Proton Chemical Shifts Research Articles

Data of 1H/13C NMR spectra and degree of substitution for chitosan alkyl urea.

The data shown in this article are related to the subject of an article in Carbohydrate Polymers, entitled “Synthesis and characterization of chitosan alkyl urea” [1]. 1H NMR and 13C NMR spectra of chitosan n-octyl urea, chitosan n-dodecyl urea and chitosan cyclohexyl urea are displayed. The chemical shifts of proton and carbon of glucose skeleton in these chitosan derivatives are designated in detail. Besides, 1H NMR spectra of chitosan cyclopropyl urea, chitosan tert-butyl urea, chitosan phenyl urea and chitosan N,N-diethyl urea and the estimation of the degree of substitution are also presented. The corresponding explanations can be found in the above-mentioned article.

Thiol–thione tautomeric analysis, spectroscopic (FT-IR, Laser-Raman, NMR and UV–vis) properties and DFT computations of 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiol molecule

In this study, the 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiol molecule (C7H6N4S) molecule has been characterized by using FT-IR, Laser-Raman, NMR and UV–vis spectroscopies. Quantum chemical calculations have been performed to investigate the molecular structure (thione–thiol tautomerism), vibrational wavenumbers, electronic transition absorption wavelengths in DMSO solvent and vacuum, proton and carbon-13 NMR chemical shifts and HOMOs-LUMOs energies at DFT/B3LYP/6-311++G(d,p) level for all five tautomers of the title molecule. The obtained results show that the calculated vibrational wavenumbers, NMR chemical shifts and UV–vis wavelengths are in a good agreement with experimental data.

1H NMR and computational studies of the conformations in solution of one host/guest complex formed with an usnic acid tweezer and 2,4,7-trinitro-9-fluorenone (TNF)

In a host-guest model formed by a molecular tweezer 4, bearing two usnic acid units, and TNF, the TNF protons chemical shifts are measured at various temperatures. With the help of a computational study, the geometries of complexation of this host-guest system are identified and their TNF protons chemical shifts calculated. Data analysis led to conclude that in solution two types of conformations are present: the ‘lateral’ one (similar to the structure found in the solid state) and the ‘longitudinal’ one in which the TNF is less engaged inside the host. The proportion of the latter increases with decreasing temperatures.

1H NMR Spectroscopy of Dopamine Interacting with Lipid Vesicles

Dopamine, a naturally occurring neurotransmitter, plays an important role in the brain's reward system, and acts on sensory receptors in the brain. Neurotransmitters are contained in lipid membraned vesicles, and are released by exocytosis. All neurotransmitters interact with transport and receptor proteins in glial cells, on neuronal dendrites, and at the axonal button, and also must interact with membrane lipids. However, the extent of direct interaction between lipid membranes in the absence of receptors and transport proteins has not been extensively investigated. A recently developed NMR method uses an equivalent isopropanol concentration (EIC) scale to describe the interaction of aromatic moieties with lipid membranes as demonstrated for aromatic side chains of amino acid residues [1]. In this method, a range of isopropanol concentrations is used to provide a reference scale for hydrophobic interactions. Therefore, similar UV and NMR measurements were made with dopamine dissolved into varying concentrations of isopropanol to establish a standard EIC curve for measurement of dopamine interactions with lipid membranes. UV spectroscopy shows a maximum absorbance range around 286.6 - 288.2 nm and 1H NMR spectroscopy shows a progressive shift of aromatic ring proton chemical shifts towards higher field as the concentration of isopropanol increases. Next, dopamine was mixed with sonicated unilamellar DOPS vesicles and with sonicated unilamellar DOPC vesicles to measure its affinity and orientation in each type of vesicles. The measured EIC maps show that dopamine interacts differently with PC and PS lipids consistent with the fact that the positively charged dopamine experiences an electrostatic attraction for negatively charged PS lipids. This suggests that the extent of dopamine release could depend on lipid composition. [1] Johnson et al., Journal of Membrane Biology, 248, 695-703, 2015.

