1H Magic Angle Spinning Research Articles

Surface modification of calcium carbonate with phosphonic acids

The surface of precipitated calcite particles was modified by reaction with phosphonic acids (phenylphosphonic acid and dodecylphosphonic acid) in organic solvents, tetrahydrofuran (THF) and ethanol. The reaction kinetics and adsorption isotherms were determined. Under appropriate conditions, dense phosphonate monolayers were deposited at the surface of the CaCO3 particles. The nature of the grafted species was investigated using 31P and 1H Magic Angle Spinning (MAS) solid state NMR spectroscopy, FTIR spectroscopy and N2 physisorption. These monolayers were found to increase the hydrophobic character of CaCO3 surfaces, especially in the case of dodecylphosphonic acid. The unwanted formation of a bulk crystalline calcium phosphonate phase by dissolution–precipitation was observed only in the reaction of phenylphosphonic acid with CaCO3 in THF, and it could be largely avoided by working at low concentration of the phosphonic acid and/or minimizing reaction times to less than 3 days.

Distribution, Orientation and Dynamics of 17β-Estradiol in Lipid Membranes Investigated by Solid-State NMR

17β-Estradiol (E2) is a potent estrogen, which modulates many important cellular functions by binding to specific estrogen receptors located in the cell nucleus and also on the plasma membrane. We have studied the interaction of E2 with POPC membranes using a combination of solid-state NMR methods. Investigations were conducted on powder-type samples at lipid/E2 ratios of 5:1 and 10:1 and at a temperature of 303K. Information about the chain dynamics and membrane packing properties was obtained using 2H solid-state NMR. The spectra indicate that E2 does not cause a condensation effect of the surrounding phospholipids, which is contrary to the effects of cholesterol, and only very modest E2 induced alterations of the membrane structure were detected. 1H magic-angle spinning NMR showed well resolved signals from E2 as well as of POPC in the membrane-lipid layer. Two-dimensional NOESY spectra revealed intense cross-peaks between E2 and the membrane lipids indicating that E2 is stably inserted into the membrane. The determination of intermolecular cross-relaxation rates revealed that E2 is broadly distributed in the membrane with a maximum of the E2 distribution function in the upper chain region of the membrane. To further establish the orientation and dynamics of E2 we obtained a variant in which four hydrogens were replaced by deuterium and recorded corresponding 2H NMR spectra. The analysis of these spectra was performed by a model describing the orientation and dynamics of E2 in the membrane. We determined its average orientation in the membrane and conclude that E2 is highly dynamic in lipid membranes and may undergo rotations as it exhibits two polar hydroxyl groups on either side of the molecule.

“Grafting From” Polymerization of Vinylidene Fluoride (VDF) from Silica to Achieve Original Silica–PVDF Core–Shells

A new method of surface modification based on the “grafting from” polymerization process enabled to prepare original silica nanoparticles covered with PDVF “hair”. This strategy involved two steps: (i) the radical addition of 1,4-diiodoperfluorobutane initiated by tert-butylperoxypivalate onto the double bonds of silica nanoparticles (specific area of 150 m2 g–1) led to silica that bore C4F8I end-groups on its surface, and (ii) its use as original macrochain transfer agent in the “grafting from” polymerization of vinylidene fluoride (VDF) initiated by bis(4-tert-butylcyclohexyl) peroxydicarbonate. The characterizations of both modified silica were achieved by elemental analysis, 1H and 19F magic angle spinning solid state rotational-echo double resonance NMR spectroscopy, thermogravimetry, and water contact angle (WCA) assessments. The grafting efficiency was confirmed by three features: (i) the increase of weight percentage of fluorine atom (that ranged from 0 for the starting unsaturated silica to 2.50% for silica-bearing −C4F8I end-group and to 3.32% for original silica–PVDF core–shells), (ii) a high thermostability (that reached more than 400 °C under air), and (iii) a good hydrophobicity: the WCA values were ranging from 84° to 109° and to 126° for vinyl silica, for silica coated with −C4F8I, and for PVDF-covered silica nanoparticles, respectively.

