Proton-proton Coupling Research Articles

Intermolecular hydrogen bond modulating the selective coupling of protons and CO2 to CH4 over nitrogen-doped carbon layers modified cobalt

Photocatalytic reduction of CO2 with H2O to CH4 is a promising route to migrate CO2 emission and complete the carbon neutrality goal. Nevertheless, one of the biggest challenges for this elegant strategy is that the coupling of the protons and CO2 to form CH4 is fiercely competed with proton-proton coupling to form H2, leading to extremely low CH4 selectivity. Herein, we designed and fabricated the nitrogen-doped carbon layers modified cobalt (N-C@Co) photocatalyst achieving the selective coupling of protons and CO2 to CH4 during photocatalytic reduction of CO2. The successful formation of intermolecular hydrogen bonds between the as-prepared N-C@Co and H2O molecule was found to suppress the mass transfer of the generated protons and promote the adsorption and activation of the CO2 molecule. More crucially, it was conducive to suppressing the desorption of the CO intermediate, which was typically deemed as the decisive species for CH4 generation. As a result, the H2 selectivity (9.0 %) and activity (17.3 µmol g−1) of the as-prepared N-C@Co were reduced by a factor of 9.3 and 17.6, respectively, as compared to that of bulk Co. The CH4 selectivity of N-C@Co was boosted 6.1 times from 13.3% of bulk Co to 81.3 % of N-C@Co with the generation rate of 155.7 μmol g−1 in 23 h. This work provides a new insight into the photocatalyst design for improving CH4 selectivity and suppressing the competing H2 and CO generation.

A DFT/machine-learning hybrid method for the prediction of 3 JHCCH couplings.

A machine learning model for the prediction of vicinal proton-proton couplings has been developed based on a hybrid representation that includes geometrical and electronic parameters derived from natural bond orbital (NBO) analysis of low-level BLYP/STO-3G computations. The model can predict 3 JHH couplings with accuracy comparable or better than the well-known Altona equation, and it can provide sensible 3 JHH predictions in systems not well handled by the Altona equation such as epoxide or cyclopropane rings.

Long-range coupling in cyclic silanes.

We report the synthesis of a mixed methyl- and hydro-substituted cyclosilane (1) possessing cis/trans stereoisomerism. Each diastereomer of 1 possesses distinct symmetry elements (cis-1: Cs-symmetric; trans-1: C2-symmetric). Cyclosilane 1 is a model system to probe configuration- and conformation-dependent long-range proton-proton coupling. Extensive NMR spectroscopic characterization is reported, including one-dimensional 1H NMR and 29Si DEPT and INEPT+ spectra and two-dimensional 1H-29Si and 1H-1H correlated spectroscopy (HSQC, HMBC, COSY). On the basis of these experiments, molecular connectivity consistent with four-bond 1H-1H coupling is confirmed.

Simultaneous Multi-Slice Selective Constant-Time J-Resolved Spectroscopy for Measuring J Values

Scalar coupling is an important parameter in nuclear magnetic resonance (NMR). The proton-proton coupling constant JH-H provides valuable information on molecular structure. However, determining JH-H value in complex coupling networks is still challenging. Here, we propose a method called simultaneous multi-slice selective constant-time J-resolved spectroscopy (SMS-SECTJRES) to measure JH-H values of all coupling networks of a molecule simultaneously in one experiment. In this method, gradient-encoded selective refocusing is used during a fixed evolution time, combined with echo planar spectroscopic imaging (EPSI) detection module to extract different selective J-edited spectra in different spatial positions. This new method is conducive to reveal coupling networks and the analysis of molecular structures.

PE-SERF: A sensitivity-improved experiment to measure JHH in crowded spectra.

Aiming at facilitating the analysis of molecular structure, the gradient-encoded selective refocusing methods (G-SERF) and a great number of its variants for measuring proton-proton coupling constants have been proposed. However, the sensitivity is an issue in the 2D gradient-encoded experiments, because the signal intensity is determined by the slice thickness of the sample that depends on encoding gradient and the bandwidth of selective pulses which is limited by the smallest chemical shift difference of any two coupled protons. Here, we present a method dubbed PE-SERF (perfect echo selective refocusing) which can determine all JHH values involving a selected proton with improved sensitivity compared to original G-SERF experiment. The modules of perfect echo involving selective pulses and gradient-encoded selective refocusing are combined in the method, so that the unwanted J couplings arising from coupled spin pairs in the same sample slice would be nullified. In this way, instead of single proton, a pair of coupled protons is allowed to share a sample slice, and thus the slice thickness can be increased and the spectral sensitivity can be improved. The performance of the method is demonstrated by experiments on quinine and strychnine.

