Scalar Coupling Constants Research Articles

The role of intra and intermolecular interactions on the conformational dynamics of 2-halo-1-phenylpropanols: Structure and solvent effects

Experimental and theoretical 3JHH scalar coupling constants allowed the identification of the conformational landscape of erythro (eX) and threo (tX) 2-halo-1-phenylpropanols (halo = F, Cl, and Br). NMR scalar coupling constants captured dynamics of the OC-C-X dihedral and OH rotameric states, in a dynamic and solvent-dependent equilibrium. The erythro series revealed a particular halogen-dependent equilibrium, which showed different sensitivity to the media, especially in acetone, where the eF populations were completely shifted. At the same time, threo showed a highly solvent-sensitive equilibrium. NBO calculations showed the importance of electron delocalization over steric and electrostatic effects to stabilize the preferred synclinal conformer in both diastereomers. A Principal Component Analysis (PCA) on the NBO stabilization energies pointed to a complex mixture of electronic delocalization happening simultaneously. Hyperconjugative interactions are significant, but they are not the only important effect. Non-covalent interactions were also identified through NCI surfaces. Hydrogen bonds and intramolecular C-X···π and CH···π interactions were proved to act differently in the two diastereomers, affecting their equilibria in different ways. Nuclear Overhauser (NOE) NMR experiments point to an intramolecular CH···π contact, while 1H NMR of the aromatic hydrogens evidence an intermolecular effect of acetone and DMSO on the phenyl ring. DFT with explicit solvation shows a solvent shell favoring intermolecular CH···π contacts, in agreement with the experiments. This thorough analysis revealed that intra- and intermolecular factors contribute to the preference for the synclinal conformer in the studied compounds.

Revealing elusive conformations of sucrose from hydrogen bond J-coupling in H2O: A combined NMR and quantum mechanics study.

Hydrogen bonding is a crucial feature of biomolecules, but its characterization in glycans dissolved in aqueous solutions is challenging due to rapid hydrogen exchange between hydroxyl groups and H2O. In principle, the scalar (J) coupling constant can reveal the relative orientation of the atoms in the molecule. In contrast to J-coupling through H-bonds reported in proteins and nucleic acids, research on J-coupling through H-bonds in glycans dissolved in water is lacking. Here, we use sucrose as a model system for H-bonding studies; its structure, which consists of glucose (Glc) and fructose (Frc), is well-studied, and it is readily available. We apply the in-phase, antiphase-HSQC-TOCSY and quantify previously unreported through H-bond J-values for Frc-OH1-Glc-OH2 in H2O. While earlier reports of Brown and Levy indicate this H-bond as having only a single direction, our reported findings indicate the potential presence of two involving these same atoms, namely, G2OH➔F1O and F1OH➔G2O (where F and G stand for Frc and Glc, respectively). The calculated density functional theory J-values for the G2OH➔F1O agree with the experimental values. Additionally, we detected four other possible H-bonds in sucrose, which require different phi, psi (ϕ, ψ) torsion angles. The ϕ, ψ values are consistent with previous predictions of du Penhoat et al. and Venable et al. Our results will provide new insights into the molecular structure of sucrose and its interactions with proteins.

Conformational Landscape of α-Halopropiophenones Determined by nJC-H NMR Reveals Unexpected Patterns and Geometric Constraints.

The conformational features of α-halopropiophenones were investigated to understand the influence of α-halogens on conformation through hyperconjugative interactions, electrostatics, and steric factors. Using NMR, C-H scalar coupling constants were measured in different solvents, revealing a pattern in the conformational equilibria, which we validated by computational means. This behavior arises largely from hyperconjugative effects with the exception of the fluoro-derivatives, which are also influenced by steric and electrostatic interactions. In all cases, the contribution to hyperconjugation of the α-halo ketones is driven by the oxygen lone pair (rather than the C-X bond), which donates electron density to the adjacent C-C bonds. Additionally, C-Cα bond rotation generates distortions in the side chain, responsible for destabilization, thus affecting system conjugation. These structural features identified for the α-halo ketones are also reflected in their reactivity, which is distinct from that expected for nucleophilic addition.

