Scalar Coupling Constants Research Articles

Investigation of the Dynamic Solution Behavior of Chloro(diene)rhodium(I) Phosphine Complexes with a Pendant Unsaturated Heterocycle at Phosphorus (2-pyridyl, 2-imidazyl; diene = COD, NBD)

Reaction of chloro(diene)rhodium(I) dimer with 2-pyridyl- and 2-imidazylphosphines resulted in the formation of the four-coordinate, square-planar complexes chloro(diene)rhodium-κ1-P-phosphine [diene = 1,5-cyclooctadiene (COD), bicyclo[2.2.1]hepta-2,5-diene (NBD)]. The nitrogen in the β-position to phosphorus provoked a fast exchange of the olefin sites in solution. Influences on this system were investigated through variation of the substituents on the phosphorus, the diene, the metal, and the heterocycle and the substitution pattern of the heterocycle. Additional isotopic labeling experiments were performed with a deuterium (1-d1) or a trideuteromethyl group (1-Me-d3) in the ortho-position to nitrogen in 1 and one deuterium in each of the olefinic positions of COD (1-COD-d2). These findings resulted in an inverse kinetic isotope effect (KIE) in the case of 1-Me-d3 and 1-COD-d2. No KIE was found by complete line-shape analysis when the pyridyl-nitrogen was labeled with 15N. The temperature dependence of T1 relaxation times for the para-proton in the pyridyl moiety was found to be a diagnostic criterion for an interaction of the pyridyl moiety with the rest of the complex, allowing the estimate of the strength of the attractive part of this interaction. No ground-state experimental proof (X-ray structure, scalar coupling constants in NMR spectroscopy) was found for this kind of interaction. DFT calculations support the nonexistence of ground-state complexes with Rh-coordinated pyridyl-nitrogen. Calculations on the pathway of the dynamic behavior in comparison to the experimental results exclude an interaction of the pyridyl-nitrogen with the COD double bonds and speak in favor of a temporary coordination of the pyridyl nitrogen to the metal center in a transition state. The calculated and measured kinetic data (including the KIEs) are in good agreement with this mechanism.

NMR Scalar Coupling Constant Reveals That Intraprotein Hydrogen Bonds Are Dynamically Stabilized by Electronic Polarization

Molecular dynamics simulations based on the standard nonpolarizable AMBER force field and on quantum-derived polarized protein-specific charge (PPC) are performed to compute NMR scalar coupling constants across hydrogen bonds for three benchmark protein systems: ubiquitin, the GB1 domain of protein G, and the SMN Tudor domain. Direct comparison of the simulation result with experimental data gives strong evidence that intraprotein hydrogen bonds are significantly stabilized by electronic polarization, both in terms of NMR scalar coupling constants and X-ray determined geometries of hydrogen bonds. Without the polarization effect in the force field, hydrogen bonds are found to be "too loose", which leads to less stable or even unstable local structures of proteins.

Computational study to assign structure, tautomerism, E/ Z and s- cis/ s- trans isomerism, π-delocalization, partial aromaticity, and the ring size of 1,3-thiazolidin-4-ones and 1,3-thiazin-4-ones formed from thiosemicarbazides

A set of structures encompassing 1-(9-acridinyl)thiosemicarbazide and its 2-methyl derivative together with their various tautomeric structures; the 5-membered ring 1,3-thiazolidin-4-one products resulting from the reaction of 1-(9-acridinyl)thiosemicarbazide and its 2-methyl derivative with dimethyl acetylenedicarboxylate (DMAD) together with the alternative 6-membered ring isomeric reaction products as well as other potential isomeric structures; and the 6-membered ring 1,3-thiazin-4-one product resulting from the reaction of 2-methyl-1-(9-acridinyl)thiosemicarbazide with methyl propiolate (MP) together with the alternative 5-membered ring isomeric reaction product were all extensively studied by molecular modeling calculations using DFT at the B3LYP/6-31G(d,p) level of theory. The ring-chain tautomerism of the thiosemicarbazides, the regio- and stereoselectivity of the reactions, the adopted conformations and E/ Z configurations of the products, the prototropic tautomerism of all the compounds, and the reasons for the predominance of the s- cis conformation of the Z configuration of the 1,3-thiazolidin-4-one product in particular were all extensively analyzed. Comparison of the modeled structures were also made to the 1,3-thiazolidin-4-one and 1,3-thiazin-4-one structures of the methyl derivative as well as 1-(9-acridinyl)thiosemicarbazide available from X-ray crystallographic analysis. Tactics utilizing spectroscopic methods {IR frequencies ( ν) and NMR chemical shifts ( δ), scalar coupling constants ( J), and NOEs ( η)} in conjunction with molecular modeling calculations of the spectral parameters {frequency calculations ( ν) and NMR δ using the GIAO method and J by calculation of the Fermi contact term} were evaluated in terms of proving 5- or 6-membered ring formation.

