupling constants from 1H-selective HSQMBC experiments

Heteronuclear long‐range scalar coupling constants (ⁿJ_CH) are a valuable tool for solving problems in organic chemistry and are especially suited for stereochemical and configurational analyses of small molecules and natural products. This tutorial will focus on the step‐by‐step implementation of several 2D ¹H frequency selective HSQMBC experiments for the easy and accurate measurement of either the magnitude or both the magnitude and the sign of long‐range ⁿJ_CH couplings. The performance of these experiments will be showcased with several scenarios in a range of different experimental conditions.

Highly resolved HSQC experiments for the fast and accurate measurement of homonuclear and heteronuclear coupling constants

A number of J-upscaled NMR experiments are currently available to measure coupling constants along the indirect F1 dimension of a 2D spectrum. A major drawback is the limited F1 digital resolution that requires long acquisition times in order to achieve reasonably accurate measures. Here is shown how high levels of F1 digital resolution in a multiple-purpose HSQC experiment can be easily achieved by implementing a general J/d-scaling strategy. In particular, a set of new J-resolved HSQC experiments is presented for a faster and much more accurate J determination in small molecules. Several options and practical aspects are discussed and exemplified by measuring the magnitude and/or the sign of several homo- and heteronuclear coupling constants in one shot.

1JCH NMR Profile: Identification of key structural features and functionalities by visual observation and direct measurement of one-bond proton-carbon coupling constants

A user-friendly NMR interface for the visual and accurate determination of experimental one-bond proton-carbon coupling constants (1JCH) in small molecules is presented. This intuitive 1JCH profile correlates directly to δ(1H), and 1JCH facilitates the rapid identification and assignment of 1H signals belonging to key structural elements and functional groups. Illustrative examples are provided for some target molecules, including terminal alkynes, strained rings, electronegative substituents, or lone-pair-bearing heteronuclei.

Accurate measurement of JHH in overlapped signals by a TOCSY-edited SERF Experiment

Selective refocusing (GSERF or the recent PSYCHEDELIC) experiments were originally designed to determine all proton–proton coupling constants (J_HH) for a selected proton resonance. They work for isolated signals on which selective excitation can be successfully applied but, as it happens in other selective experiments, fail for overlapped signals. To circumvent this limitation, a doubly‐selective TOCSY‐GSERF scheme is presented for the measurement of J_HH in protons resonating in crowded regions. This new experiment takes advantage of the editing features of an initial TOCSY transfer to uncover hidden resonances that become accessible to perform the subsequent frequency‐selective refocusing.

Long-Range Proton-Carbon Coupling Constants: NMR Methods and applications

A general review of novel NMR methods to measure heteronuclear long-range proton–carbon coupling constants (ⁿJ_CH; n > 1) in small molecules is made. NMR experiments are classified in terms of NMR pulse scheme and cross-peak nature. A discussion about simplicity, general applicability and accuracy for each particular NMR experiment is presented and exemplified. Important aspects such as the sign determination and measurement of very small coupling values involving protonated and non-protonated carbons as well as the complementarity between different experiments are also discussed. Finally, a compilation of applications in structural and conformational analysis of different types of molecules since 2000 is surveyed.

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 = ¹⁹ F 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.

Straightforward measurement of individual 1J(CH) and 2J(HH) in diastereotopic CH2 groups

The C–HA cross-peak corresponding to a diastereotopic CHAHB methylene spin system exhibits a characteristic 1:0:1 multiplet pattern along the indirect dimension of a x1-coupled HSQC spectrum. It is shown here that the use of the initial 13C Boltzmann polarization instead of the regular INEPT-based 1H Boltzmann polarization makes visible the central lines of this multiplet pattern. A spin-state-selective method is proposed for the efficient measurement of both 1J(CHA) and 1J(CHB) along the indirect dimension of a 2D spectrum as well as to the magnitude and the sign of the geminal 2J(HAHB) coupling constant from the straightforward analysis of a single four-component E.COSY cross-peak. Additionally, the extraction of 1J(CH) values for CH and CH3 multiplicities can be also performed from the same spectrum. The success of the method is also illustrated for the determination of residual dipolar 1D(CH) and 2D(HH) coupling constants in a small molecule weakly aligned in a PMMA swollen gel.

On the interference of J(HH) modulation in HSQMBC-IPAP and HMBC-IPAP experiments

The effects of phase modulation due to homonuclear proton–proton coupling constants in HSQMBC-IPAP and HMBC-IPAP experiments are experimentally evaluated. We show that accurate values of small proton–carbon coupling constants, nJCH, can be extracted even for phase-distorted cross-peaks obtained from a selHSQMBC experiment applied simultaneously on two mutually J-coupled protons. On the other hand, an assessment of the reliability of nJCH measurement from distorted cross-peaks obtained in broadband IPAP versions of equivalent HMBC and HSQMBC experiments is also presented. Finally, we show that HMBC-COSY experiments could be an excellent complement to HMBC for the measurement of small nJCH values.

Simultaneous measurement of J(HH) and two different nJ(CH) coupling constants from a single multiply edited 2D cross-peak

Three different J-editing methods (IPAP, E.COSY and J-resolved) are implemented in a single NMR experiment to provide spinstate- edited 2D cross-peaks from which a simultaneous measurement of different homonuclear and heteronuclear coupling constants can be performed. A new J-selHSQMBC-IPAP experiment is proposed for the independent measurement of two different nJ(CH) coupling constants along the F2 and F1 dimensions of the same 2D cross-peak. In addition, the E.COSY pattern provides additional information about the magnitude and relative sign between J(HH) and nJ(CH) coupling constants.