Solid-State P and H NMR Investigations of Amorphous and Crystalline Calcium Phosphates Grown Biomimetically From a Mesoporous Bioactive Glass.

By exploiting 1H and 31P magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy, we explore the proton and orthophosphate environments in biomimetic amorphous calcium phosphate (ACP) and hydroxy-apatite (HA), as grown in vitro at the surface of a 10CaO–85SiO2–5P2O5 mesoporous bioactive glass (MBG) in either a simulated body fluid or buffered water. Transmission electron microscopy confirmed the presence of a calcium phosphate layer comprising nanocrystalline HA. Two-dimensional 1H–31P heteronuclear correlation NMR established predominantly 1H2O↔31PO43– and O1H↔31PO43– contacts in the amorphous and crystalline component, respectively, of the MBG surface-layer; these two pairs exhibit distinctly different 1H→31P cross-polarization dynamics, revealing a twice as large squared effective 1H–31P dipolar coupling constant in ACP compared with HA. These respective observations are mirrored in synthetic (well-crystalline) HA, and the amorphous calcium orthophosphate (CaP) clusters that are present in the pristine MBG pore walls: besides highlighting very similar local 1H and 31P environments in synthetic and biomimetic HA, our findings evidence closely related NMR characteristics, and thereby similar local structures, of the CaP clusters in the pristine MBG relative to biomimetic ACP.

Biphenylene units possessing flammable and nonflammable characteristics in fluoroalkyl end-capped vinyltrimethoxysilane oligomeric silica gel matrices after calcination at 800 °C

Two kinds of fluoroalkyl end-capped vinyltrimethoxysilane oligomer [RF-(VM)n-RF] silica nanocomposites containing biphenylene units were prepared by the sol-gel reactions of the corresponding oligomer with biphenylene-bridged ethoxysilanes or 4,4′-biphenol under alkaline conditions, respectively. One is the fluorinated oligomer/silica nanocomposites containing biphenylene units [RF-(VM-SiO2)n–RF/Ar-SiO2], of whose biphenylene units were incorporated into nanocomposite cores through the siloxane bondings, and the other is the fluorinated oligomer/silica nanocomposites containing biphenylene units [RF-(VM-SiO2)n–RF/Biphenol], of whose biphenylene units were directly encapsulated into nanocomposite cores through the sol–gel process. Interestingly, the shape of RF-(VM-SiO2)n–RF/Ar-SiO2 nanocomposites is morphologically controlled cubic particles; although the shape of RF-(VM-SiO2)n–RF/Biphenol nanocomposites is spherically fine particles. Thermogravimetric analyses 2H magic-angle spinning nuclear magnetic resonance, Ultraviolet visible, and fluorescent spectra showed that biphenylene units in RF-(VM-SiO2)n–RF/Ar-SiO2 nanocomposites have a flammable characteristic after calcinations at 800 °C; in contrast, biphenylene units in RF-(VM-SiO2)n–RF/Biphenol nanocomposites have a nonflammable characteristic even after calcination at 800 °C. X-ray photoelectron spectroscopy analyses of these two kinds of fluorinated nanocomposites showed that nonflammable characteristic toward biphenylene units in the silica gel matrices is due to the formation of ammonium hexafluorosilicate during the sol–gel process.

P103 Metabolic profiling of the rat liver after chronic ingestion of α-naphthylisothiocyanate using in vivo and ex vivo magnetic resonance spectroscopy

IntroductionHepatobiliary injury, associated with intrahepatic cholestasis and biliary hyperplasia, is a commonly encountered adverse effect in man in response to certain drugs and toxins. Some human diseases affecting the biliary...

