Conventional NMR Spectroscopy Research Articles

NMR spectroscopic studies of cellobiose solvation in EmimAc aimed to understand the dissolution mechanism of cellulose in ionic liquids

The dissolution mechanism of cellulose in ionic liquids has been investigated by using cellobiose and 1-ethyl-3-methylimidazolium acetate (EmimAc) as a model system under various conditions with conventional and variable-temperature NMR spectroscopy. In DMSO-d(6) solution, NMR data of the model system clearly suggest that hydrogen bonding is formed between hydroxyls of cellobiose and both anion and cation of EmimAc. The CH(3)COO(-) anion favors the formation of hydrogen bonds with hydrogen atoms of hydroxyls, and the aromatic protons in bulky cation [Emim](+), especially the most acidic H2, prefer to associate with the oxygen atoms of hydroxyls with less steric hindrance, while after acetylation of all hydroxyls in cellobiose the interactions between cellobiose octaacetate and EmimAc become very weak, implying that hydrogen bonding is the major reason of cellobiose solvation in EmimAc. Meanwhile the stoichiometric ratio of EmimAc/hydroxyl is estimated to be between 3:4 and 1:1 in the primary solvation shell, suggesting that there should be one anion or cation to form hydrogen bonds with two hydroxyl groups simultaneously. In situ and variable-temperature NMR spectra suggest the above mechanism also works in the real system.

Diversity-Oriented Synthesis of Angular Bis-benzimidazole Derivatives under Microwave Irradiation

Pharmaceutically interesting, angular bis-benzimidazoles with three appendages have been synthesized successfully through a diversity-oriented approach with soluble support under microwave irradiation. Polymer immobilized o-phenylenediamine was selectively N-acylated with 2-chloro-3-nitrobenzoic acid in a primary aromatic amino moiety. The obtained amide was cyclized to benzimidazole in an acidic condition, and subsequently nucleophilic aromatic substitution with different amines was performed. Successive reduction, cyclization with various aldehydes and activated isothiocyanates yielded angular biheterocyclic benzimidazoles in good quantities. Reaction progress on polymer support was precisely monitored using the conventional proton NMR spectroscopy. Preliminary screening results showed some of these interesting compounds exhibited moderately to good inhibition against vascular endothelial growth factor receptor 3 (VEGFR-3), which is related to invasion and migration of cancer cells.

General Strategy for High-Density Covalent Functionalization of Diamond Nanoparticles Using Fenton Chemistry

Diamond nanoparticles (npD) from detonation do not undergo covalent functionalization to a large extent, as assessed by conventional IR and NMR spectroscopy. This low level of surface modification is due to the low density of surface hydroxyl groups and the presence of soot matter covering npD. We have found that the Fenton reaction of npD remarkably increases the density of surface OH groups, decreases the undesirable amorphous soot matter, and makes possible the subsequent high-density covalent functionalization of these nanoparticles. In this way, the polarity and solubility of npD can be controlled and, besides by IR spectroscopy, we have shown that it is even possible to characterize the resulting diamond nanoparticles by conventional solution 1H NMR spectroscopy in which the signals corresponding to the proton ligands can be monitored.

Panorganismal metabolic response modeling of an experimental Echinostoma caproni infection in the mouse.