An experiment to measure the bound-β- decay of the free neutron

The two-body neutron β-decay into a hydrogen atom and an electron antineutrino is investigated. The hyperfine-state population of the monoenergetic hydrogen atoms (326.5 eV) yields the neutrino left-handedness or a possible right-handed admixture and possible small scalar and tensor contributions to the weak force. The constraints on the neutrino helicity and the scalar and tensor coupling constants of weak interaction can be improved considerably.

Residual dipolar coupling investigation of a heparin tetrasaccharide confirms the limited effect of flexibility of the iduronic acid on the molecular shape of heparin

The solution conformation of a fully sulfated heparin-derived tetrasaccharide, I, was studied in the presence of a 4-fold excess of Ca2+. Proton–proton and proton–carbon residual dipolar couplings (RDCs) were measured in a neutral aligning medium. The order parameters of two rigid hexosamine rings of I were determined separately using singular value decomposition and ab initio structures of disaccharide fragments of I. The order parameters were very similar implying that a common order tensor can be used to analyze the structure of I. Using one order tensor, RDCs of both hexosamine rings were used as restraints in molecular dynamics simulations. RDCs of the inner iduronic acid were calculated for every point of the molecular dynamics trajectory. The fitting of the calculated RDCs of the two forms of the iduronic acid to the experimental values yielded a population of 1C4 and 2So conformers of iduronic acid that agreed well with the analysis based on proton–proton scalar coupling constants. The glycosidic linkage torsion angles in RDC-restrained molecular dynamics (MD) structures of I are consistent with the interglycosidic three-bond proton–carbon coupling constants. These structures also show that the shape of heparin is not affected dramatically by the conformational flexibility of the iduronic acid ring. This is in line with conclusions of previous studies based on MD simulations and the analysis of 1H-1H NOEs. Our work therefore demonstrates the effectiveness of RDCs in the conformational analysis of glycosaminoglycans.

Evaluating the Performance of the ff99SB Force Field Based on NMR Scalar Coupling Data

Force-field validation is essential for the identification of weaknesses in current models and the development of more accurate models of biomolecules. NMR coupling and relaxation methods have been used to effectively diagnose the strengths and weaknesses of many existing force fields. Studies using the ff99SB force field have shown excellent agreement between experimental and calculated order parameters and residual dipolar calculations. However, recent studies have suggested that ff99SB demonstrates poor agreement with J-coupling constants for short polyalanines. We performed extensive replica-exchange molecular-dynamics simulations on Ala3 and Ala5 in TIP3P and TIP4P-Ew solvent models. Our results suggest that the performance of ff99SB is among the best of currently available models. In addition, scalar coupling constants derived from simulations in the TIP4P-Ew model show a slight improvement over those obtained using the TIP3P model. Despite the overall excellent agreement, the data suggest areas for possible improvement.

15N−1H Scalar Coupling Perturbation: An Additional Probe for Measuring Structural Changes Due to Ligand Binding

Chemical shift perturbation mapping of backbone amides is one of the most widely employed techniques in biomolecular NMR, providing residue-by-residue information on interaction interfaces, ligand binding, and chemical modification sites, even for samples where poor solubility, short lifetime, or large size precludes more sophisticated experimental approaches. Significant changes can also occur in the amide one-bond (15)N-(1)H scalar coupling constants for glutamine binding protein (GlnBP) due to ligand binding. Like chemical shift perturbations, large changes (>1 Hz) are seen near the site of glutamine binding, though perturbations also occur distant to the site. The coupling constant perturbations correlate with significant structural changes, especially changes in backbone hydrogen bonding. Thus, amide scalar coupling perturbation can serve as an adjunct to chemical shift perturbation, providing additional information on both short-range and longer-range, allosteric structural changes.