Klein–Gordon oscillator under gravitational effects in a topologically charged Ellis–Bronnikov wormhole

In this paper, we investigate the phenomenon of a relativistic quantum oscillator in non-massive wormhole spacetime, known in the literature as Ellis–Bronnikov-type wormhole, for a spin-zero particle subjected to the effects of a scalar field. We have obtained analytically the bound state solutions and your respective energy spectrum. The energy profile of this scalar field is modified by the wormhole throat as well as the scalar coupling constant of curvature. In the second part of the work, we investigate how the energy spectrum for a spin-zero particle is modified by an Aharonov–Bohm geometric phase effect. We also built a graphical representation to try to visualize this modification generated by the magnetic flux constant.

J-filter: An experiment to simplify and isolate specific signals in 1 H NMR spectra of complex mixtures based on scalar coupling constants.

One-dimensional selective NMR experiments relying on a J-filter element are proposed to isolate specific signals in crowded 1 H spectral regions. The J-filter allows the edition or filtering of signals in a region of interest of the spectrum by exploiting the specific values of their 1 H-1 H coupling constants and certain parameters of protons coupled to them that appear in less congested parts of the spectrum (chemical shifts and coupling constants). The new experiments permitted the isolation of specific peaks of phytosterol components in a sample obtained from a liquid nutraceutical recommended for lowering blood cholesterol levels in regions with complete overlap in the 1 H spectrum.

Rapid Measurement of Heteronuclear Coupling Constants in Complex NMR Spectra.

The NMR analysis of fluorine-containing molecules, increasingly widespread due to their importance in pharmaceuticals and biochemistry, poses significant challenges. Severe peak overlap in the proton spectrum often hinders the extraction of critical structural information in the form of heteronuclear scalar coupling constants, which are crucial for determining pharmaceutical properties and biological activity. Here, a new method, IPAP-FESTA, is reported that drastically simplifies measurements of the signs and magnitudes of proton-fluorine couplings. Its usefulness is demonstrated for the structural study of the steroidal drug fluticasone propionate extracted from a commercial formulation and for assessing solvent effects on the conformational equilibrium in a physically inseparable fluorohydrin mixture.

Dipole Cooperativity and Polarization Frustration Determine the Secondary Structure Distribution of Short Alanine Peptides in Water.

The physical driving forces for secondary structure preferences of hydrated alanine peptide are investigated with B3LYP-D3(BJ) and the adaptive force matching (AFM) method. The AFM fit to the DFT surface, ALA2022, provides excellent agreement with the nuclear magnetic resonance scalar coupling constants from experiments. In turn, the model is used to gain insight into the physical driving forces behind secondary structure preferences of hydrated peptides. DFT calculations with and without the Conductor-like Screening Model (COSMO) show that the α helix is stabilized by solvent polarization due to dipole cooperativity. The two adjacent amide groups in β strand form a near-planar trapezoid that is not much larger than the size of water molecules. When the finite size of a water molecule is considered, the stabilization from solvent polarization for such a trapezoid is frustrated. Water molecules cannot find orientations to properly stabilize all four polar regions close to each other with such an awkward arrangement. This leads to quite substantial reduction in polarization stabilization. Although the polyproline II (PP-II) conformation is very similar to the β strand, the small twist in the backbone angles allowed much improved polarization stabilization. The improved polarization, when combined with favorable intrapeptide interactions, leads to the PP-II to be lowest in free energy. Other factors, such as the entropic TΔS and the ϕ, ψ coupling terms, are also studied but are found to play only a minor role. The insight shown in this work helps to better understand the structure of globular and intrinsic disordered proteins and facilitate future force field development.

Glycosidic α-linked mannopyranose disaccharides: an NMR spectroscopy and molecular dynamics simulation study employing additive and Drude polarizable force fields.

