Solid state NMR investigation of intact human bone quality: balancing issues and insight into the structure at the organic-mineral interface

Age-related bone fragility fractures present a significant problem for public health. Measures of bone quality are increasingly recognized to complement the conventional bone mineral density (BMD) based assessment of fracture risk. The ability to probe and understand bone quality at the molecular level is desirable in order to unravel how the structure of organic matrix and its association with mineral contribute to the overall mechanical properties. The (13)C{(31)P} REDOR MAS NMR (Rotational Echo Double Resonance Magic Angle Spinning Nuclear Magnetic Resonance) technique is uniquely suited for the study of the structure of the organic-mineral interface in bone. For the first time, we have applied it successfully to analyze the structure of intact (non-powdered) human cortical bone samples, from young healthy and old osteoporotic donors. Loading problems associated with the rapid rotation of intact bone were solved using a Finite Element Analysis (FEA) approach, and a method allowing osteoporotic samples to be balanced and spun reproducibly is described. REDOR NMR parameters were set to allow insight into the arrangement of the amino acids at the mineral interface to be accessed, and SVD (Singular Value Decomposition) was applied to enhance the signal to noise ratio and enable a better analysis of the data. From the REDOR data, it was found that carbon atoms belonging to citrate/glucosaminoglycans (GAGs) are closest to the mineral surface regardless of age or site. In contrast, the arrangement of the collagen backbone at the interface varied with site and age. The relative proximity of two of the main amino acids in bone matrix proteins, hydroxyproline and alanine, with respect to the mineral phase was analyzed in more detail, and discussed in view of glycation measurements which were carried out on the tissues. Overall, this work shows that the (13)C{(31)P} REDOR NMR approach could be used as a complementary technique to assess a novel aspect of bone quality, the organic-mineral interface structure.     

Cyclisation of 1,2-dioxines containing tethered hydroxyl and carboxylic acid functionality: synthesis of tetrahydrofurans and dihydrofuran-2(3H)-ones

Herein we outline cyclisations of tethered hydroxyl and carboxylic acid moieties onto the olefinic motif of 1,2-dioxines to generate tetrahydrofurans and dihydrofuran-2(3H)-ones, whilst maintaining the peroxide linkage intact. This work demonstrates the first examples of intramolecular cyclisation of tethered hydroxyl groupings onto 1,2-dioxines generating functionalised THFs in a highly stereoselective manner and includes improved methods for previously reported carboxylic acid tether cyclisations. Additionally, improved methods for the oxidation of 1,2-dioxines containing tethered alcohols to furnish tethered carboxylic acids are also detailed. Subsequent reduction of the peroxide linkage enables the generation of functionalised tetrahydrofurans and dihydrofuran-2(3H)-ones, which are useful building blocks for the construction of natural products.     

The number of edges of radius-invariant graphs

The eccentricity e(υ) of vertex υ is defined as a distance to a farthest vertex from υ. The radius of a graph G is defined as r(G) = {e(u)}. We consider properties of unchanging the radius of a graph under two different situations: deleting an arbitrary edge and deleting an arbitrary vertex. This paper gives the upper bounds for the number of edges in such graphs. Supported by VEGA grant No. 1/0084/08.     

An oscillation criterion for discrete trigonometric systems

In this paper, we investigate oscillation properties of discrete trigonometric systems whose coefficients matrices are simultaneously symplectic and orthogonal. The main result generalizes a necessary and sufficient condition of non-oscillation of trigonometric systems proved by M. Bohner and O. Do?lý (J. Differential Equations 163 (2000), pp. 113–129) in the case when the block in the upper right corner of the coefficient matrix is symmetric and positive definite. Now, we present this oscillation criterion for an arbitrary trigonometric system. The obtained results are applied to formulate a necessary and sufficient condition for non-oscillation of even-order Sturm–Liouville difference equations.     

Metabolic fingerprinting based on high-resolution tandem mass spectrometry: a reliable tool for wine authentication?

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (MS) and an alternative technology represented by direct analysis in real time coupled with quadrupole time-of-flight MS were investigated for metabolic fingerprinting of 343 red and white wine samples. Direct injection of pure wine and an extraction procedure optimized for isolation of polyphenols were used to compare different analytical and data handling strategies. After data processing and data pretreatment, principal component analysis was initially used to explore the data structure. Initially, the unsupervised models revealed a notable clustering according to the grape varieties, and therefore supervised orthogonal partial least squares discriminant analysis models were created and validated for separation of red and white wines according to the grape variety. The validated orthogonal partial least squares discriminant analysis models based on data (ions) recorded in positive ionization mode were able to classify correctly 95 % of samples. In parallel, authentication parameters, such as origin and vintage, were evaluated, and they are discussed. A tentative identification of markers was performed using accurate mass measurement of MS and MS/MS spectra, different software packages and different online libraries. In this way, different flavonol glucosides and polyphenols were identified as wine markers according to the grape varieties.     