Structural Interpretation of J Coupling Constants in Guanosine and Deoxyguanosine: Modeling the Effects of Sugar Pucker, Backbone Conformation, and Base Pairing

The (3)J(C8-H1'), (3)J(C4-H1'), (1)J(C8-H8), (1)J(C1'-H1'), (1)J(C2'-H2'), and (1)J(C2'-H2'2) indirect scalar coupling constants were calculated with the density functional theory in the deoxyguanosine and riboguanosine molecules. The following geometry descriptors were considered in analysis of the structural dependence of the six J couplings: the glycosidic torsion angle chi and conformation of the hydroxymethyl group at the C4' carbon of sugar mimicking the backbone residue and the sugar pucker (C2'-, C3'-endo). The (3)J(C8-H1') and (3)J(C4-H1') couplings, which are typically assigned to the chi torsion, also depended on the sugar pucker, although the calculated dependence of the latter coupling on sugar pucker was nearly negligible. New parametrization of the Karplus equations, taking into account the stereoinversion effect at the glycosidic nitrogen atom and solvent effects, was calculated for the (3)J(C8-H1') and (3)J(C4-H1') coupling assigned to the chi torsion. The calculated phase shift of chi torsion angle in these new Karplus equations was larger by approximately 10 degrees compared to its commonly accepted value of 60 degrees (Wijmenga, S. S.; van Buuren, B. N. M. Prog. NMR Spectrosc. 1998, 32, 287.). The calculated (1)J(C2'-H2') and (1)J(C2'-H2'2) coupling dominantly depended on the sugar type (deoxyribose or ribose) and its pucker, while the (1)J(C1'-H1') and (1)J(C8-H8) coupling dominantly depended on the glycosidic torsion angle, although quantitatively, all four (1)J couplings depended on both geometry parameters. The dependences of j-couplings on the torsion angle chi calculated in isolated nucleosides were compared with those taking into account the effect of base pairing occurring in the WC/SE RNA base pair family, which appeared to be minor. The calculated (3)J couplings agreed well with available experimental data similarly as the (1)J couplings, although lack of experimental data diminished more reliable validation of the later couplings.

Dirac Born Infeld (DBI) cosmic strings

Motivated by brane physics, we consider the non-linear Dirac-Born-Infeld (DBI) extension of the Abelian-Higgs model and study the corresponding cosmic string configurations. The model is defined by a potential term, assumed to be of the mexican hat form, and a DBI action for the kinetic terms. We show that it is a continuous deformation of the Abelian-Higgs model, with a single deformation DBI parameter depending on a dimensionless combination of the scalar coupling constant, the vacuum expectation value of the scalar field at infinity, and the brane tension. By means of numerical calculations, we investigate the profiles of the corresponding DBI-cosmic strings and prove that they have a core which is narrower than that of Abelian-Higgs strings. We also show that the corresponding action is smaller than in the standard case suggesting that their formation could be favoured in brane models. Moreover we show that the DBI-cosmic string solutions are non-pathological everywhere in parameter space. Finally, in the limit in which the DBI model reduces to the Bogomolnyi-Prasad-Sommerfield (BPS) Abelian-Higgs model, we find that DBI cosmic strings are no longer BPS: rather they have positive binding energy. We thus argue that, when they meet, two DBI strings will not bind with the corresponding formation of a junction, and hence that a network of DBI strings is likely to behave as a network of standard cosmic strings. On the other hand, we also find that, if the BPS condition is no longer satisfied and the coupling constant is less than twice the charge squared of the scalar field, DBI strings can change their behaviour from type I to type II depending on the DBI parameter.