D-Mannose is a structural component in N-linked glycoproteins from viruses and mammals as well as in polysaccharides from fungi and bacteria. Structural components often consist of D-Manp residues joined via α-(1→2)-, α-(1→3)-, α-(1→4)- or α-(1→6)-linkages. As models for these oligo- and polysaccharides, a series of mannose-containing disaccharides have been investigated with respect to conformation and dynamics. Translational diffusion NMR experiments were performed to deduce rotational correlation times for the molecules, 1D 1H,1H-NOESY and 1D 1H,1H-T-ROESY NMR experiments were carried out to obtain inter-residue proton-proton distances and one-dimensional long-range and 2D J-HMBC experiments were acquired to gain information about conformationally dependent heteronuclear coupling constants across glycosidic linkages. To attain further spectroscopic data, the doubly 13C-isotope labeled α-D-[1,2-13C2]Manp-(1→4)-α-D-Manp-OMe was synthesized thereby facilitating conformational analysis based on 13C,13C coupling constants as interpreted by Karplus-type relationships. Molecular dynamics simulations were carried out for the disaccharides with explicit water as solvent using the additive CHARMM36 and Drude polarizable force fields for carbohydrates, where the latter showed broader population distributions. Both simulations sampled conformational space in such a way that inter-glycosidic proton-proton distances were very well described whereas in some cases deviations were observed between calculated conformationally dependent NMR scalar coupling constants and those determined from experiment, with closely similar root-mean-square differences for the two force fields. However, analyses of dipole moments and radial distribution functions with water of the hydroxyl groups indicate differences in the underlying physical forces dictating the wider conformational sampling with the Drude polarizable versus additive C36 force field and indicate the improved utility of the Drude polarizable model in investigating complex carbohydrates.

From Relative to Absolute Stereochemistry of Secondary Metabolites: Applications in Plant Chemistry

Structural elucidation of specialized metabolites or natural plant products, especially the stereochemical features of chiral bioactive metabolites, is the most important stage for all investigations in pharmacognosy and phytochemistry. Numerous methods have been established to solve the absolute configuration of natural products, including direct methods such as X-ray diffraction, chiroptical spectroscopy, stereo-controlled partial or total organic synthesis, and chemical correlation by simple organic reactions for derivatization, as well as indirect methods using a standard chiral compound or a derivatizing agent with known absolute configuration, for example, nuclear magnetic resonance by utilization of anisotropic effects of chiral agents. Once the relative configuration of a natural product is resolved, the absolute stereochemistry can be determined with the assistance of chiroptical spectroscopies supported by quantum mechanical-NMR prediction of chemical shifts, scalar coupling constants and simulation of optical rotatory dispersion, in addition to electronic and vibrational circular dichroism spectra. This review summarizes the most practical methods employed in the assignment of absolute stereochemistry of natural plant products with selected examples focused on multichiral center bioactive small molecules from the mega-diverse Brazilian and Mexican flora.

Probabilistic Interpretation of NMR J-Couplings Determines BI-BII State Equilibria in DNA.

Interpretation of 3JP,H3' NMR scalar spin-spin coupling constants in DNA becomes more reliable by including distinct structural states such as BI and BII, using the weighted-static or, better still, the recently implemented adiabatic-MD (Ad-MD) method. The calculation method employs an adiabatic ("Ad") dependence of 3JP,H3' coupling on NMR-assigned torsion angle, ε, weighted by P(ε) probability distribution calculated by molecular dynamics (MD). Ad-MD calculations enable cross-validation of the bsc1, OL15, and OL21 force fields and various parametrizations of the Karplus equation describing the dependence of 3JP,H3' coupling on ε torsion (KE). The mean absolute deviation of Ad-MD 3JP,H3' couplings from the experimental values in Dickerson-Drew DNA is comparable to the scatter of 3JP,H3' couplings among four separate NMR experiments. A commonly accepted assumption of homogeneity of one kind of structure-dynamic state within DNA (BI or BII) is questionable because the principal characteristics of relevant P(ε) probabilities (shapes and positioning) vary with DNA sequence. The theory outlined in the present work sets limits to future reparameterization of MD force fields, as relevant to NMR data.

