Magnetic field-induced effects on NMR properties.

In principle, all the NMR observables, spin-spin coupling J, nuclear shielding σ and quadrupole coupling q, are magnetic field-dependent. The field dependence may be classified into two categories: direct and indirect (apparent) dependence. The former arises from the magnetic field-induced deformation of the molecular electronic cloud, while the latter stems from a slightly anisotropic orientation distribution of molecules, due to the interaction between the anisotropy of the molecular susceptibility tensor and the external magnetic field. Here we use 1,3,5-D3-benzene as a model system to investigate the indirect effect on the one-bond 1H-13C and 2H-13C spin-spin couplings (J couplings) and the 2H quadrupole coupling. Experiments carried out at four magnetic fields (4.7, 9.4, 14.1, and 18.8 T) show that the indirect effect is significant already at the magnetic fields commonly used in NMR spectrometers. A joint fit of the data extracted at the different field strengths provides experimental results for the susceptibility anisotropy, 2H quadrupole coupling constant and the related asymmetry parameter, as well as the one-bond CH and CD coupling constants extrapolated to vanishing field strength. The field-induced contributions are found to exceed the commonly assumed error margins of the latter. The data also indicate a primary isotope effect on the one-bond CH coupling constant. There is a tendency to further increase the magnetic field of NMR spectrometers, which leads to more pronounced indirect contributions and eventually significant direct effects as well.

Benzene at 1GHz. Magnetic field-induced fine structure.

The deuterium NMR spectrum of benzene-d6 in a high field spectrometer (1GHz protons) exhibits a magnetic field-induced deuterium quadrupolar splitting Δν. The magnitude of Δν observed for the central resonance is smaller than that observed for the (13)C satellite doublets Δν'. This difference, Δ(Δν)=Δν'-Δν, is due to unresolved fine structure contributions to the respective resonances. We determine the origins of and simulate this difference, and report pulse sequences that exploit the connectivity of the peaks in the (13)C and (2)H spectra to determine the relative signs of the indirect coupling, JCD, and Δν. The positive sign found for Δν is consonant with the magnetic field biasing of an isolated benzene molecule-the magnetic energy of the aromatic ring is lowest for configurations where the C6 axis is normal to the field. In the neat liquid the magnitude of Δν is decreased by the pair correlations in this prototypical molecular liquid.

Electrical transport in ion beam created InAs nanospikes.

Ion beam irradiation has previously been demonstrated as a method for creating nanowire-like semiconductor nanostructures, but no previous studies have reported on the electrical properties of those structures. In this work we describe the creation and in situ transmission electron microscopy electrical characterization of nanoscale InAs spike structures on both InAs and InP substrates fabricated using a focused ion beam erosion method. Those InAs 'nanospikes' are found to possess internal structures with varying amounts of ion damaged and single crystalline material. Nanospike electrical behavior is analyzed with respect to model electronic structures and is similar to cases of barrier limited conduction in nanowires. The different electrical responses of each nanospike are found to be the result of variation in their structure, with the conductivity of InAs nanospikes formed on InAs substrates found to increase with the degree of nanospike core crystallinity. The conductivity of InAs nanospikes formed on InP substrates does not show a dependence on core crystallinity, and may be controlled by the other internal barriers to conduction inherent in that system.

Transmission electron microscopy of solution-processed, intrinsic and Al-doped ZnO nanowires for transparent electrode fabrication.

A solution-based chemistry was used to synthesize intrinsic and Al-doped (1% and 5% nominal atomic concentration of Al) ZnO nanostructures. The nanowires were grown at 300 degrees C in trioctylamine by dissolving Zn acetate and Al acetate. Different doping conditions gave rise to different nanoscale morphologies. The effect of a surfactant (oleic acid) was also investigated. An electron microscopy study correlating morphology, aspect ratio and doping of the individual ZnO wires to the electrical properties of the spin coated films is presented. HRTEM revealed single crystalline [0001] wires.

