Neutron diffraction, NMR and molecular dynamics study of glucose dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate

beta-D-glucose dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate in a 6 : 1 molar ratio (ionic liquid : glucose) has been studied by neutron scattering, NMR and molecular dynamics simulations. Good agreement was found between simulated neutron scattering profiles generated for isotopically substituted liquid systems and those experimentally determined as well as between simulated and experimental diffusion coefficients obtained by Pulsed Field Gradient NMR spectroscopy. The overriding glucose-ionic liquid interactions in the liquid are hydrogen-bonding between acetate oxygens and sugar hydroxyl groups. The ionic liquid cation was found to play only a minor role in the solvation of the sugar and does not participate in hydrogen-bonding with the sugar to any significant degree. NOESY experiments lend further evidence that there is no direct interaction between sugar hydroxyl groups and acidic hydrogens on the ionic liquid cation.

Metabolic signatures of human Alzheimer's disease (AD): H-1 NMR analysis of the polar metabolome of post-mortem brain tissue

Brain tissue from so-called Alzheimer's disease (AD) mouse models has previously been examined using H-1 NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first H-1 NMR-metabolomics investigation of human AD brain tissue. Human post-mortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using H-1 NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4 %) and taurine (18.9 %) were observed in AD patients (p ≤ 0.05). Pathway topology analysis implicated either dysregulation of taurine and hypotaurine metabolism or alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD [receiver operating characteristic (ROC) AUC <0.67; p < 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p < 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic

Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in Type 1 diabetes

Our objective is to define differences in circulating lipoprotein subclasses between intensive vs. conventional management of Type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). Nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of five (interquartile range: four, six) years following randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSP between treatment groups. Standard total-, LDL- and HDL-cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSP showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, p=0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, p=0.007), total IDL/LDL (mean: 1000 vs. 1053 nmol/l, p=0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, p<0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 μmol/l, p=0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

Compartmentalized Cerebral Metabolism of [1,6-(13)C]Glucose Determined by in vivo (13)C NMR Spectroscopy at 14.1 T.

Cerebral metabolism is compartmentalized between neurons and glia. Although glial glycolysis is thought to largely sustain the energetic requirements of neurotransmission while oxidative metabolism takes place mainly in neurons, this hypothesis is matter of debate. The compartmentalization of cerebral metabolic fluxes can be determined by (13)C nuclear magnetic resonance (NMR) spectroscopy upon infusion of (13)C-enriched compounds, especially glucose. Rats under light α-chloralose anesthesia were infused with [1,6-(13)C]glucose and (13)C enrichment in the brain metabolites was measured by (13)C NMR spectroscopy with high sensitivity and spectral resolution at 14.1 T. This allowed determining (13)C enrichment curves of amino acid carbons with high reproducibility and to reliably estimate cerebral metabolic fluxes (mean error of 8%). We further found that TCA cycle intermediates are not required for flux determination in mathematical models of brain metabolism. Neuronal tricarboxylic acid cycle rate (V(TCA)) and neurotransmission rate (V(NT)) were 0.45 ± 0.01 and 0.11 ± 0.01 μmol/g/min, respectively. Glial V(TCA) was found to be 38 ± 3% of total cerebral oxidative metabolism, accounting for more than half of neuronal oxidative metabolism. Furthermore, glial anaplerotic pyruvate carboxylation rate (V(PC)) was 0.069 ± 0.004 μmol/g/min, i.e., 25 ± 1% of the glial TCA cycle rate. These results support a role of glial cells as active partners of neurons during synaptic transmission beyond glycolytic metabolism.

The power of NMR. Part 1: the beginnings

Nuclear mnagnetic resonance (NMR) spectroscopy involves the excitation of nuclei by electromagnetic radiation in the radio-frequency range of the electromagnetic spectrum. For a nucleus to absorb energy from radiowaves in this way, it must hve the quantum mechanical property of spin. A spinning nucleus, such as that of the hydrogen atom, will dopt one f only two possible states when placed in a magnetic field. (In NMR, the hydrogen nucleus is often referred to as a proton, and is given the abbreviation 1H.) Az the strength of the magnetic field is increased, there is a proportional increase in the energy 'gap' between these two states. We can predic the resonant frequency at which any spinning nucleus will absorb energy from radio-frequency radiation as it jumps from the lower energy state to the upper state.

Diastereoselective formation of 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines: an X-ray crystallographic and 1H NMR study

N-Arylsulfonamides of (R)- and (S)-2-amino-1-butanol, on condensation with aromatic aldehydes produced diastereomerically pure 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines. The absolute configurations of one enantiomeric pair have been determined from two fully refined X-ray structures, supplemented by nmr data.

Evidence for magnetic phase separation in La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) manganites from NMR and magnetic measurements

Polycrystalline La(0.86)Sr(0.14)Mn(1-x)Cu(x)O(3+delta) (x = 0, 0.05, 0.10, 0.15, 0.20) manganites were investigated by means of magnetic measurements and zero-field (139)La and (55)Mn nuclear magnetic resonance (NMR) spectroscopy. Magnetization versus temperature measurements revealed a paramagnetic to ferromagnetic transition in most samples, with lower Curie temperatures and broader transitions for samples with higher Cu contents. The details of the magnetization measurements suggested a phase-separated scenario, with ferromagnetic clusters embedded in an antiferromagnetic matrix, especially for the samples with large Cu contents (x = 0.15 and 0.20). Zero-field (139)La NMR measurements confirmed this finding, since the spectral features remained almost unchanged for all Cu-doped samples, whereas the bulk magnetization was drastically reduced with increasing Cu content. (55)Mn NMR spectra were again typical of ferromagnetic regions, with a broadening of the resonance line caused by the disorder introduced by the Cu doping. The results indicate a coexistence of different magnetic phases in the manganites studied, with the addition of Cu contributing to the weakening of the double-exchange interaction in most parts of the material.

63Cu NMR investigation of effect of small additions of Sn to Al-1.7 at.%Cu in promoting accelerated phase transformations on aging

Very recently 63Cu NMR has been shown to be extremely sensitive in detecting and differentiating between the precipitate phases that form in Al-Cu alloys during heat treatment. This technique is now used to quantify the effectiveness of small additions of Sn to the alloy Al-1.7 at.% Cu in promoting the rapid nucleation and growth of the θ'-phase precipitate. Two parallel series of 63Cu NMR spectra were recorded for Al-1.7 at.% Cu and Al-1.7 at.% Cu-0.01 at.% Sn: (i) aged at 130° C to observe the comparative rate of phase evolution and (ii) aged at 200° C to observe the rate of growth of θ'-phase and to compare with the Vickers hardness of the alloys aged at 200° C for similar periods. Evidence is presented that a metastable precursor phase to θ' (labelled TPHM2757math001) is formed in Al-Cu-Sn which transforms to θ' on further aging.