Structure, NMR and Electronic Spectra of [m.n]Paracyclophanes with Varying Bridges Lengths (m, n = 2-4).

Extending our earlier studies on cyclophanes, we here report the structure, chemical shifts, spin-spin coupling constants, absorption and emission properties of [m.n]paracyclophanes, m, n = 2-4, obtained using a combination of experimental and computational techniques. Accurate values of proton chemical shifts as well as of JHH for the bridges are determined. The experimental chemical shifts, coupling constants, absorption and emission wavelengths are satisfactorily reproduced using density functional theory calculations, using both the B3LYP and ωB97X-D functionals. The geometries predicted using a functional that includes dispersion corrections (ωB97X-D) are in a better agreement with available experimental values than those obtained using the B3LYP method. Up to 8 UV-vis absorption/emission bands have been observed (or anticipated in the region below 200 nm) and assigned on the basis of quantum-chemical calculations. Optimized excited-state geometries showed that the distances between the aromatic bridgehead carbon atoms of all the [m.n]paracyclophanes in the excited state decrease compared to the ground-state geometries by ca. 0.2-0.9 Å, the largest being for [4.4]paracyclophane, though the rather large differences in the calculated emission wavelength compared to experiment cast some doubts on the accuracy of the excited-state geometries.

Constant-time 2D and 3D through-bond correlation NMR spectroscopy of solids under 60 kHz MAS.

Establishing connectivity and proximity of nuclei is an important step in elucidating the structure and dynamics of molecules in solids using magic angle spinning (MAS) NMR spectroscopy. Although recent studies have successfully demonstrated the feasibility of proton-detected multidimensional solid-state NMR experiments under ultrafast-MAS frequencies and obtaining high-resolution spectral lines of protons, assignment of proton resonances is a major challenge. In this study, we first re-visit and demonstrate the feasibility of 2D constant-time uniform-sign cross-peak correlation (CTUC-COSY) NMR experiment on rigid solids under ultrafast-MAS conditions, where the sensitivity of the experiment is enhanced by the reduced spin-spin relaxation rate and the use of low radio-frequency power for heteronuclear decoupling during the evolution intervals of the pulse sequence. In addition, we experimentally demonstrate the performance of a proton-detected pulse sequence to obtain a 3D (1)H/(13)C/(1)H chemical shift correlation spectrum by incorporating an additional cross-polarization period in the CTUC-COSY pulse sequence to enable proton chemical shift evolution and proton detection in the incrementable t1 and t3 periods, respectively. In addition to through-space and through-bond (13)C/(1)H and (13)C/(13)C chemical shift correlations, the 3D (1)H/(13)C/(1)H experiment also provides a COSY-type (1)H/(1)H chemical shift correlation spectrum, where only the chemical shifts of those protons, which are bonded to two neighboring carbons, are correlated. By extracting 2D F1/F3 slices ((1)H/(1)H chemical shift correlation spectrum) at different (13)C chemical shift frequencies from the 3D (1)H/(13)C/(1)H spectrum, resonances of proton atoms located close to a specific carbon atom can be identified. Overall, the through-bond and through-space homonuclear/heteronuclear proximities determined from the 3D (1)H/(13)C/(1)H experiment would be useful to study the structure and dynamics of a variety of chemical and biological solids.