Spin-spin coupling tensors in fluoromethanes

All spin-spin coupling tensors J of the fluoromethanes CH3F, CH2F2, and CHF3 are obtained theoretically by multiconfiguration self-consistent field linear response (MCSCF LR) ab initio calculations. Furthermore the principal values and the orientation of the principal axis systems of each theoretical J tensor are specified. Experimental liquid crystal NMR (LC NMR) data on the tensorial properties of the CF spin spin coupling in CH3F and CH2F2, and the FF spin-spin coupling in CHF3 are also reported. In the analysis of the experiments, the contributions from molecular vibrations, as well as that of the correlation of vibrational and rotational motion to the experimental anisotropic couplings, D(exp), are taken into account. The information of the anisotropic indirect coupling, 1/2J(aniso), is detected as the difference between D(exp) and the calculated dipolar coupling, D(calc). The extracted indirect contributions, 1/2J(aniso), are in fair agreement with the ab initio results. All relative (experimental and theoretical) CF and FF indirect contributions, 1/2J(aniso)/D(exp), are negative and under 1.7% in magnitude, when the observed molecular orientations are used. Therefore, in the one bond CF couplings and in the two bond FF couplings, the indirect contribution can normally be ignored without introducing serious error to the determination of molecular orientation and/or structure. However, a more accurate method is to partially correct for the indirect contribution by utilising the transferability of the spin-spin coupling tensors in related molecules. This is due to the fact that even small contributions may be significant, if the order parameter of the internuclear direction is negligibly small, leading to dominating indirect contributions. The very good agreement of the experimental values with the calculated coupling constants and the reasonable agreement in the anisotropic properties, which are experimentally much more difficult to define, indicates that the MCSCF LR method is capable of producing reliable J tensors for these systems, contrary to the case of density-functional theory.

Assessment of cholesteryl ester transfer protein function in lipoprotein mixtures by 1H NMR spectroscopy.

Studies of cholesteryl ester transfer protein (CETP) function in lipoprotein mixtures pose many difficulties by conventional biochemical methods. For instance, studies on the effects of CETP on the composition of apolipoprotein B containing lipoproteins (very low and low density lipoproteins) in lipoprotein mixtures are tedious due to repeated ultracentrifugational isolations and have thus rarely been performed. Here we present a new 1H NMR spectroscopy technique to assess the CETP function in lipoprotein mixtures. This technique does not require repeated physical isolations of the lipoprotein particles but uses mathematical separation of the fractions on the basis of biochemical prior knowledge based lineshape fitting analysis of specific lipid resonances in the 1H NMR spectra. The lipoproteins are separated according to their size related chemical shift which allows for distinct quantification between very low and low density lipoproteins, the two major apolipoprotein B containing fractions. The methodological basis of the technique is discussed here together with a demonstration that this kind of approach allows dynamic follow up of the lipid transfer reactions in complex lipoprotein and CETP mixtures. The results revealed a consistent behaviour which corroborated the recent findings suggesting that the neutral lipid mass transfer among lipoproteins is not an equimolar heteroexchange.

Quantification of metabolites from single-voxel in vivo 1H NMR data of normal human brain by means of time-domain data analysis.

We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

1H NMR-based absolute quantitation of human lipoproteins and their lipid contents directly from plasma.

A new method is presented for absolute quantitation of lipid and protein contents of human lipoproteins directly from plasma. The method enables complete lipoprotein lipid profiles to be obtained in a total time of less than one hour. Absolute concentrations of triglycerides, phospholipids, total cholesterol, free cholesterol, esterified cholesterol, total proteins, and total masses can be estimated for the very low density (VLDL) and low density (LDL) lipoprotein fractions. For the high density lipoprotein (HDL) fraction all components except triglycerides can be quantitated. The method is a combination of 1H NMR spectroscopy and a sophisticated lineshape fitting analysis technique. In this paper we present the calibration of the method using 15 plasma samples followed by a double-blind test of 51 plasma samples from 43 individuals. In total, 66 plasma samples were analyzed. Comparison of the 1H NMR-based results with the data of the biochemical assays showed excellent agreement; the correlation coefficient for VLDL triglycerides was 0.98, for LDL cholesterol 0.88, and for HDL cholesterol 0.93. This method can be directly integrated to many kinds of biomedical NMR studies to offer additional biochemically important quantitative lipoprotein information, the measurement of which is usually too laborious by conventional biochemical methods and too high-priced to be adapted into the study protocols. Moreover, the method also has considerable potential to be developed for a routine clinical assay.

Time and frequency domain analysis of NMR data compared: an application to 1D 1H spectra of lipoproteins.

A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis algorithm (FITPLAC) for parameter estimation of magnetic resonance spectroscopy (MRS) data series is presented. VARPRO analyses the measured MRS signal (free induction decay; FID); FITPLAC analyses the discrete Fourier transform of the FID, the frequency domain magnetic resonance spectrum. A rapid time domain method, used to subtract the dominating water resonance from a 1H MRS FID, without affecting the metabolites of interest, is outlined and applied. Also a new "pseudofrequency selective" approach to time domain fitting is introduced. The possibilities of combining the most favorable features of time and frequency domain processing into one single MRS signal processing method are assessed. The 1H MRS signals of ultracentrifuged very low (VLDL), intermediate (IDL), and high (HDL) density lipoprotein fractions from human blood plasma were used for the comparisons. The results from both algorithms were in good agreement.

A comparative study of 1H NMR lineshape fitting analyses and biochemical lipid analyses of the lipoprotein fractions VLDL, LDL and HDL, and total human blood plasma.