Controlled atmosphere 13C and 1H MAS NMR study of reforming route of methane with carbon dioxide over Rh/SBA-15

The mechanism of methane reforming with carbon dioxide over 1.0 wt.% Rh/SBA-15 catalyst has been studied by the 13C and 1H magic-angle spinning (MAS) NMR spectroscopies under controlled atmosphere condition using 13CH 4 + 12CO 2 and 12CH 4 + 13CO 2 as reactants. The effect of temperature in the region of 298–1023 K on the reaction was investigated and the contents of various 13C and 1H species were obtained quantitatively by the NMR technique. When treated at 573 K, the carbon exchange between methane and carbon dioxide can be observed. With the temperature rising to 773 K, the adsorbed CH 3O* species is formed but no reforming reaction occurs. In the high temperature range of 873–1023 K, the reforming reaction was observed with concomitant appearance of the adsorbed CH 2O* species and the intensity of both CH 3O* and CH 2O* increases with increasing temperature, indicating that the decomposition of CH 3O* to CH 2O* occurs and the products of dry reforming are formed from decomposition of the adsorbed CH 2O* species.

Bulk magnetization and 1H NMR spectra of magnetically heterogeneous model systems

Bulk magnetization and 1H static and magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectra of two magnetically heterogeneous model systems based on laponite (LAP) layered silicate or polystyrene (PS) with low and high proton concentration, respectively, and ferrimagnetic Fe2O3 nano- or micro-particles have been studied. In LAP+Fe2O3, a major contribution to the NMR signal broadening is due to the dipolar coupling between the magnetic moments of protons and magnetic particles. In PS+Fe2O3, due to the higher proton concentration in polystyrene and stronger proton–proton dipolar coupling, an additional broadening is observed, i.e. 1H MAS NMR spectra of magnetically heterogeneous systems are sensitive to both proton–magnetic particles and proton–proton dipolar couplings. An increase of the volume magnetization by ∼1emu/cm3 affects the 1H NMR signal width in a way that is similar to an increase of the proton concentration by ∼2×1022/cm3. 1H MAS NMR spectra, along with bulk magnetization measurements, allow the accurate determination of the hydrogen concentration in magnetically heterogeneous systems.

Study on metabonomic characteristics of human lung cancer using high resolution magic‐angle spinning 1H NMR spectroscopy and multivariate data analysis

Lung cancer causes serious health problems. Clinical diagnosis of lung cancer relies on histopathological evalution of tissue specimen. However, extensive knowledge of the metabolic biochemistry of tumors can potentially provide important information for accurate diagnosis of lung cancer. High resolution magic-angle spinning NMR spectroscopy has emerged and be widely acknowledged as an excellent tool in investigating tissue metabolism. Moreover, the combination of high resolution magic-angle spinning NMR technique and multivariate data analysis has become an important metabonomics platform for studying the intact biological tissues. This study reported the metabonomic characteristics of 51 lung tissues from 17 patients with lung cancer using the high resolution magic-angle spinning 1H NMR spectroscopy and the multivariate data analysis methods including principal component analysis and orthogonal partial least squares-discriminant analysis. Clear differences among the metabonomic characteristics of lung cancer tissues at various sites were disclosed. Compared with the adjacent noninvolved tissues, the lung cancer tissues had significantly high levels of aspartate, phosphocholine, glycerophosphocholine and lactate but significantly low levels of glucose and valine. Furthermore, significantly positive (or negative) correlations were observed between the levels of some metabolites such as lactate, fatty acids, valine, phosphocholine, and glycerophosphocholine.

Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common malignancy in the world with high morbidity and mortality rate. Identification of novel biomarkers in HCC remains impeded primarily because of the heterogeneity of the disease in clinical presentations as well as the pathophysiological variations derived from underlying conditions such as cirrhosis and steatohepatitis. The aim of this study is to search for potential metabolite biomarkers of human HCC using serum and urine metabolomics approach. Sera and urine samples were collected from patients with HCC (n = 82), benign liver tumor patients (n = 24), and healthy controls (n = 71). Metabolite profiling was performed by gas chromatography time-of-flight mass spectrometry and ultra performance liquid chromatography-quadrupole time of flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. Forty three serum metabolites and 31 urinary metabolites were identified in HCC patients involving several key metabolic pathways such as bile acids, free fatty acids, glycolysis, urea cycle, and methionine metabolism. Differentially expressed metabolites in HCC subjects, such as bile acids, histidine, and inosine are of great statistical significance and high fold changes, which warrant further validation as potential biomarkers for HCC. However, alterations of several bile acids seem to be affected by the condition of liver cirrhosis and hepatitis. Quantitative measurement and comparison of seven bile acids among benign liver tumor patients with liver cirrhosis and hepatitis, HCC patients with liver cirrhosis and hepatitis, HCC patients without liver cirrhosis and hepatitis, and healthy controls revealed that the abnormal levels of glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, and chenodeoxycholic acid are associated with liver cirrhosis and hepatitis. HCC patients with alpha fetoprotein values lower than 20 ng/ml was successfully differentiated from healthy controls with an accuracy of 100% using a panel of metabolite markers. Our work shows that metabolomic profiling approach is a promising screening tool for the diagnosis and stratification of HCC patients.

Heavy doping of H − ion in 12CaO·7Al 2O 3

12CaO·7Al 2O 3 (C12A7, mayenite), which has a nanoscale porous structure that can accommodate extraframework species such as hydride (H −), oxide (O 2−), hydroxide (OH −) ions, and electrons, has been doped with H − ions to investigate its effects as dominant extraframework species. Chemical doping with CaH 2 enables the concentration of H − ions to reach almost the theoretical maximum. The concentration of H − ions is characterized by optical absorption intensity ascribed to photoionization of H − ions, and 1H magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. Persistent electron generation, which is accompanied by the formation of an F + absorption band and electrical conductivity, by irradiation with ultraviolet light at room temperature increases as the H − ion doping increases until it reaches half the theoretical maximum and then decreases as the H − ion concentration increases further. This dependence indicates that both H − and O 2− ions are necessary for the generation of persistent electrons.

A silanol protection mechanism: Understanding the decomposition behavior of surfactants in mesostructured solids

Abstract

Metabolic Profiling Detects Field Effects in Nondysplastic Tissue from Esophageal Cancer Patients

The variable rate of missed cancer in endoscopic biopsies and lack of other biomarkers reduce the effectiveness of surveillance programs in esophageal cancer. Based on the "field cancerization" hypothesis that tumors arise within a transformed field with an altered biochemical phenotype, we sought to test if metabolic profiling could differentiate between histologically normal tissue from individuals with and without esophageal cancer. Thirty-five patients with esophageal adenocarcinoma and 52 age-matched controls participated in the study. Using 1H magic angle spinning-nuclear magnetic resonance spectroscopy of intact tissue, we generated metabolic profiles of tumor tissue, proximal histologically normal mucosa from cancer patients (PHINOM), and proximal histologically normal mucosa from a control group. Using multivariate regression and receiver-operator characteristic analysis, we identified a panel of metabolites discriminating malignant and histologically normal tissues from cancer patients and from that of controls. Whereas 26% and 12% of the spectral profile regions were uniquely discriminating tumor or control tissue, respectively, 5% of the profile exhibited a significant progressive change in signal intensity from controls to PHINOM to tumor. Regions identified were assigned to phosphocholine (PC), glutamate (Glu), myo-inositol, adenosine-containing compounds, uridine-containing compounds, and inosine. In particular, the PC/Glu ratio in histologically normal tissue signified the presence of esophageal cancer (n=123; area under the curve, 0.84; P<0.001). In conclusion, our findings support the hypothesis of the presence of metabonomic field effects in esophageal cancer, even in non-Barrett's segments. This indicates that metabolic profiling of tissue can potentially play a role in the surveillance of cancer by reporting on the phenotypic consequences of field cancerization.