Fermionic vacuum polarization induced by a non-Abelian vortex

In this paper, we analyze the fermionic condensate (FC) and the vacuum expectation value (VEV) of the energy–momentum tensor associated with an iso-spin-[Formula: see text] charged massive fermionic field induced by the presence of a [Formula: see text] vortex, taking into account the effect of the conical geometry produced by this object. We consider the vortex as an idealized topological defect, i.e. very thin, straight and carrying a magnetic flux running along its core. Besides the direct coupling of the fermionic field with the iso-vector gauge field, we also admit the coupling with the scalar sector of the non-Abelian vortex system, expressed as a vector in the three-dimensional iso-space. Due to this interaction, the FC is expressed as the sum of two contributions associated with the two different effective masses for the [Formula: see text] fermionic components of the iso-spin operator, [Formula: see text]. The VEV of the energy tensor also presents a similar structure. The vacuum energy density is equal to the radial and axial stresses. As to the azimuthal one, it is expressed in terms of the radial derivative of energy density. Regarding the magnetic flux, both the FC and the VEV of the energy–momentum tensor can be positive or negative. Another interesting consequence of the interaction with the bosonic sector, the FC and VEV of the energy–momentum tensor, presents different intensity for different values of the ratio between the scalar coupling constant and the mass of the fermionic field. This is a new feature presented by the system.

Prediction of chemical shift in NMR: A review.

Calculation of solution-state NMR parameters, including chemical shift values and scalar coupling constants, is often a crucial step for unambiguous structure assignment. Data-driven (sometimes called empirical) methods leverage databases of known parameter values to estimate parameters for unknown or novel molecules. This is in contrast to popular ab initio techniques that use detailed quantum computational chemistry calculations to arrive at parameter estimates. Data-driven methods have the potential to be considerably faster than ab inito techniques and have been the subject of renewed interest over the past decade with the rise of high-quality databases of NMR parameters and novel machine learning methods. Here, we review these methods, their strengths and pitfalls, and the databases they are built on.

New effective interactions for hypernuclei in a density-dependent relativistic mean field model

New effective $\Lambda N$ interactions are proposed for the density dependent relativistic mean field model. The multidimensionally constrained relativistic mean field model is used to calculate ground state properties of eleven known $\Lambda$ hypernuclei with $A\ge 12$ and the corresponding core nuclei. Based on effective $NN$ interactions DD-ME2 and PKDD, the ratios $R_\sigma$ and $R_\omega$ of scalar and vector coupling constants between $\Lambda N$ and $NN$ interactions are determined by fitting calculated $\Lambda$ separation energies to experimental values. We propose six new effective interactions for $\Lambda$ hypernuclei: DD-ME2-Y1, DD-ME2-Y2, DD-ME2-Y3, PKDD-Y1, PKDD-Y2 and PKDD-Y3 with three ways of grouping and including these eleven hypernuclei in the fitting. It is found that the two ratios $R_\sigma$ and $R_\omega$ are correlated well and there holds a good linear relation between them. The statistical errors of the ratio parameters in these effective interactions are analyzed. These new effective interactions are used to study the equation of state of hypernuclear matter and neutron star properties with hyperons.

Stereoisomerism in Tetrametallic Propeller‐Like Complexes: A Solid‐State and Solution NMR Study on a Tetragallium(III) Derivative