Synthesis and Characterization of Some Crown Ether Complexes of Tl(I) Ion

The affinity of crown ethers for metal ion is strongly dependent on the size of the ring of the crown ether. The crown ether-metal ion binding is enhanced in the absence of non-coplanar donor oxygen atoms and electron withdrawing substituents in the crown ether skeleton. The study of absorption of radio frequency radiation by a magnetic nucleus provides useful information regarding structure of a number of organic and inorganic compounds. Small changes were observed in the chemical shift of 1-H in 15C5, 18C6 and, 1-H as well as 2-H, in dibenzo18C6. After formation of the [Metal-Crown ether]Ligand complex, the proton chemical shift δ(−CH2-O-) shows significant downfield shifts [Δδ(−CH2-O-)= 0.08–0.25 ppm], indicating metal-ligand bond formation. The degree of downfield shift shows the relative strength of the complexes. The 1H-NMR spectrum of dibenzo18C6 shows peaks at, δ1=3.9–4.1 ppm, (16H, 8-CH2O-), δ2=6.8–7.0 ppm, (8H, aryl-CH-), in CDCl3. The shift of-CH2-signals in complexes from free crown ether unambiguously suggested the coordination of crown ether oxygen of 15C5, 18C6 as well as dibenzo18C6 with thallium ion.

Access to aliphatic protons as reporters in non-deuterated proteins by solid-state NMR.

Interactions within proteins, with their surrounding, and with other molecules are mediated mostly by hydrogen atoms. In fully protonated, inhomogeneous, or larger proteins, however, aliphatic proton shifts tend to show little dispersion despite fast Magic-Angle Spinning. 3D correlations dispersing aliphatic proton shifts by their better resolved amide N/H shifts can alleviate this problem. Using inverse second-order cross-polarization (iSOCP), we here introduce dedicated and improved means to sensitively link site-specific chemical shift information from aliphatic protons with a backbone amide resolution. Thus, even in cases where protein deuteration is impossible, this approach may enable access to various aspects of protein functions that are reported on by protons.

The local composition behavior in binary solutions of diethylamine acetate ionic liquid

In order to uncover the micro-structural heterogeneities in the solutions of ammonium-based ionic liquids, diethylamine acetate (DEAA) has been synthesized and concentration-dependent 1H NMR spectra of three binary solutions, namely DEAA/water, DEAA/DMSO and DEAA/acetone, at different compositions have been measured at 298.15K. The proton chemical shifts of DEAA have been correlated using the 1H NMR local composition (LC) model. It has been found that the self-associations of DEAA were predominant instead of DEAA–solvent interactions within DEAA-rich region. However within solvent-rich region, DEAA could mainly interact with solvent molecules, indicating that the network of DEAA has been greatly destroyed by effects of solvents. In addition, the ability of solvents to break down the structure of DEAA followed in such order: water>DMSO>acetone, which was consistent with changes of physicochemical properties of these solutions.

Aromaticity/antiaromaticity of phospha-analogues of carbocyclic ions: A DFT investigation

The aromaticity or antiaromaticity of mono- and polyphospha analogues of carbocyclic cations and anions, namely cyclopropenium, cyclopropenide, cyclopentadienium and cyclopentadienide ions has been investigated at the DFT (B3LYP/6-31+G∗) level on the basis of bond lengths equalization, aromatic stabilization energies, proton chemical shifts, NICS(0), NICS(1) and NICS(1)zz tensor component values and magnetic susceptibility exaltation criteria. The results reveal that the aromaticity is sustained on one or more CH/P exchange(s) in cyclopropenium and cyclopentadienide ions. However, as regards the antiaromatic systems, the results are not uniform. Furthermore, of all the criteria investigated, only magnetic susceptibility exaltation results are consistent, which have negative values for the aromatic systems and positive values for the antiaromatic ions.

EWGWS insert in Plasmodium falciparum ookinete surface enolase is involved in binding of PWWP containing peptides: Implications to mosquito midgut invasion by the parasite