Effect of DMSO on micellization, gelation and drug release profile of Poloxamer 407

The application of many recently developed or approved drugs and pharmaceuticals is seriously hampered by their low solubility in aqueous media. Hence, numerous promising pharmaceutical delivery systems (including novel “smart” systems based on poloxamer gels, which have highly advantageous thermo-reversible characteristics and low toxicity) cannot solubilize required doses of various drugs without additives such as co-solvents or salts. Therefore, we have studied the effects of dimethyl sulphoxide (DMSO) – a commonly used co-solvent during drug development stages – on the micellization, gelation and dissolution properties of aqueous poloxamer solutions. Differential scanning calorimetry and tube inversion experiments clearly showed that DMSO induces reductions in the critical micellization and gelation temperatures of poloxamer systems. In addition, high resolution solid state 1H Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses provided indications of the specific chemical groups in the poloxamer affected by DMSO, and the molecular mechanism involved. The presence of DMSO accelerated dissolution of the pure gel in water and the release of a hydrophobic drug (flufenamic acid) from poloxamer gel, while it reduced the release of a hydrophilic drug (metoprolol tartrate).

Solid-State NMR Reveals the Hydrophobic-Core Location of Poly(amidoamine) Dendrimers in Biomembranes

Poly(amidoamine) (PAMAM) dendrimer nanobiotechnology shows great promise in targeted drug delivery and gene therapy. Because of the involvement of cell membrane lipids with the pharmacological activity of dendrimer nanomedicines, the interactions between dendrimers and lipids are of particular relevance to the pharmaceutical applications of dendrimers. In this study, solid-state NMR was used to obtain a molecular image of the complex of generation-5 (G5) PAMAM dendrimer with the lipid bilayer. Using (1)H radio frequency driven dipolar recoupling (RFDR) and (1)H magic angle spinning (MAS) nuclear Overhauser effect spectroscopy (NOESY) techniques, we show that dendrimers are thermodynamically stable when inserted into zwitterionic lipid bilayers. (14)N and (31)P NMR experiments on static samples and measurements of the mobility of C-H bonds using a 2D proton detected local field protocol under MAS corroborate these results. The localization of dendrimers in the hydrophobic core of lipid bilayers restricts the motion of bilayer lipid tails, with the smaller G5 dendrimer having more of an effect than the larger G7 dendrimer. Fragmentation of the membrane does not occur at low dendrimer concentrations in zwitterionic membranes. Because these results show that the amphipathic dendrimer molecule can be stably incorporated in the interior of the bilayer (as opposed to electrostatic binding at the surface), they are expected to be useful in the design of dendrimer-based nanobiotechnologies.

Influence of Silica Nanoparticles on the Crystallization Behavior of and Proton Relaxation in Cesium Hydrogen Sulfate

The influence of nanoparticulate SiO_2 on the crystallization behavior of CsHSO_4 from aqueous solution has been quantitatively evaluated using powder X-ray diffraction (XRD) and ^1H magic angle spinning nuclear magnetic resonance (NMR) spectroscopy. It is shown that SiO_2 induces amorphization of a portion of CsHSO_4 and crystallization of the otherwise metastable phase II form of CsHSO_4. The fraction of amorphized CsHSO_4 (as determined from an evaluation of the XRD peak intensity) was found to increase from 0% in the absence of SiO_2 to fully amorphized in the presence of 90 mol % (~70 wt %) SiO_2. Within the crystalline portion of the composites, the weight fraction of CsHSO_4 phase III was observed to fall almost monotonically from 100% in the absence of SiO_2 to about 40% in the presence of 70 mol % SiO_2 (from both XRD and NMR analysis). These results suggest a crystallization pathway in which SiO_2 particles incorporate an amorphous coating of CsHSO_(4-)like material and are covered by nanoparticulate CsHSO_(4-II), which coexists with independently nucleated particles of CsHSO_(4-III). In composites with small molar fractions of CsHSO_4, the entirety of the acid salt is consumed in the amorphous region. At high CsHSO_4 content, the extent of amorphization becomes negligible, as does the extent of crystallization in metastable phase II. The phase distribution was found to be stable for over 1 year, indicating the strength of the stabilization effect that SiO_2 has on phase II of CsHSO_4.