Synthesis of new cyano-substituted analogues of Tröger's bases from bromo-derivatives. A stereochemical dependence of long-range (n JHH , n=4, 5, and 6) proton-proton and proton-carbon (n JCH , n=1, 2, 3, 4, and 5) coupling constants of these compounds.

A free-catalyst microwave-assisted cyanation of brominated Tröger's base derivatives (2a-f) is reported. The procedure is simple, efficient, and clean affording the nitrile compounds (3a-e, I) in very good yields. Complete assignment of 1 H and 13 C chemical shifts of 2a-f, I and 3a-d, I was achieved using gradient selected 1D nuclear magnetic resonance (NMR) techniques (1D zTOCSY, PSYCHE, DPFGSE NOE, and DEPT), homonuclear 2D NMR techniques (gCOSY and zTOCSY), and heteronuclear 2D NMR techniques (gHSQCAD/or pure-shift gHSQCAD, gHMBCAD, bsHSQCNOESY, and gHSQCAD-TOCSY) with adiabatic pulses. Determination of the long-range proton-proton coupling constants n JHH (n=4, 5, 6) was accomplished by simultaneous irradiation of two protons at appropriate power levels. In turn, determined coupling constants were tested by an iterative simulation program by calculating the 1 H NMR spectrum and comparing it to the experimental spectrum. The excitation-sculptured indirect-detection experiment (EXSIDE) and 1 H-15 N CIGARAD-HMBC (constant time inverse-detection gradient accordion rescaled heteronuclear multiple bond correlation) were applied for determination of long-range carbon-proton coupling constants n JCH (n=2, 3, and 4) and for assignment of 15 N chemical shift at natural abundance, respectively. DFT/B3LYP optimization studies were performed in order to determine the geometry of 2c using 6-31G(d,p), 6-311G(d,p), and 6-311+G(d,p) basis sets. For calculation of 1 H and 13 C chemical shifts, n JHH (n=2, 3, 4, 5, and 6), and n JCH (n=1, 2, 3, and 4) coupling constants, the GIAO method was employed at the B3LYP/6-31G(d,p), B3LYP/6-31+G(d,p), B3LYP/6-311+G(d,p), B3LYP/6-311++G(2d,2p), B3LYP/cc-pVTZ), and B3LYP/aug-cc-pVTZ) levels of theory. For the first time, a stereochemical dependence magnitude of the long-range n JHH (n=4, 5, and 6) and n JCH (n=1, 2, 3, 4, and 5) have been found in bromo-substituted analogues of Tröger's bases.

Quantitative 1H-1H Distances in Protonated Solids by Frequency-Selective Recoupling at Fast Magic Angle Spinning NMR.

Nuclear magnetic resonance (NMR) spectroscopy of protons in protonated solids is challenging. Fast magic angle spinning (MAS) and homonuclear decoupling schemes, in conjunction, with high magnetic fields have improved the proton resolution. However, experiments to quantitatively measure 1H-1H distances still remain elusive due to the dense proton-proton dipolar coupling network. A novel MAS solid-state NMR pulse sequence is proposed to selectively recouple and measure interproton distances in protonated samples. The phase-modulated sequence combined with a judicious choice of transmitter frequency is used to measure quantitative 1H-1H distances on the order of 3 Å in l-histidine·HCl·H2O, despite the presence of other strongly coupled protons. This method provides a major boost to NMR crystallography approaches for structural determination of pharmaceutical molecules by directly measuring 1H-1H distances. The band-selective nature of the sequence also enables observation of selective 1H-1H correlations (e.g., HN-HN/HN-Hα/ΗΝ-ΗMethyl) in peptides and proteins, which should serve as useful restraints in structure determination.