Syntheses,structures and properties of isonicotinamidium,thionicotinamidium, 2- and 3-(hydroxymethyl)pyridinium nitrates

New salts containing cations of selected pyridine derivatives of the composition [pyH]NO₃, where py is 2-pyridylmethanol (2-(hydroxymethyl)pyridine, 2pm), 3-pyridylmethanol (3-(hydroxymethyl) pyridine, 3pm), isonicotinamide (4-(aminocarbonyl)-pyridine, inia) and thionicotinamide (4-(aminothiocarbonyl)pyridine, tnia) were synthesised using two methods. By the first method, the above salts were obtained from reaction mixtures prepared from Fe(NO₃)₃ · 9H₂O and the appropriate pyridine derivative py in ethanol without the addition of acids. The protons required for protonation of the given pyridine derivatives are formed by the protolytic reaction of [Fe(H₂O)₆]³⁺, which acts as a cationic Brønstedt acid. These cations are present in the solid state of Fe(NO₃)₃ · 9H₂O as well as in its solutions. Under the second procedure, the salts were prepared by a direct reaction of the selected pyridine derivative py with a diluted solution of HNO₃. The first method affords crystals with lower yields but the second method produces microcrystals with higher yields. All the compounds were characterised by elemental analysis, infrared and NMR spectroscopic analyses and [3pmH]NO₃ and [2pmH]NO₃ by X-ray structure analysis also. [3pmH]NO₃ crystallises in the monoclinic and [2pmH]NO₃ in the triclinic system.     

Phase transitions of K<Subscript>2</Subscript>TaF<Subscript>7</Subscript> within 680–800°C

Three thermal effects on heating/cooling of K₂TaF₇ in the temperature interval of 680–800°C were investigated by the DSC method. The values determined for the enthalpy change of the individual processes are: Δ_transIIH_m(K₂TaF₇; 703°C) = 1.7(2) kJ mol⁻¹, Δ_transIH_m(K₂TaF₇; 746°C) = 19(1) kJ mol⁻¹ and Δ_transIIIH_m(K₂TaF₇; 771°C) = 13(1) kJ mol⁻¹. The first thermal effect was attributed to a solid-solid phase transition; the second to the incongruent melting of K₂TaF₇ and the third to mixing of two liquids. These findings are supported by in situ neutron powder diffraction experiments performed in the temperature interval of 654–794°C.      

Synthesis of electron energy loss spectra for the quantification of detection limits.

We describe a method for predicting detection limits of minority elements in electron energy loss spectroscopy (EELS), and its implementation as a software package that gives quantitative predictions for user-specified materials and experimental conditions. The method is based on modeling entire energy loss spectra, including shot noise as well as instrumental noise, and taking into account all the relevant experimental parameters. We describe the steps involved in modeling the entire spectrum, from the zero loss up to inner shell edges, and pay particular attention to the contributions to the pre-edge background. The predicted spectra are used to evaluate the signal-to-noise ratios (SNRs) for inner shell edges from user-specified minority elements. The software also predicts the minimum detectable mass (MDM) and minimum mass fraction (MMF). It can be used to ascertain whether an element present at a particular concentration should be detectable for given experimental conditions, and also to quickly and quantitatively explore ways of optimizing the experimental conditions for a particular EELS analytical task. We demonstrate the usefulness of the software by confirming the recent empirical observation of single atom detection using EELS of phosphorus in thin carbon films, and show the effect on the SNR of varying the acquisition parameters. The case of delta-doped semiconductors is also considered as an important example from materials science where low detection limits and high spatial resolution are essential, and the feasibility of such characterization using EELS is assessed.     

Laser ablation generation of cluster ions from concentrated sulfuric and selenic acids

The generation and identification of novel homo- and hetero-polyacid clusters was achieved using a standard matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. The formation of several singly charged species was achieved via the interaction of a laser beam with concentrated sulfuric acid, selenic acid or their mixtures, applied on a graphite microcrucible. A higher yield of the species was observed in the negative detection mode, where sulfuric acid adducts HSO(4) (-) . mH(2)SO(4) (m = 0-3) and HSO(4) (-) . mH(2)SO(4) . SO(3) (m = 1, 2), and selenic acid adducts HSeO(4) (-), HSeO(4) (-) . X (X = SeO(3), H(2)SeO(4), 2SeO(3), H(2)SO(4) . SeO(3)) and NaSeO(4) (-). Y (Y = H(2)SeO(4), H(2)SeO(4). SeO(3), 2H(2)SO(4), H(2)SeO(4) . 2SeO(3), 2H(2)SeO(4) . SeO(3), 3H(2)SeO(4)), were identified. In the mass spectra of the mixture of acids, besides the homo-polyacidic adducts, eleven mixed species containing both sulfuric and selenic acid molecules or ions were identified, of which the heaviest was found to correspond to NaSeO(4) (-) . H(2)SeO(4) . 3SO(3). The stoichiometry of the species was confirmed using isotopic pattern modeling.     

Intracluster stereochemistry in van der Waals complexes: steric effects in ultraviolet photodissociation of state-selected Ar-HOD/H2O

High-resolution IR-UV multiple resonance methods are employed to elucidate the photodissociation dynamics of quantum state-selected Ar-HOD and Ar-H(2)O van der Waals clusters. A single mode pulsed OPO operating in the region of the OH second overtone is used to prepare individual rovibrational states that are selectively photodissociated at specific excimer wavelengths. Subsequent fluorescence excitation of the resulting OH (OD) fragments yields dynamical information on the photofragmentation event and any resulting intracluster collisions. This technique is used to characterize spectroscopically the Pi(1(01)), nu(OH)=3<--Sigma(0(00)), v(OH)=0 overtone band of the Ar-HOD complex with an origin at 10648.27 cm(-1). The effects of Ar complexation on the dissociation dynamics are inferred by comparison of the OD photofragment quantum state distributions resulting from dissociation of single rovibrational states of the complex with those from isolated HOD photodissociation. The important role played by the initial internal state of the complex is demonstrated by comparison of the current Ar-HOD data with previously published results for the Ar-H(2)O Sigma(0(00))[03(-)> state. We interpret the dramatic differences in the dynamics of the two systems as manifestations of the nodal structure of the vibrational state in the parent complex and the way in which it governs the collision probability between the Ar atom and the escaping photofragments.