There are multiple stages in the life cycle of Plasmodium that invade host cells. Molecular machinery involved is such host–pathogen interactions constitute excellent drug targets and/or vaccine candidates. A screen using a phage display library has previously demonstrated presence of enolase on the surface of the Plasmodium ookinete. Phage-displayed peptides that bound to the ookinete contained a conserved motif (PWWP) in their sequence. Here, direct binding of these peptides with recombinant Plasmodium falciparum enolase (rPfeno) was investigated. These peptides showed specific binding to rPfeno, but failed to bind to other enolases. Plasmodium spp enolases are distinct in having an insert of five amino acids (104EWGWS108) that is not found in host enolases. The possibility of this insert being the recognition motif for the PWWP containing peptides was examined, (i) by comparing the binding of the peptides with rPfeno and a deletion variant Δ-rPfeno lacking 104EWGWS108, (ii) by measuring the changes in proton chemical shifts of PWWP peptides on binding to different enolases and (iii) by inter-molecular docking experiment to locate the peptide binding site. Results from these studies showed that the pentapeptide insert of Pfeno indeed constitutes the binding site for the PWWP domain containing peptide ligands. Search for sequences homologous to phage displayed peptides among peritrophic matrix proteins resulted in identification of perlecan, laminin, peritrophin and spacran. The possibility of these PWWP domain-containing proteins in the peritrophic matrix of insect gut to interact with ookinete cell surface enolase and facilitate the invasion of mosquito midgut epithelium is discussed.

Nuclear Magnetic Resonance-Assisted Prediction of Secondary Structure for RNA: Incorporation of Direction-Dependent Chemical Shift Constraints.

Knowledge of RNA structure is necessary to determine structure–function relationships and to facilitate design of potential therapeutics. RNA secondary structure prediction can be improved by applying constraints from nuclear magnetic resonance (NMR) experiments to a dynamic programming algorithm. Imino proton walks from NOESY spectra reveal double-stranded regions. Chemical shifts of protons in GH1, UH3, and UH5 of GU pairs, UH3, UH5, and AH2 of AU pairs, and GH1 of GC pairs were analyzed to identify constraints for the 5′ to 3′ directionality of base pairs in helices. The 5′ to 3′ directionality constraints were incorporated into an NMR-assisted prediction of secondary structure (NAPSS-CS) program. When it was tested on 18 structures, including nine pseudoknots, the sensitivity and positive predictive value were improved relative to those of three unrestrained programs. The prediction accuracy for the pseudoknots improved the most. The program also facilitates assignment of chemical shifts to individual nucleotides, a necessary step for determining three-dimensional structure.

Solution Structural Studies of GTP:Adenosylcobinamide-Phosphateguanylyl Transferase (CobY) from Methanocaldococcus jannaschii.

GTP:adenosylcobinamide-phosphate (AdoCbi-P) guanylyl transferase (CobY) is an enzyme that transfers the GMP moiety of GTP to AdoCbi yielding AdoCbi-GDP in the late steps of the assembly of Ado-cobamides in archaea. The failure of repeated attempts to crystallize ligand-free (apo) CobY prompted us to explore its 3D structure by solution NMR spectroscopy. As reported here, the solution structure has a mixed α/β fold consisting of seven β-strands and five α-helices, which is very similar to a Rossmann fold. Titration of apo-CobY with GTP resulted in large changes in amide proton chemical shifts that indicated major structural perturbations upon complex formation. However, the CobY:GTP complex as followed by 1H-15N HSQC spectra was found to be unstable over time: GTP hydrolyzed and the protein converted slowly to a species with an NMR spectrum similar to that of apo-CobY. The variant CobYG153D, whose GTP complex was studied by X-ray crystallography, yielded NMR spectra similar to those of wild-type CobY in both its apo- state and in complex with GTP. The CobYG153D:GTP complex was also found to be unstable over time.

Synthesis and Structural Characterization of Some New Magnesium Formamidinates

Abstract[Mg(Form)2(THF)] [Form = bis(2,6‐dimethylphenyl)formamidinate (XylForm) (1), bis(2,6‐diethylphenyl)formamidinate, (EtForm) (2), bis(2,6‐diisopropylphenyl)formamidinate (DippForm) (3)] are conveniently synthesized by treating bis(2,6‐dimethylphenyl)formamidine, bis(2,6‐diethylphenyl)formamidine, or bis(2,6‐diisopropylphenyl)formamidine, respectively, with half an equivalent of dibutylmagnesium in THF. Compounds 1–3 are mononuclear species in the solid state with five coordinate central metal atoms. The 1H NMR chemical shift of the formamidinate formyl proton exhibits a correlation with ligand sterics wherein increasing bulk leads to a shift to higher field.