Replacement of the L-iduronic acid unit of the anticoagulant pentasaccharide idraparinux by a 6-deoxy-L-talopyranose \u2013 Synthesis and conformational analysis

One critical part of the synthesis of heparinoid anticoagulants is the creation of the L-iduronic acid building block featured with unique conformational plasticity which is crucial for the anticoagulant activity. Herein, we studied whether a much more easily synthesizable sugar, the 6-deoxy-L-talose, built in a heparinoid oligosaccharide, could show a similar conformational plasticity, thereby can be a potential substituent of the L-idose. Three pentasaccharides related to the synthetic anticoagulant pentasaccharide idraparinux were prepared, in which the L-iduronate was replaced by a 6-deoxy-L-talopyranoside unit. The talo-configured building block was formed by C4 epimerisation of the commercially available L-rhamnose with high efficacy at both the monosaccharide and the disaccharide level. The detailed conformational analysis of these new derivatives, differing only in their methylation pattern, was performed and the conformationally relevant NMR parameters, such as proton-proton coupling constants and interproton distances were compared to the corresponding ones measured in idraparinux. The lack of anticoagulant activity of these novel heparin analogues could be explained by the biologically not favorable 1C4 chair conformation of their 6-deoxy-L-talopyranoside residues.

Why is HMBC superior to LR-HSQC? Influence of homonuclear couplings JHH' on the intensity of long-range correlations.

Long-range heteronuclear single quantum correlation (LR-HSQC) experiments may be applied as an alternative to heteronuclear multiple-bond correlation (HMBC) experiments for detecting long-range correlations but has never enjoyed popularity for that purpose. To the best of our knowledge, the exact reasons have not yet been fully established. For both experiments, it is widely accepted that the evolution of proton-proton homonuclear couplings JHH' during the polarization transfer delays Δ leads to significant losses, and that the intensity of the observable coherence is zero when JHH' matches the condition Δ=0.5/JHH' . Here, we analyze the influence of JHH' on the intensity of long-range correlations in HMBC and LR-HSQC spectra. We show that for both experiments long-range correlations will not be canceled because of homonuclear couplings JHH' . Our theoretical and experimental results definitely establish and validate the superiority of HMBC-based experiments among the family of heteronuclear long-range correlation experiments: (a) the overall cross peak's intensity is higher, and (b) in LR-HSQC experiments, the intensity of the long-range cross peaks is additionally influenced in an unwanted way by the magnitude and number of passive homonuclear proton-proton couplings JHH' .

Incorporating BIRD‐based homodecoupling in the dual‐optimized, inverted 1JCC 1,n‐ADEQUATE experiment

1,n-ADEQUATE is a powerful NMR technique for elucidating the structure of proton-deficient small molecules that can help establish the carbon skeleton of a given molecule by providing long-range three-bond 13 C─13 C correlations. Care must be taken when using the experiment to identify the simultaneous presence of one-bond 13 C─13 C correlations that are not filtered out, unlike the HMBC experiment that has a low-pass J-filter to filter 1 JCH responses out. Dual-optimized, inverted 1 JCC 1,n-ADEQUATE is an improved variant of the experiment that affords broadband inversion of direct responses, obviating the need to take additional steps to identify these correlations. Even though ADEQUATE experiments can now be acquired in a reasonable amount of experimental time if a cryogenic probe is available, low sensitivity is still the main impediment limiting the application of this elegant experiment. Here, we wish to report a further refinement that incorporates real-time bilinear rotation decoupling-based homodecoupling methodology into the dual-optimized, inverted 1 JCC 1,n-ADEQUATE pulse sequence. Improved sensitivity and resolution are achieved by collapsing homonuclear proton-proton couplings from the observed multiplets for most spin systems. The application of the method is illustrated with several model compounds.

Dictyoneolone, a B/C ring juncture-defused steroid from a Dictyonella sp. sponge

Dictyoneolone (1), a new secosteroid was isolated from a Dictyonella sp. sponge collected from Gageo-do, Korea. Based upon the results of combined spectroscopic analyses, the structure of this compound was determined to possess a highly unusual B/C ring juncture-defused moiety. The configurations of 1 were determined by a combination of proton-proton couplings and NOESY analyses. Dictyoneolone exhibited weak cytotoxicity against the K562 and A549 cancer cell lines.