Distribution of Conformations Sampled by the Central Amino Acid Residue in Tripeptides Inferred From Amide I Band Profiles and NMR Scalar Coupling Constants

The conformational preference of individual amino acid residues in the unfolded state of peptides and proteins is the subject of a continuous debate. Research has mostly been focused on alanine, owing to its abundance in proteins and its relevance for the understanding of helix <----> coil transitions. In the current study, we have analyzed the amide I band profiles of the IR, isotropic and anisotropic Raman, and VCD profiles of trialanine in terms of a conformational model which, for the first time, explicitly considers the entire ensemble of possible conformations rather than representative structures. The distribution function utilized for a satisfactory simulation of the amide I band profiles was found to also reproduce a set of five J coupling constants reported by Graf et al. (Graf, J.; et al. J. Am. Chem. Soc. 2007, 129, 1179). The results of our analysis reveal a PPII fraction of approximately 0.84 for the central alanine residue, which strongly corroborates the notion that alanine has a very high PPII propensity, exceeding the values obtained from restricted coil libraries. We performed a similar analysis for trivaline and found that the dominant fraction of its central residue is a beta-strand. The fraction of the respective distribution is 0.68. The remaining fraction contains contributions from helical and PPII conformations. The results of our analysis enable us to decide on the suitability of force fields used for MD simulations of short alanine-containing peptides. The paper establishes vibrational spectroscopy as a suitable method to explore the energy landscape of amino acid residues.

Distribution of Conformations Sampled by the Central Amino Acid Residue in GXG Peptides Inferred from Amide 1′ Band Profiles and NMR Scalar Coupling Constants

The conformational propensity of amino acids in the unfolded state of peptides and proteins is the subject of ongoing deliberation. Recent research has mostly focused on alanine, owing to its abundance in proteins and its relevance for the understanding of helix coil transitions. We have analyzed the amide I' band profiles of the IR, isotropic and anisotropic Raman, and VCD profiles of a series of GXG peptides, X representing a subset of the naturally occurring amino acids, in terms of a conformational model which explicitly considers the entire ensemble of possible conformations rather than representative structures. The distribution function utilized for satisfactory simulations of the amide I' band profiles was found to also reproduce a set of seven J-coupling constants reported by Graf et al1. The results of our analysis reveal a PPII fraction of 0.91 for the central alanine residue in GAG, which strongly corroborates the notion that alanine has a very high PPII propensity. We performed a similar analysis for X=E, F, S, V, K, L and M. Preliminary indication is that E, F, K and L exhibit a substantial PPII propensity, whereas S, V and M exhibit a less pronounced PPII propensity with an increased propensity for β-strand. We also used distributions from coil libraries and MD simulations to model amide I band profiles and J-coupling constants for alanine and valine. We found most of them to be inconsistent with our experimental data. Thus, these results clearly demonstrate that caution must be taken in using coil libraries and MD simulations to describe the unfolded state of peptides and proteins, and that experimental data are a prerequisite for quantitative evaluation of amino acid residues.

Structure and Dynamics of the ApA, ApC, CpA, and CpC RNA Dinucleoside Monophosphates Resolved with NMR Scalar Spin−Spin Couplings

The measured NMR scalar coupling constants (J-couplings) in the XpY, (X,Y = adenine (A) or cytosine (C)) RNA dinucleoside monophosphates (DMPs) were assigned to the backbone (alpha, beta, gamma, delta, epsilon, zeta) and glycosidic (chi) torsion angles in order to resolve the global structure of the DMP molecules. The experimental J-couplings were correlated with the theoretical J-couplings obtained as the dynamical averages of the Karplus equations relevant to the torsion angles. The dynamical information was captured using the molecular dynamics (MD) calculation method. The individual conformational flexibility of the four DMP molecules was thus consistently probed with the NMR J-couplings. The calculated structure and flexibility of the DMP molecules depend on the sequence considered with respect to the 5' and 3' end of the DMP molecules (5'-XpY-3'). The dynamical characteristics of the two nucleosides are not equivalent even for the ApA and CpC homologues. An enhancement of the sampling in the MD calculations was achieved using five different starting structural motives classified previously for the RNA backbone in the solid phase (Richardson et al. RNA 2008, 14, 465-481). The initial structures were selected on the basis of a database search for RNA oligonucleotides. Frequent interconversions between the conformers during the MD calculations were actually observed. The structural interpretation of the NMR spectroscopic data based on the MD simulations combined with the Karplus equations indicates that the dominant conformation of the DMP molecules in solution corresponds to the A-RNA form. For 52% of the total simulation time (1000 ns), the zeta(g-)-alpha(g-)-gamma(g+) backbone topology corresponding to the canonical A-RNA form was observed, with roughly equally populated C2'- and C3'-endo sugar puckers interconverting on the nanosecond time scale. However, other noncanonical patterns were also found and thus indicate their relatively high potential to be populated in the dynamical regime. For approximately 72% of the time portion when the A-RNA of the zeta-alpha-gamma combination occurred, the nucleobases were classified as being mutually stacked. The geometries of the nucleobases classified in this work as stacked were significantly more populated for the DMP molecules with adenosine at the 3' end (ApA and CpA DMPs) than the ApC or CpC RNA molecules with C at the 3' end.