1H, 13C and 31P MAS NMR studies of lyophilized brain tumors

1H, 13C and 31P magic angle spinning magnetic resonance spectra (MAS NMR) of lyophilized brain tissue specimens were recorded. Among the 35 cases of brain tumors there were 24 glioblastomas, seven meningiomas and a few other types. 1H NMR measurements were performed with a MAS speed of 33 kHz. The intense CH 3, CH 2 and CH peaks in the 1H spectrum result from fatty acid residues of phospholipids, which are “mobile enough” besides the anhydrous environment. 13C CPMAS spectra revealed the resonances of creatine and guanidine carbons; the high intensity signals arise from carbonyl groups and methylene carbons of lipids. In particular we found a fraction of mobile lipids, characterized by narrow resonances and long T 1 ρ H Overlapped resonances of phospholipids head groups contributed to the peak at 4–7 ppm in the 31P MAS NMR spectra. Our results indicate that 1H and 13C MAS NMR are able to characterize tumor types: differentiate glioblastomas from meningiomas and shed light on tumor biochemical characteristics. However, water soluble metabolites are not observed and macromolecules yield broad overlapped resonances. Generally, lyophilization significantly decreases discriminative potential of NMR analysis.

Solid‐state NMR spectroscopy of Pb‐rich apatite

Pb-containing hydroxylapatite phases synthesized under aqueous conditions were investigated by X-ray diffraction and solid-state nuclear magnetic resonance (NMR) techniques to determine the Pb, Ca distribution. 31P and 1H magic-angle spinning (MAS) NMR results indicate slight shifts of the isotropic chemical shift with increased Ca content and complex lineshapes at compositions with near equal amounts of Ca and Pb. 31P{207Pb} and 1H{207Pb} rotational-echo double resonance (REDOR) results for intermediate compositions show that resolved spectral features cannot be assigned simply in terms of local Ca, Pb configurations or coexisting phases. 207Pb MAS NMR spectra are easily obtained for these materials and contain well-resolved resonances for crystallographically unique A1 and A2 Pb sites. Splitting of the A1 and A2 207Pb resonances for pure hydroxyl-pyromorphite (Pb10(PO4)6(OH)2) compared to natural pyromorphite (Pb5(PO4)3Cl) suggests symmetry reduced from hexagonal. We find that 207Pb{1H} CP/MAS NMR is impractical in Pb-rich hydroxylapatites due to fast 207Pb relaxation.

Hydrogen-containing groups in silica glasses

The structures formed by hydrogen in two types of silica glass are investigated using infrared spectroscopy, 1H magic angle spinning magnetic resonance spectroscopy, and quadrupole mass spectrometry. The results obtained from these investigations show that hydrogen in silica glass can exist in the form of isolated SiOH groups, SiOH groups with hydrogen bonds, pairs of neighboring SiOH groups, SiH groups, physically dissolved molecular hydrogen, and molecular water. The structures containing H atoms in the glass synthesized by oxygen-hydrogen gas-flame hydrolysis of SiCl4 differ from those in the glass produced by melting a silica powder in a hydrogen atmosphere.

Speciation of hydrogen in silica glass by 1H MAS NMR

Abstract The H-bearing species in silica glass melted quartz powder in hydrogen atmosphere have been investigated using high-resolution 1H magicangle spinning nuclear magnetic resonance (1H MAS NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy and quadrupole mass spectrometry. The results show that molecular H2, hydroxyl (OH) groups and hydride (SiH) groups are present in the glass. The physically dissolved molecular H2 is represented by a broad NMR peak with the effects of strong H–H magnetic dipolar interactions. Isolated OH groups and hydrogen bonding OH groups in silica glass have been distinguished by the chemical shift of the 1H NMR spectrum. The influence of E’ center on the 1H MAS NMR spectrum are also analyzed.