Metabolic profiling of host tissues and biofluids during parasitic infections can reveal new biomarker information and aid the elucidation of mechanisms of disease. The multicompartmental metabolic effects of an experimental Echinostoma caproni infection have been characterized in 12 outbred female mice infected orally with 30 E. caproni metacercariae each, using a further 12 uninfected animals as a control group. Mice were killed 36 days postinfection and brain, intestine (colon, ileum, jejeunum), kidney, liver, and spleen were removed. Metabolic profiles of tissue samples were measured using high-resolution magic angle spinning 1H NMR spectroscopy and biofluids measured by applying conventional 1H NMR spectroscopy. Spectral data were analyzed via principal component analysis, partial least-squares-derived methods and hierarchical projection analyses. Infection-induced metabolic changes in the tissues were correlated with altered metabolite concentrations in the biofluids (urine, plasma, fecal water) using hierarchical modeling and correlation analyses. Metabolic descriptors of infection were identified in liver, renal cortex, intestinal tissues but not in spleen, brain or renal medulla. The main physiological change observed in the mouse was malabsorption in the small intestine, which was evidenced by decreased levels of various amino acids in the ileum, for example, alanine, taurine, glutamine, and branched chain amino acids. Furthermore, altered gut microbial activity or composition was reflected by increased levels of trimethylamine in the colon. Our modeling approach facilitated in-depth appraisal of the covariation of the metabolic profiles of different biological matrices and found that urine and plasma most closely reflected changes in ileal compartments. In conclusion, an E. caproni infection not only results in direct localized (ileum and jejenum) effects, but also causes remote metabolic changes (colon and several peripheral organs), and therefore describes the panorganismal metabolic response of the infection.

Use of Protonless NMR Spectroscopy To Alleviate the Loss of Information Resulting from Exchange-Broadening

We report here the use of protonless NMR spectroscopy to extract structural information under biologically relevant conditions when conventional proton-detection NMR spectroscopy fails due to the loss of labile proton resonances. By direct (13)C detection, correlations between nonlabile nuclei of a given biomolecule can be determined with high resolution, which becomes particularly useful when the system of interests is sensitive to solvent exchange at elevated temperatures, such as intrinsically disordered proteins. Human alpha-synuclein, which is associated with Parkinson's disease, is used as a model system to illustrate the usefulness of protonless NMR spectroscopy in recovering hitherto missing spectral information.

Sequentially acquired two-dimensional NMR spectra from hyperpolarized sample

A scheme capable of acquiring heteronuclear 2D NMR spectra of hyperpolarized sample is described. Hyperpolarization, the preparation of nuclear spins in a polarized state far from thermal equilibrium, can increase the NMR signal by several orders of magnitude. It presents opportunities to apply NMR spectroscopy to dilute samples that would otherwise yield insufficient signal. However, conventional 2D NMR spectroscopy, which is commonly applied for the determination of molecular structure, relies on the recovery of the initial polarization after each transient. For this reason, it cannot be applied directly to a sample that has been hyperpolarized once. With appropriately modified pulse schemes, two-dimensional NMR spectra an however be acquired sequentially by utilizing a small portion of the hyperpolarized signal in every scan, while keeping the remaining polarization for future scans. We present heteronuclear multi-quantum spectra of single hyperpolarized samples using this technique, and discuss different options for distributing the polarization among different scans. This robust method takes full advantage of Fourier NMR to resolve overlapping chemical shifts, and may prove particularly useful for the structural elucidation of compounds in mass-limited samples.

NMR‐based Metabonomic Study on Rat's Urinary Metabolic Response to Dosage of Triptolide

AbstractAn NMR‐based metabonomic approach was used to examine rat's urinary response to dosage of triptolide (TP), a major component responsible for the immunosuppressive and anti‐inflammatory effects of Tripterygium wilfordii Hook F (TWHF). The urine samples of Wistar rats were collected at various time intervals before and after dosage of TP (i.p.) and measured using conventional 1H NMR spectroscopy. The data were statistically analyzed using a principle component analysis (PCA). The results showed that biochemical variation induced by TP was time‐related, and the maximal alteration in the metabolites appeared at 16 h, and partially recovered 56 h later after dosage. Increment in relative concentrations of taurine, creatine, trimethylamine N‐oxide and decrement in citrate, succinate, 2‐oxoglutarate and hippurate were observed in the urine after dosage of TP. In addition, 2'‐deoxycytidine appeared 0–16 h later after the dosage, which may be considered as another biomarker for the acute hepatotoxicity. It suggested that TP may disturb the metabolism of energy and gut microflora, and may cause acute liver lesion and a slight renal impair. These results were also supported by the conventional analysis of clinical plasma chemistry and histopathology. The information observed in this article may be useful for giving insight into mechanism of liver injury induced by TP.