The purpose of this work was two-fold. In the first instance, 1H NMR spectra of the ultracentrifuged lipoprotein fractions (VLDL, LDL and HDL) from six volunteers with different clinical conditions were measured. The methylene regions of the experimental spectra were modelled in the frequency domain using non-linear lineshape fitting analyses. In this way the resolvable Lorentzian component structures of the methylene regions of these lipoprotein fraction spectra could be determined. Second, the lipoprotein fraction analyses were used to construct simplified component structures, which interpreted the lipoprotein fraction spectra well, and were feasible to use in the total plasma spectra analyses. The considerable overlap problem of the resonances was properly handled in this way. The NMR-based relative amounts of the lipoproteins (relative integrated intensities of the lipoprotein model signals) obtained were compared to the biochemically resolved relative molar percentages of the lipoprotein fractions and also of the lipid contents between the lipoprotein complexes. It was noticed that nearly all correlations were extremely good. Thus, it is suggested that the developed methodology could be used as a fast method to predict the relative amounts of the lipoproteins and also possibly the relative lipid contents between the major lipoprotein categories directly from the proton NMR spectrum of a total blood plasma sample. Furthermore, if internal or external reference for the integrated intensities of the proton NMR resonances were used, it should also be possible to obtain the absolute amounts of these quantities.

Proton nuclear magnetic resonance lineshape studies on human blood plasma lipids from newborn infants, healthy adults, and adults with tumors.

The usefulness of proton NMR spectroscopy of human blood plasma for cancer research has been extensively studied in recent years. Two main starting points have been offered by Fossel et al. (N. Engl. J. Med. 315, 1369 (1986)) and Mountford et al. (FEBS Lett. 203, 164 (1986)). In this work the experimental proton NMR spectra of blood plasma were analyzed with the aid of the multivariate lineshape fitting method. An appropriate model structure, in terms of the various lipoprotein (VLDL, LDL, and HDL) signals, for the methylene region was used. Neonates, healthy adults, and adults with nonmalignant and malignant tumors were studied. The linewidth of the methylene region was found to be linearly dependent on the relative concentrations of the lipoproteins. The correlation coefficient was -0.89 (P less than 0.001) for VLDL and 0.88 (P less than 0.001) for HDL. A correlation between VLDL concentration and age, 0.76 (P less than 0.001), was also established. VLDL was modeled using two components. The half-linewidth of the lower field component was slightly elevated for the adults with large metastases. This might be in association with the fucose-containing proteolipid complex detected earlier in cancer cells or in sera of cancer patients. Some signals of this complex may fall in the same region of the spectra. The spectra for the neonates were indicated to be totally different from the adults. This and other related questions were explained by means of the model parameters and the relative concentrations of the lipoproteins VLDL, LDL, and HDL. The presented technique can be used as a rapid research tool for figuring out the relative concentrations of the lipoproteins in blood plasma and explaining the reasons behind the changes in the spectra.

A lineshape fitting model for 1H NMR spectra of human blood plasma.

A lineshape fitting model was constructed for classifying the overlapping information in the 1H NMR spectrum of human blood plasma. A reliable assignment of the overlapping fatty acid (-CH2-)n and -CH3 resonances of the various lipoproteins (VLDL, very low density lipoprotein; LDL, low density lipoprotein; HDL high density lipoprotein) is introduced, and for the first time detailed characteristics (chemical shifts, half linewidths, and relative intensities) of the individual lipoprotein components were obtained directly from the whole plasma spectrum. This was achieved by combining the constructed lineshape fitting model and the proper 400 MHz proton NMR measurements from blood plasma of a healthy donor, from fractions of the different lipoproteins, and from plasma samples in which the lipoprotein fractions were separately added. The results suggest fair promise of future applications of the rapid and easy NMR analysis of lipoprotein distribution in various research and clinical situations.

1H NMR studies on human plasma lipids from newborn infants, healthy adults, and adults with tumors.

The 1H NMR spectra of the lipid region of human plasma from healthy adults, neonates, and patients with malignant and nonmalignant tumors have been recorded on a JNM-GX400 FT spectrometer operating at 399.6 MHz for protons. The chemical shifts of methylene and methyl groups of plasma lipids were measured with respect to the higher field component of the methyl proton resonance of the lactate molecule. The results show that there are changes in the chemical shifts of the methylene proton resonances among the plasma from healthy adults, adults with tumors, and neonates. The shifts observed in the case of cancer patients and neonates are in the direction opposite to the shift measured from the plasma of healthy adults. Thus, the observed changes cannot be explained by the activity in the cell proliferation of tissues which is high in the cases of both healthy neonates and patients with malignant tumors, but they most probably reflect the different lipoprotein compositions of neonates, healthy adults, and adults with tumors.