Combining Fourier phase encoding and broadband inversion toward J-edited spectra

Nuclear magnetic resonance (NMR) spectra are often utilized for gathering accurate information relevant to molecular structures and composition assignments. In this study, we develop a homonuclear encoding approach based on imparting a discrete phase modulation of the targeted cross peaks, and combine it with a pure shift experiments (PSYCHE) based J-modulated scheme, providing simple 2D J-edited spectra for accurate measurement of scalar coupling networks. Chemical shifts and J coupling constants of protons coupled to the specific protons are demonstrated along the F2 and F1 dimensions, respectively. Polychromatic pulses by Fourier phase encoding were performed to simultaneously detect several coupling networks. Proton-proton scalar couplings are chosen by a polychromatic pulse and a PSYCHE element. Axis peaks and unwanted couplings are complete eradicated by incorporating a selective COSY block as a preparation period. The theoretical principles and the signal processing procedure are laid out, and experimental observations are rationalized on the basis of theoretical analyses.

Molecules as networks: A localization-delocalization matrices approach

Inspired by chemical graph theory (CGT), a matrix representation of molecules and reaction paths is presented within the framework of Bader’s quantum theory of atoms in molecules (QTAIM). A molecule is viewed as a network of electron delocalization channels or highways (vertices) that connect every pair of atoms in the system and electron localization cul-de-sacs loops connecting any given atom to itself. The representation of a molecule as a fuzzy, complete, non-directed graph, captured mathematically as an electron localization-delocalization matrix (an LDM), is rich with coded physical and chemical information. An LDM contains information on the bond-path molecular graph, bond strengths, molecular geometry, atomic electron populations and atomic charges, newly proposed multidimensional atomic charges, atomic volumes, free valences, NMR proton-proton coupling constants, and molecular branching. LDMs can quantify molecular (di)similarity by matrix difference measures such as the Frobenius distance, possibly after diagonalization and/or size adjustments with ghost atoms, or by the use of principal component analysis (PCA). Because they condense information at an atomic resolution, LDMs can be used to construct predictive quantitative-structure-to-activity/property-relationship (QSAR/QSPR) models with a wide range of applications including, for example, thermochemical properties, stress-corrosion cracking inhibitors’ activity, mosquito repellency, ribotoxicity, pKa's, aromaticity of rings-in-molecules, etc. The LDM philosophy can be extended to other properties that associate to each atom a “self” term and a sum of “interaction” terms with every other atom in the system. Such properties include the Oviedo Group’s “interacting quantum atoms” (IQAs) atomic energy decomposition and the integrated Bader-Gatti source function. The potential uses and connections between these different matrix representations of a molecule are explored. The coarse graining of LDMs to possibly compare macromolecular structures is also briefly discussed.

A simultaneous multi-slice selective J-resolved experiment for fully resolved scalar coupling information

Proton-proton scalar coupling plays an important role in molecular structure elucidation. Many methods have been proposed for revealing scalar coupling networks involving chosen protons. However, determining all JHH values within a fully coupled network remains as a tedious process. Here, we propose a method termed as simultaneous multi-slice selective J-resolved spectroscopy (SMS-SEJRES) for simultaneously measuring JHH values out of all coupling networks in a sample within one experiment. In this work, gradient-encoded selective refocusing, PSYCHE decoupling and echo planar spectroscopic imaging (EPSI) detection module are adopted, resulting in different selective J-edited spectra extracted from different spatial positions. The proposed pulse sequence can facilitate the analysis of molecular structures. Therefore, it will interest scientists who would like to efficiently address the structural analysis of molecules.

2JHH-resolved HSQC: Exclusive determination of geminal proton-proton coupling constants

The measurement of two-bond proton-proton coupling constants (2JHH) in prochiral CH2 groups from the F2 dimension of 2D spectra is not easy due to the usual presence of complex multiplet J patterns, line broadening effects and strong coupling artifacts. These drawbacks are particularly pronounced and frequent in AB spin systems, as those normally exhibited by the pair of diastereotopic CH2 protons. Here, a novel 2JHH-resolved HSQC experiment for the exclusive and accurate determination of the magnitude of 2JHH from the doublet displayed along the highly-resolved indirect F1 dimension is described. A pragmatic 2JHH NMR profile affords a fast overview of the full range of existing 2JHH values. In addition, a 2JHH/δ(13C)-scaled version proves to be an efficient solution when severe signal overlapping complicate a rigorous analysis. The performance of the method is compared with other current techniques and illustrated by the determination of challenging residual dipolar 2DHH coupling constants of small molecules dissolved in weakly orienting media.