Proton chemical shift tensors determined by 3D ultrafast MAS double-quantum NMR spectroscopy.

Proton NMR spectroscopy in the solid state has recently attracted much attention owing to the significant enhancement in spectral resolution afforded by the remarkable advances in ultrafast magic angle spinning (MAS) capabilities. In particular, proton chemical shift anisotropy (CSA) has become an important tool for obtaining specific insights into inter/intra-molecular hydrogen bonding. However, even at the highest currently feasible spinning frequencies (110-120 kHz), (1)H MAS NMR spectra of rigid solids still suffer from poor resolution and severe peak overlap caused by the strong (1)H-(1)H homonuclear dipolar couplings and narrow (1)H chemical shift (CS) ranges, which render it difficult to determine the CSA of specific proton sites in the standard CSA/single-quantum (SQ) chemical shift correlation experiment. Herein, we propose a three-dimensional (3D) (1)H double-quantum (DQ) chemical shift/CSA/SQ chemical shift correlation experiment to extract the CS tensors of proton sites whose signals are not well resolved along the single-quantum chemical shift dimension. As extracted from the 3D spectrum, the F1/F3 (DQ/SQ) projection provides valuable information about (1)H-(1)H proximities, which might also reveal the hydrogen-bonding connectivities. In addition, the F2/F3 (CSA/SQ) correlation spectrum, which is similar to the regular 2D CSA/SQ correlation experiment, yields chemical shift anisotropic line shapes at different isotropic chemical shifts. More importantly, since the F2/F1 (CSA/DQ) spectrum correlates the CSA with the DQ signal induced by two neighboring proton sites, the CSA spectrum sliced at a specific DQ chemical shift position contains the CSA information of two neighboring spins indicated by the DQ chemical shift. If these two spins have different CS tensors, both tensors can be extracted by numerical fitting. We believe that this robust and elegant single-channel proton-based 3D experiment provides useful atomistic-level structural and dynamical information for a variety of solid systems that possess high proton density.

Computational and NMR Spectroscopic Evidence for Stereochemistry-Dependent Conformations of 2,2,6,6-Tetramethylpiperidinyl-Masked 1,2-Diols.

2,2,6,6-Tetramethylpiperidinyl-masked 1,2-diols exhibited stereochemistry-dependent hydroxyl proton chemical shifts: ca. 7 ppm for the syn diastereomer and ca. 2 ppm for the anti diastereomer. A computational search for low energy geometries revealed that the syn isomer favors a six-membered ring hydrogen bond to nitrogen and the anti isomer favors a five-membered ring hydrogen bond to oxygen. The computed low energy conformations were found to have a large difference in hydroxyl proton shielding that was reflected in the experimental chemical shift difference. This chemical shift difference was observed in a broad range of solvents, and thus may be useful as a stereochemical probe. The stereochemistry-dependent conformation and chemical shift signature appeared to be due to a syn pentane interaction between the gem-dimethyl groups on the 2,2,6,6-tetramethylpiperidinyl moiety.