AbstractTetragallium(III) complex in [Ga4(L4‐Py)2(dpm)6] ⋅ EtOH, with H3L4‐Py=2‐(hydroxymethyl)‐2‐(pyridin‐4‐yl)propane‐1,3‐diol and Hdpm=dipivaloylmethane, was investigated as a diamagnetic analogue of tetrametallic, propeller‐like single‐molecule magnets (SMMs). The chiral molecular structure partitions the six CH2 protons of each tripodal (L4‐Py)3− ligand into two diastereotopic sets. The two signals were clearly detected by 1H NMR spectroscopy in C6D6, proving that Λ and Δ enantiomers interconvert slowly over NMR timescale. Density functional theory calculations provided quantitative agreement with the observed values of chemical shifts and scalar coupling constants across both geminal and long‐range interaction pathways. The solid‐state structure suggests the occurrence of a lower symmetry stereoisomer (27 mol%), which was clearly identified in the NMR spectra. Since high spin Fe3+ forms distinctly more inert complexes than Ga3+, comparable or greater configurational stability is expected for the isostructural FeIII4, FeIII3CrIII, and FeIII3VIII SMMs, which are difficult to investigate by solution NMR because of the strong paramagnetism.

Predicting scalar coupling constants by graph angle-attention neural network

Scalar coupling constant (SCC), directly measured by nuclear magnetic resonance (NMR) spectroscopy, is a key parameter for molecular structure analysis, and widely used to predict unknown molecular structure. Restricted by the high cost of NMR experiments, it is impossible to measure the SCC of unknown molecules on a large scale. Using density functional theory (DFT) to theoretically calculate the SCC of molecules is incredibly challenging, due to the cost of substantial computational time and space. Graph neural networks (GNN) of artificial intelligence (AI) have great potential in constructing molecular-like topology models, which endows them the ability to rapidly predict SCC through data-driven machine learning methods, and avoiding time-consuming quantum chemical calculations. With a priori knowledge of angles, we propose a graph angle-attention neural network (GAANN) model to predict SCC by means of some easily accessible related information. GAANN, with a multilayer message-passing network and a self-attention mechanism, can accurately simulate the molecular-like topological structure and predict molecular properties. Our simulations show that the prediction accuracy by GAANN, with the log(MAE) = −2.52, is close to that by DFT calculations. Different from conventional AI methods, GAANN combining the AI method with quantum chemistry theory (Karplus equation) has a strong physicochemical interpretability about angles. From an AI perspective, we find that bond angle has the highest correlation with the SCC among all angle features (dihedral angle, bond angle, geometric angles) about multiple coupling types in the small molecule datasets.

NMR Properties of the Cyanide Anion, a Quasisymmetric Two-Faced Hydrogen Bonding Acceptor

The isotopically enriched cyanide anion, (13C≡15N)−, has a great potential as the NMR probe of non-covalent interactions. However, hydrogen cyanide is highly toxic and can decompose explosively. It is therefore desirable to be able to theoretically estimate any valuable results of certain experiments in advance in order to carry out experimental studies only for the most suitable molecular systems. We report the effect of hydrogen bonding on NMR properties of 15N≡13CH···X and 13C≡15NH···X hydrogen bonding complexes in solution, where X = 19F, 15N, and O=31P, calculated at the ωB97XD/def2tzvp and the polarizable continuum model (PCM) approximations. In many cases, the isotropic 13C and 15N chemical shieldings of the cyanide anion are not the most informative NMR properties of such complexes. Instead, the anisotropy of these chemical shieldings and the values of scalar coupling constants, including those across hydrogen bonds, can be used to characterize the geometry of such complexes in solids and solutions. 1J(15N13C) strongly correlates with the length of the N≡C bond.

Probing Halogen Bonds by Scalar Couplings.

As halogen bonding is a weak, transient interaction, its description in solution is challenging. We demonstrate that scalar coupling constants (J) are modulated by halogen bonding. The binding-induced magnitude change of one-bond couplings, even up to five bonds from the interaction site, correlates to the interaction strength. We demonstrate this using the NMR data of 42 halogen-bonded complexes in dichloromethane solution and by quantum chemical calculations. Our observation puts scalar couplings into the toolbox of methods for characterization of halogen bond complexes in solution and paves the way for their applicability for other types of weak σ-hole interactions.

Application of multiplet structure deconvolution to extract scalar coupling constants from 1D nuclear magnetic resonance spectra.