Hyperfine energy levels of alkali-metal dimers: Ground-state homonuclear molecules in magnetic fields

We investigate the hyperfine energy levels and Zeeman splittings for homonuclear alkali-metal dimers in low-lying rotational and vibrational states, which are important for experiments designed to produce quantum gases of deeply bound molecules. We carry out density-functional theory (DFT) calculations of the nuclear hyperfine coupling constants. For nonrotating states, the zero-field splittings are determined almost entirely by the scalar nuclear spin-spin coupling constant. By contrast with the heteronuclear case, the total nuclear spin remains a good quantum number in a magnetic field. We also investigate levels with rotational quantum number N = 1, which have long-range anisotropic quadrupole-quadrupole interactions and may be collisionally stable. For these states the splitting is dominated by nuclear quadrupole coupling for most of the alkali-metal dimers and the Zeeman splittings are considerably more complicated.

Probing local structures of siliceous zeolite frameworks by solid-state NMR and first-principles calculations of 29Si–O–29Si scalar couplings

Subtle structural details of siliceous zeolites are probed by using two-bond scalar (J) coupling constants to characterize covalently bonded 29Si-O-29Si site pairs and local framework order. Solid-state two-dimensional (2D) 29Si{29Si} NMR measurements and first-principles calculations of 2J(29Si-O-29Si) couplings shed insights on both the local structures of siliceous zeolites Sigma-2 and ZSM-12, as well as the sensitivity of J couplings for detailed characterization analyses. DFT calculations on a model linear silicate dimer show that 2J(Si-O-Si) couplings have complicated multiple angular dependencies that make semi-empirical treatments impractical, but which are amenable to cluster approaches for accurate J-coupling calculations in zeolites. DFT calculations of 2J(29Si-O-29Si) couplings of the siliceous zeolite Sigma-2, whose framework structure is known to high accuracy from single-crystal X-ray diffraction studies, yield excellent agreement between calculated and experimentally measured 2J(Si-O-Si) couplings. For the siliceous zeolite ZSM-12, calculated 2J(29Si-O-29Si) couplings based on less-certain powder X-ray diffraction analyses deviate significantly from experimental values, while a refined structure based on 29Si chemical-shift-tensor analyses shows substantially improved agreement. 29Si J-coupling interactions can be used as sensitive probes of local structures of zeolitic frameworks and offer new opportunities for refining and solving complicated structures, in combination with complementary scattering, modeling, and other nuclear spin interactions.

Chirality-dependent macroscopic force between chiral molecules and achiral matter

A non-zero macroscopic chirality-dependent force between achiral matter and homochiral molecules due to the exchange of light particles is shown theoretically. It has the opposite sign for molecules with opposite chirality. As an example, this force between a copper block and a vessel of chiral molecules (methyl phenyl carbinol nitrite) is calculated in the crystal field theory. The magnitude of the force is estimated with the published limits of scalar and pseudo-scalar coupling constants. Its possible influence to the gravitational experiments testing the equivalence principle is discussed as well.

A Chiral Macroscopic Force between Liquid of Butyl Alcohol and Copper Block

A non-zero macroscopic chirality-dependent force between a copper block and a vessel of homochiral molecules (butyl alcohol) is calculated quantitatively with the central field approximation. The magnitude of the force is estimated with the published limits of the scalar and pseudo-scalar coupling constants.

Direct Comparison of Experimental and Calculated NMR Scalar Coupling Constants for Force Field Validation and Adaptation.