Observation of silane coupling agents adsorbed on silica by solid state 1H NMR under fast magic angle spinning

The spectroscopy of the adsorbed silane coupling agent on micro-sized silica particles was observed by 1H solid state NMR (SSNMR) under fast magic angle spinning (MAS). We found that this is a fast and effective way to characterize the structure and dynamics of the thin layer of coupling agent on the surface of micro-sized silica. Compared with conventional 29Si NMR spectroscopy and other methods, the present proton solid state NMR is a promising method to characterize the adsorbed layer on micro-sized silica.

Differentiation of hydroxyl-aluminum species at lower OH/Al ratios by combination of 27Al NMR and Ferron assay improved with kinetic resolution

The hydroxyl-Al polymers are the most effective components in PACl coagulants, but their chemical speciation is often indistinct especially at lower molar OH/Al ratios ( B). Two sets of hydroxyl-Al solutions with different B values and preparation temperatures were studied with both Ferron assay and 27Al NMR spectroscopy. By using the modified kinetic resolution procedure to fit the scanning absorbance data, the reactive polymeric Al species (Al b) could be differentiated further into two fractions: the faster reacting polymers Al b1 and slower reacting polymers Al b2. They were distinguished by their distinct rate constants of reactions with Ferron. It was identified simultaneously by the 27Al NMR spectroscopy that the Al b2 fraction closely corresponded to Al 13 of Keggin-structure in most samples, while the Al b1 at the moderate OH/Al ratios of B < 2 would be assigned to the species of Al 6-type series which were undetectable in current 27Al NMR spectrum (Al un). Conventional 27Al NMR spectroscopy in combination with Ferron assay improved with kinetic resolution can better explore the chemical speciation for hydroxyl-Al polymers in partially neutralized Al solutions and thus give a better explanation of coagulation mechanisms of these species when they were applied in water treatment.

Local electronic structure inMgB2fromB12β-NMR

We performed $\ensuremath{\beta}$-NMR spectroscopic studies on $^{12}\mathrm{B}$ which was implanted into $\mathrm{Mg}{\mathrm{B}}_{2}$ to get insight into the local electronic structure of this high-temperature superconducting material. By measuring electric field gradients we probed the electronic charge distribution anisotropy around boron in this solid and thus obtained experimental information about the bonding by $p$ electrons. Besides the absolute value, the sign of the electric field gradient was also experimentally determined. By comparison with quantum chemical calculations, some of which were performed in the present work, and with results from conventional NMR spectroscopy on $^{11}\mathrm{B}$ we were able to identify regular boron lattice sites as well as interstitial sites.

Simultaneous Encapsulation: Molecules Held at Close Range

AbstractFor Abstract see ChemInform Abstract in Full Text.

Simultaneous Encapsulation: Molecules Held at Close Range

Reversible encapsulation creates spaces where molecules are temporarily isolated from others in solution. Molecules are held within the space of the capsule for lifetimes ranging from milliseconds to hours, and conventional NMR spectroscopy can be used to report on the chemical and magnetic environment as well as the arrangement of the molecules in the encapsulation complex. The complexes self-assemble when, and only when, the spaces inside the capsules are appropriately filled. The weak intermolecular forces that hold these self-assemblies together allow equilibration of the encapsulation complexes at ambient temperatures and pressures in the liquid phase. When two or more molecules are simultaneously encapsulated, intermolecular phenomena are revealed in solution that cannot be observed by other methods. We describe here the unique behavior that emerges from molecules that are simultaneously encapsulated and includes new forms of stereochemistry, isomerism, and asymmetry inside capsules.

A simple approach for phase-modulated single-scan 2D NMR spectroscopy

Conventional NMR spectroscopy techniques require long acquisition times due to the recovery time between the repeated excitations necessary for each increment of the evolution times in the indirectly detected dimensions. Here we outline a pulse sequence element for gradient-assisted ultrafast multidimensional NMR spectroscopy using frequency-modulated 'chirp' pulses to generate phase-modulated magnetization in an indirectly detected spectral dimension. The potential of this sequence element is demonstrated by acquiring a correlation spectroscopy (COSY) spectrum in 96 ms. This new pulse sequence element is an extension of ultrafast spectroscopy techniques based on the generation of amplitude modulation of the NMR signal in the indirectly detected spectral dimensions. The use of phase modulation instead of amplitude modulation helps broaden the applicability and may provide an increase of sensitivity in some experiments due to the ability to distinguish between positive and negative frequency offsets relative to the carrier frequency of the sequence element.