Multiplet structure deconvolution provides a robust method to determine the values of the coupling constants in first-order 1D nuclear magnetic resonance (NMR) spectra. Functions simplifying the coupling structure for partners with spin larger than and for doublets with unequal amplitudes were introduced. The chemical shifts of the coupling partners causing mild second-order effects can, in favourable cases, be calculated from the slopes measured in doublet structures. Illustrations demonstrate that deconvolution can straightforwardly analyse multiplet posing difficulties to humans and, in some cases, extract coupling constants from unresolved multiplets.

Revealing the Surface Structure of CdSe Nanocrystals by Dynamic Nuclear Polarization-Enhanced 77Se and 113Cd Solid-State NMR Spectroscopy.

Dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) spectroscopy was used to obtain detailed surface structures of zinc blende CdSe nanocrystals (NCs) with plate or spheroidal morphologies which are capped by carboxylic acid ligands. 1D 113Cd and 77Se cross-polarization magic angle spinning (CPMAS) NMR spectra revealed distinct signals from Cd and Se atoms on the surface of the NCs, and those residing in bulk-like environments, below the surface. 113Cd cross-polarization magic-angle-turning (CP-MAT) experiments identified CdSe3O, CdSe2O2, and CdSeO3 Cd coordination environments on the surface of the NCs, where the oxygen atoms are presumably from coordinated carboxylate ligands. The sensitivity gain from DNP enabled natural isotopic abundance 2D homonuclear 113Cd-113Cd and 77Se-77Se and heteronuclear 113Cd-77Se scalar correlation solid-state NMR experiments which revealed the connectivity of the Cd and Se atoms. Importantly, 77Se{113Cd} scalar heteronuclear multiple quantum coherence (J-HMQC) experiments were used to selectively measure one-bond 77Se-113Cd scalar coupling constants (1J(77Se, 113Cd)). With knowledge of 1J(77Se, 113Cd), heteronuclear 77Se{113Cd} spin echo (J-resolved) NMR experiments were used to determine the number of Cd atoms bonded to Se atoms and vice versa. The J-resolved experiments directly confirmed that major Cd and Se surface species have CdSe2O2 and SeCd4 stoichiometries, respectively. Considering the crystal structure of zinc blende CdSe and the similarity of the solid-state NMR data for the platelets and spheroids, we conclude that the surface of the spheroidal CdSe NCs is primarily composed of {100} facets. The methods outlined here will generally be applicable to obtain detailed surface structures of various main group semiconductor nanoparticles.

Flavor-dependent U(3) Nambu–Jona-Lasinio coupling constant

A non-perturbative one gluon exchange quark-antiquark interaction is considered to compute flavor dependent U(3) Nambu-Jona-Lasinio (NJL)-type interaction of the form $G_{ij, \Gamma} (\bar{\psi} \lambda_i \Gamma \psi ) ( \bar{\psi} \lambda_j \Gamma \psi)$ for $i,j=0...8$ and $\Gamma=I, i \gamma_5$ from one loop polarization process with non degenerate u-d-s quark effective masses. The resulting NJL-type coupling constants in all channels are resolved in the long-wavelength limit and numerical results are presented for different choices of an effective gluon propagator. Leading deviations with respect to a flavor symmetric coupling constant are found to be of the order of $(M_{f_2}^*-M_{f_1}^*)^n/(M_{f_2}^*+M_{f_1}^*)^n$, for $n=1,2$, where $M_{f_i}^*$ are the effective masses of quarks $f_1,f_2=u, d$ and $s$. The scalar channel coupling constants $G_{ij, s}$ can be considerably smaller than pseudoscalar ones. The effect of the flavor-dependence of coupling constants for the masses of pions and kaons may be nearly of the same order of magnitude as the effect of the u,d and s quark mass non-degeneracy. The effect of these coupling constants is also verified for some of the light scalar mesons masses, usually described by quark-antiquark states, and for some observables of the pseudoscalar mesons.