The ability to measure scalar coupling constants across hydrogen bonds ((3h)JNC') from high-resolution NMR experiments allows the characterization of detailed structural properties of biomolecules. To analyze those, a parametrized model based on the linear combination of atomic orbitals relates H-bond geometries with the measured (3h)JNC' coupling magnitude. In the present study the dependence of calculated (3h)JNC' coupling constants on force field parameters is assessed. It is shown that increased polarity of the hydrogen bond improves the calculated (3h)JNC' coupling constants and shifts the conformational ensemble sampled from the molecular dynamics (MD) simulations toward the experimentally measured one. Increased charges lead to more narrow distance and angle distributions and improve the agreement between calculated and measured (3h)JNC' couplings. However, different secondary structures are better represented by different magnitudes of electrostatic interactions-different atomic partial charges in the present work-as indicated by root-mean square deviations (rsmds) between observed and calculated coupling constants (3h)JNC'. The parametrization of the empirical formula is found to be meaningful and robust, but the parameter values are not universal across different proteins and different secondary structural elements (α-helices, β-sheets and loops). Using standard and slightly increased CHARMM charges, predictions for the as-yet unknown scalar coupling constants for the V54A and I6A mutants of protein G are made.

A user-friendly Matlab program and GUI for the pseudorotation analysis of saturated five-membered ring systems based on scalar coupling constants

BackgroundThe advent of combinatorial chemistry has revived the interest in five-membered heterocyclic rings as scaffolds in pharmaceutical research. They are also the target of modifications in nucleic acid chemistry. Hence, the characterization of their conformational features is of considerable interest. This can be accomplished from the analysis of the 3JHH scalar coupling constants.ResultsA freely available program including an easy-to-use graphical user interface (GUI) has been developed for the calculation of five-membered ring conformations from scalar coupling constant data. A variety of operational modes and parameterizations can be selected by the user, and the coupling constants and electronegativity parameters can be defined interactively. Furthermore, the possibility of generating high-quality graphical output of the conformational space accessible to the molecule under study facilitates the interpretation of the results. These features are illustrated via the conformational analysis of two 4'-thio-2'-deoxynucleoside analogs. Results are discussed and compared with those obtained using the original PSEUROT program.ConclusionA user-friendly Matlab interface has been developed and tested. This should considerably improve the accessibility of this kind of calculations to the chemical community.

Structural characterization by Nuclear Magnetic Resonance of ozonized triolein

In the present study ozonized triolein with 739 mmolequiv/ kg peroxide index is characterized by NMR.The triolein and ozonized triolein show very similar 1H NMR spectra except for the resonances at δ 9.74 ppm, which correspond to aldehydic protons and δ 5.14 ppm (ozonides methylic protons). Other new signal assignments are based on the connectivities provided by the proton scalar coupling constants δ 2.41 ppm (methylenic group allylic to aldehydic protons and ozonides methynic protons) and δ 1.67 ppm (methylenic protons in position with respect to ozonides methylic protons). From the 13 C and 1 H- 13 C spectrum of the ozonized triolein, the presence of ozonides was confirmed by the signals δ 104.2 and 104.3 ppm, respectively. Other new signals in δ 43.9 ppm confirm the presence of methylenic carbon ozonides. From the structural elucidation of ozonated triglycerides, relevant chemical information about ozonated vegetable oil can be found .

High-resolution 19F and 1H NMR of a vinylidenefluoride telomer

The reaction products of vinylidenefluoride (VDF) with methanol as a telogen have been analysed in the solution state by 1H and 19F nuclear magnetic resonance (NMR) spectroscopy. High-resolution 19F and 1H NMR spectra were achieved using high-power 1H and 19F decoupling, respectively, giving superior resolution and revealing previously unresolved signals of the vinylidenefluoride telomer (VDFT). 1H and 19F homo- and hetero-nuclear scalar coupling constants are presented and the spectra of functional groups and reverse units (including the identification of short-chain structures) are discussed. Furthermore, the application of 19F or 1H decoupling for the correct assessment of reverse-unit content and degree of polymerisation is demonstrated. This work highlights the need for high-resolution NMR spectroscopy to determine both the chemical structure and the composition of these important fluoropolymers.