Quest for hydrogen environments in hydrogen-bonded systems

We performed proton high-resolution nuclear magnetic resonance (NMR) measurements on KH2PO4 ferroelectrics. The 1H high-resolution NMR measurements were performed using the magic-angle spinning technique, which removes the proton-proton dipolar coupling and the chemical shift anisotropy in solid-state materials. High-resolution magic-angle spinning 1H NMR spectroscopy provides information on the chemical structure in the KH2PO4 system. From the measured chemical shift data, we determined the oxygen separation distance of the O-H···O hydrogen bond. The localized hydrogen position of the environments near heavy atoms can be depicted using Morse potentials, which provide the wave function of the eigenstate and the probability distribution of hydrogen in the local structure based on the solutions of the Schr¨odinger equation.

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 (JHH ) 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 JHH 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. Copyright © 2016 John Wiley & Sons, Ltd.

Measuring JHH values with a selective constant-time 2D NMR protocol

Proton-proton scalar couplings play important roles in molecule structure elucidation. However, measurements of JHH values in complex coupled spin systems remain challenging. In this study, we develop a selective constant-time (SECT) 2D NMR protocol with which scalar coupling networks involving chosen protons can be revealed, and corresponding JHH values can be measured through doublets along the F1 dimension. All JHH values within a network of n fully coupled protons can be separately determined with (n−1) SECT experiments. Additionally, the proposed pulse sequence possesses satisfactory sensitivity and handy implementation. Therefore, it will interest scientists who intend to address structural analyzes of molecules with overcrowded spectra, and may greatly facilitate the applications of scalar-coupling constants in molecule structure studies.

Callyazepin and (3R)-Methylazacyclodecane, Nitrogenous Macrocycles from a Callyspongia sp. Sponge.

Callyazepin (1) and (3R)-methylazacyclodecane (2), nitrogenous macrocycles, were isolated from a tropical Callyspongia sp. sponge. The combined spectroscopic analyses revealed that the structure of 1 is a bicyclic azepane ammonium salt of a novel structural class derived from mixed biogenetic origins. The configuration of the whole molecule and the conformation of the formamide group were assigned by proton-proton coupling constants, a NOESY analysis, and the application of the phenylglycine methyl ester method. The structure of 2 was identified using combined spectroscopic analyses and ECD measurements. These compounds exhibited moderate cytotoxic activities against the K562 and A549 cell lines.

Relativistic Force Field: Parametrization of (13)C-(1)H Nuclear Spin-Spin Coupling Constants.

Previously, we reported a reliable DU8 method for natural bond orbital (NBO)-aided parametric scaling of Fermi contacts to achieve fast and accurate prediction of proton-proton spin-spin coupling constants (SSCC) in (1)H NMR. As sophisticated NMR experiments for precise measurements of carbon-proton SSCCs are becoming more user-friendly and broadly utilized by the organic chemistry community to guide and inform the process of structure determination of complex organic compounds, we have now developed a fast and accurate method for computing (13)C-(1)H SSCCs. Fermi contacts computed with the DU8 basis set are scaled using selected NBO parameters in conjunction with empirical scaling coefficients. The method is optimized for inexpensive B3LYP/6-31G(d) geometries. The parametric scaling is based on a carefully selected training set of 274 ((3)J), 193 ((2)J), and 143 ((1)J) experimental (13)C-(1)H spin-spin coupling constants reported in the literature. The DU8 basis set, optimized for computing Fermi contacts, which by design had evolved from optimization of a collection of inexpensive 3-21G*, 4-21G, and 6-31G(d) bases, offers very short computational (wall) times even for relatively large organic molecules containing 15-20 carbon atoms. The most informative SSCCs for structure determination, i.e., (3)J, were computed with an accuracy of 0.41 Hz (rmsd). The new unified approach for computing (1)H-(1)H and (13)C-(1)H SSCCs is termed "DU8c".