Theoretical and experimental NMR studies on muscimol from fly agaric mushroom (Amanita muscaria)

In this article we report results of combined theoretical and experimental NMR studies on muscimol, the bioactive alkaloid from fly agaric mushroom (Amanita muscaria). The assignment of 1H and 13C NMR spectra of muscimol in DMSO-d6 was supported by additional two-dimensional heteronuclear correlated spectra (2D NMR) and gauge independent atomic orbital (GIAO) NMR calculations using density functional theory (DFT). The effect of solvent in theoretical calculations was included via polarized continuum model (PCM) and the hybrid three-parameter B3LYP density functional in combination with 6-311++G(3df,2pd) basis set enabled calculation of reliable structures of non-ionized (neutral) molecule and its NH and zwitterionic forms in the gas phase, chloroform, DMSO and water. GIAO NMR calculations, using equilibrium and rovibrationally averaged geometry, at B3LYP/6-31G* and B3LYP/aug-cc-pVTZ-J levels of theory provided muscimol nuclear magnetic shieldings. The theoretical proton and carbon chemical shifts were critically compared with experimental NMR spectra measured in DMSO. Our results provide useful information on its structure in solution. We believe that such data could improve the understanding of basic features of muscimol at atomistic level and provide another tool in studies related to GABA analogs.

Machine Learning for Quantum Mechanical Properties of Atoms in Molecules

We introduce machine learning models of quantum mechanical observables of atoms in molecules. Instant out-of-sample predictions for proton and carbon nuclear chemical shifts, atomic core level excitations, and forces on atoms reach accuracies on par with density functional theory reference. Locality is exploited within non-linear regression via local atom-centered coordinate systems. The approach is validated on a diverse set of 9k small organic molecules. Linear scaling of computational cost in system size is demonstrated for saturated polymers with up to sub-mesoscale lengths.

Effects of added salts on adsorbed film and premicelle formation of crown ether surfactants

Abstract Two crown ether surfactants, dodecanoyloxymethyl- (C11Φ5) and octanoyloxymethyl-15-crown-5 (C7Φ5), were synthesized and the concentration dependence of surface tension of their aqueous solutions was measured in the absence and the presence of various salts to study the effect of coexistent cation on adsorbed film and aggregation behavior of crown ether surfactants. In the absence of salt, the surface tension vs. concentration curves had two break points for both C11Φ5 and C7Φ5. The break point at the higher concentration (m0) was confirmed to be attributed to the micelle formation by the solubilization of water-insoluble dye and the concentration dependence of proton chemical shifts. Another break point at the lower concentration (mI) would be caused by the formation of premicellar aggregates. For C11Φ5 in the presence of KCl two break points were also observed. At about 0.05 mol kg−1 KCl, m0 and mI were minimized. The cause would be that the salting-out effect of KCl dominates below 0.05 mol kg−1 but above it the repulsive interaction between charged head groups of C11Φ5 complex with K+ becomes larger than it. Two break points were also observed for C11Φ5 in the presence of LiCl, NaCl, CsCl and NH4Cl of 0.22 mol kg−1. It has been found that the critical micelle concentration (m0) are the highest for Na+ having an ionic diameter comparable to the hole size of 15-crown-5 ring and decrease as an ionic diameter of added cation departs from the hole size. The aggregation number of premicelle, which was estimated from the surface excesses at mI and m0 on the assumption of two step micellization, has been about 4 in the absence of salt, about 3 for Li+ hydrated strongly and about 2 for all other cations.

Spectroscopic (FT-IR, 1H, 13C NMR and UV–vis) characterization and DFT studies of novel 8-((4-(methylthio)-2,5-diphenylfuran-3-yl)methoxy)quinoline

In this study, computational calculations of a new quinoline derivative: 8-((4-(methylthio)-2,5-diphenylfuran-3-yl)methoxy)quinoline is carried out using ab initio methods. The geometry optimization as well as fundamental frequencies of the most stable configuration of the title compound is reported. A detailed study of Infrared spectrum, chemical shifts and electronic spectrum of the title compound is also presented. The Gauge-Invariant Atomic Orbital approach is used to calculate the proton and carbon chemical shifts of the title compound. The natural bond orbital analysis of the title compound is also reported in order to understand the stability of the molecule which arises from hyper conjugative interactions and charge delocalization. The theoretical electronic absorption spectrum is also reported using the time dependent density functional approach. The molecular structure along with vibrational frequencies as simulated for binding of iron with the title compound is also reported using ab initio methods.