Liquid-phase combinatorial reaction monitoring by conventional 1H NMR spectroscopy

The application of 1H NMR spectroscopy for complete analysis of soluble polymer-supported reactions is described. This conventional analytical technique enables us to determine the extent of liquid-phase reactions without cleavage of the soluble matrix. The polymer matrix permitted us to obtain 1H NMR spectra with a resolution comparable with that of spectra of the molecule in solution.

Synthesis of end- and mid-Phthalic Anhydride Functional Polymers by Atom Transfer Radical Polymerization

Polystyrene (PS) and poly(methyl methacrylate) (PMMA) having a single di-tert-butyl phthalate (DTBP) group either at the chain end or in the middle of the chain were synthesized by Cu(I) ion mediated atom transfer radical polymerization (ATRP). The di-tert-butyl phthalate initiators 7 and 8 (for end-functional polymers) and 11 (for mid-functional polymers) were prepared from commercially available di-tert-butyl acetylene dicarboxylate (1) and myrcene (2) in four and six steps, respectively, with high overall yields. The DTBP functionalized polymers could be cleanly converted to the corresponding phthalic anhydride (PA) functional polymers by pyrolysis. The pyrolysis process could be easily monitored using conventional 1H NMR spectroscopy, by observing the significant chemical shift change of the alkyl linker existing in the initiators. Kinetic study of the pyrolysis revealed that the mechanism of the DTBP group pyrolysis to phthalic anhydride (PA) group follows two first-order consecutive reactions having a phthalic diacid (DA) as an observable intermediate. When the PA-functionalized PMMA was subjected to reactive blending at 180 °C with an amine-functionalized PS, the conversion reached a maximum (>90%) in less than 2 min, which is considerably faster than the corresponding reaction of an aliphatic anhydride (e.g., succinic anhydride)-functionalized PMMA. A competition experiment with small molecules showed that phthalic anhydride reacts 5 times faster than succinic anhydride with PS-NH2.

Unique poly(glycerophosphate) lipoteichoic acid and the glycolipids of a Streptococcus sp. closely related to Streptococcus pneumoniae.

The Streptococcus sp. studied here is closely related to Streptococcus pneumoniae with 98.6% 16S rRNA similarity and 65% DNA/DNA homology. We isolated the lipoteichoic acid and the membrane glycolipids whose structures were established using conventional procedures and NMR spectroscopy. The lipoteichoic acid contains a linear 1,3-linked poly(glycerophosphate) chain which is partly substituted with D-alanine ester and is phosphodiester-linked to O6 of beta-D-Galf(1-->3)acyl2Gro. This lipoteichoic acid is the first example in which a monohexosylglycerol serves as the glycolipid anchor; and with an average chain length of 10 glycerophosphate residues it is the shortest known to date. MS analysis, applied for the first time to a native acylated lipoteichoic acid, revealed a continuous increase in chain length from seven to 17 glycerophosphate residues with a maximum at 10, and allowed identification of the fatty acid combinations. Membrane glycolipids consisted of beta-D-Galf(1-->3)acyl2Gro (9%), alpha-D-Glcp(1-->3)acyl2Gro (22%), alpha-D-Galp(1-->2)-alpha-D-Glcp(1-->3)acyl2Gro (64%) and alpha-D-Galp(1-->2)-(6-O-acyl)-alpha-D-Glcp(1-->3)acyl2Gro (5%). It is noteworthy that in lipoteichoic acid biosynthesis, Galfacyl2Gro, a less abundant membrane glycolipid, is selected as the lipid anchor. Despite the genetic relatedness to Streptococcus pneumoniae, the lipoteichoic acid structure is quite different to the complex structure of pneumococcal lipoteichoic acid [T. Behr et al. (1992) Eur. J. Biochem. 207, 1063-1075], thus providing an example that minor differences in DNA sequence exert major changes in macromolecular structure.

Exploring Macromolecular Interactions at High Resolution Using Electron Cryomicroscopy at NCMI

The National Center for Macromolecular Imaging (NCMI) is a resource supported by the National Center for Research Resources (NCRR) of NIH. Its mission is to advance electron imaging of macromolecular assemblies to near atomic resolution. We have focused on biological assemblies which are too large or too complex to be studied by conventional x-ray crystallography or NMR spectroscopy techniques. As is the case with all the NCRR-supported facilities, we also conduct methodology development, collaboration, service, technology dissemination and training.The objectives of this Research Resource are to develop the technology of high resolution electron cryomicroscopy of biological macromolecules, assemblies and crystals in an integrated approach that includes specimen preparation, hardware and software development. A current methodology development includes the characterization of the 1k x 1k slow-scan CCD camera for both electron diffraction and imaging of ice-embedded specimens. These studies have defined the advantages and limitations of the CCD camera for electron crystallographic analysis. Another core research project deals with the problems of specimen movement due to the electron beam and/or charging and seeks to minimize these phenomena. Our efforts have resulted in a better understanding of the physics of charging. We have modified a Gatan ion-beam coater so that we can apply a thin layer of carbon onto ice-embedded specimens.

H and 13C Nuclear Magnetic Resonance Studies on the Stereochemical Configuration of Bis(N,N-dimethyl-2,4-dimethylglutarylamide) and Poly(N,N-dimethylacrylamide)

The conformation and configuration analysis of the dimer bis(N,N-dimethyl-2,4-dimethylglutarylamide) was carried out by means of both conventional 1H and 13C NMR spectroscopy and advanced (INEPTLR and 2D HETCOR) methods. The γ-gauche effect method appears to reproduce the observed chemical shift difference between m- and r-isomers. Stereochemical structure of poly(N,N-dimethylacrylamide) (PDMAA) was studied using proton spectrum (at the triad level) and DEPT spectra (at the triad and pentad level). For PDMAA prepared by radical polymerization, the Bernoullian statistics are required to fit the observed intensities at the pentad level.

NMR studies of molecular mobility and diffusion in porous systems

The uptake, partitioning, and release of ingredients such as water, oil, surfactant, and ions are important factors to understand and control in the design and manufacture of detergent and personal products. Although conventional pulse NMR (PNMR) spectroscopy continues to be used to analyse bulk molecular mobility and phase composition, more recently MR imaging techniques have created unique opportunities for gaining spatial information about these processes in ways that are noninvasive and potentially quantitative. This paper describes the evaluation of MRI and associated PNMR techniques to study transport in three relevant cases: ion diffusion (e.g., fluoride) in concentrated dispersions, oil transport through powders, and water ingress into porous powders (zeolite). Results are presented to illustrate the potential of multiple pulse and gradient echo MRI methods for dealing with the short T 2 scenarios that represent a common problem in quantitative imaging of water in solid-containing composites involving, for instance, zeolite, or silica. Pore-size characterisation results are also presented.

Primary structure of the oligosaccharide chain of lipopeptidophosphoglycan of epimastigote forms of Trypanosoma cruzi.

The lipopeptidophosphoglycan of epimastigote forms of Trypanosoma cruzi is composed of a glycan linked through a non-N-acetylated glucosamine residue to an inositol phosphorylceramide. Using conventional analysis techniques, including 1H, 13C, and 31P NMR spectroscopy and negative ion fast atom bombardment mass spectroscopy, the structure of the carbohydrate-containing part of the molecule is determined as: (Sequence: see text). There is uncertainty as to which 2-O-substituted alpha-D-Manp unit is attached the side chain or whether it is distributed between the two units. Some of the structures lack the Galf side chain. The inositol unit is linked to ceramide via a phosphodiester bridge. The major aliphatic components of the ceramide portion were lignoceric acid and sphinganine.