Bridging the gap between metabolic profile determination and visualization in neurometabolic disorders: a multivariate analysis of proton magnetic resonance in vivo spectra

The purpose of this work was to check the degree of overlap between rare inborn errors of metabolism and other neurological disorders using principal component analysis of proton magnetic resonance spectroscopy (¹H MRS) in vivo data. We examined 60 patients (median age of 22 months). Fourteen of them were diagnosed with neurometabolic disorders (three cases of metachromatic leukodystrophy, two cases of Canavan disease, two cases of megalencephalic leukoencephalopathy with subcortical cysts, three cases of mitochondrial cytopathy, one case of nonketotic hyperglycinemia, one case of globoid leukodystrophy, one case of congenital disorders of glycosylation, and one case of ethylmalonic encephalopathy). The remaining 46 patients were diagnosed with epilepsy, cerebral palsy, and developmental delay. Results obtained from principal component analysis of complete unresolved ¹H MRS in vivo spectra were interpreted parallelly with LCModel‐derived metabolite levels. The main attention was paid to the following metabolites: N‐acetylaspartate, glutamate + glutamine, creatine, choline, myo‐inositol signal with an uncertain contribution of glycine, and glucose. ¹H MRS in vivo coupled with multivariate analysis is an efficient tool in visualization of metabolic abnormalities in several inborn errors of metabolism (metachromatic leukodystrophy, globoid leukodystrophy, megalencephalic leukoencephalopathy with subcortical cysts, and Canavan disease). Copyright © 2013 John Wiley & Sons, Ltd.     

Insights into the elimination mechanisms employed for the degradation of different hexachlorocyclohexane isomers using kinetic isotope effects and docking studies

Modern DFT functional as well as the continuum solvation model have been applied in order to theoretically predict carbon, chlorine and hydrogen kinetic isotope effects (KIEs) during aerobic degradation of four hexachlorocyclohexane isomers (α, β, δ and γ). A small model of the hexachlorocyclohexane dehydrochlorinase (LinA) active site comprising its catalytic dyad has been constructed based on the receptor–ligand complexes suggested by docking studies and compared to the respective reaction modeled in aqueous solution. In‐depth analysis of chlorine and hydrogen KIEs patterns clearly indicates different transition states in aqueous solution and in the model mimicking the protein active site. Although all isomers seem to undergo a concerted E2 mechanism, the contribution of proton transfer and carbon–chlorine leaving group bond stretch in the transition states differs for the different isomers giving rise to totally different magnitudes of predicted isotope effects. Copyright © 2013 John Wiley & Sons, Ltd.     

Influence of the diol structure on the Lewis acidity of phenylboronates

A series of cyclic esters of pentafluorophenylboronic acid have been obtained and their Lewis acidity evaluated experimentally by a modified Gutmann method. The results based on ³¹P NMR measurements were compared with those determined by quantum mechanical calculations at the DFT‐VSXC/pcS‐2 level of theory. The differences in Lewis acidity are discussed on the basis of electronic and geometric parameters. The calculations revealed that the complexes of investigated esters with Et₃PO have multiple conformers of a wide range of calculated ³¹P NMR shielding constants. Additionally, a correlation between the calculated O‐B‐O angle of esters and the experimental acceptor number was found. Copyright © 2013 John Wiley & Sons, Ltd.     

Calcification of aortic human valves studied in situ by Raman microimaging: following mineralization from small grains to big deposits

A Raman microimaging‐based approach has been used in the current study to evaluate formation and progression of calcification in situ in human stenotic aortic valves obtained during surgical valve replacement. The capability of the method to visualize distribution of the calcified deposits resulted in structural characterization of deposits in the various phases of development. A high spatial resolution of the method along with the confocal depth profiling enabled to identify extremely small salt inclusions (of ca. 0.5 µm in diameter), formed probably at the very early stage of calcification. Structurally, these inclusions are built from an octacalcium phosphate‐like compound that during grains' growth transforms into tricalcium phosphate, mixed with the salt containing the acidic phosphate groups (HPO₄²⁻) and, finally, into stable B‐type hydroxyapatite that is the only salt present in large‐area calcium salt deposits. Copyright © 2013 John Wiley & Sons, Ltd.     

Hydroxyapatite Obtained via the Wet Precipitation Method and PVP/PVA Matrix as Components of Polymer-Ceramic Composites for Biomedical Applications

The aspect of drug delivery is significant in many biomedical subareas including tissue engineering. Many studies are being performed to develop composites with application potential for bone tissue regeneration which at the same provide adequate conditions for osteointegration and deliver the active substance conducive to the healing process. Hydroxyapatite shows a great potential in this field due to its osteoinductive and osteoconductive properties. In the paper, hydroxyapatite synthesis via the wet precipitation method and its further use as a ceramic phase of polymer–ceramic composites based on PVP/PVA have been presented. Firstly, the sedimentation rate of hydroxyapatite in PVP solutions has been determined, which allowed us to select a 15% PVP solution (sedimentation rate was 0.0292 mm/min) as adequate for preparation of homogenous reaction mixture treated subsequently with UV radiation. Both FT-IR spectroscopy and EDS analysis allowed us to confirm the presence of both polymer and ceramic phase in composites. Materials containing hydroxyapatite showed corrugated and well-developed surface. Composites exhibited swelling properties (hydroxyapatite reduced this property by 25%) in simulated physiological fluids, which make them useful in drug delivery (swelling proceeds parallel to the drug release). The short synthesis time, possibility of preparation of composites with desired shapes and sizes and determined physicochemical properties make the composites very promising for biomedical purposes.     

A study of the intermolecular interactions of tolmetin/N-acetyl-l-tyrosine ethyl ester complex

The formation of tolmetin/N-acetyl-l-tyrosine ethyl ester (ATEE) complex has been reported by means of both theoretical and experimental studies, including quantum mechanical calculations as well as UV–vis absorption, fluorescence and time-resolved spectroscopy measurements. It has been found that the fluorescence of ATEE is quenched due to the formation of a non-fluorescent complex between ATEE and tolmetin in the ground state. The geometrical parameters of ATEE/tolmetin complex have been determined with the use of the DFT method applying the B3LYP correlation-exchange functional and 6-31G(d) basis set. The results of experiments indicated the static ATEE quenching by tolmetin. Additionally, the experimental and theoretically predicted Gibbs free energy of complexation has been calculated.     

Zinc(II) and cadmium(II) complexes with <Emphasis Type="Italic">o</Emphasis>-hydroxybenzoic acid or <Emphasis Type="Italic">o</Emphasis>-aminobenzoic acid and 2-methylimidazole

Mixed complexes of the type: Zn(Hsal)₂(2-MeHim)₂, Zn(Han)₂(2-MeHim)₂, Cd(Hsal)₂(2-MeHim)₂, Cd(Han)₂(2-MeHim)₂, where Hsal=OHC₆H₄COO⁻, Han=NH₂C₆H₄COO⁻, 2-MeHim=2-methylimidazol) have been synthesized and characterized by IR spectroscopic and X-ray diffraction studies. Single-crystal X-ray structure of Cd(Hsal)₂(2-MeHim)₂ has been obtained. Thermal behaviour of the compounds was investigated by thermal analysis (TG, DTG, DTA). A coupled TG-MS system was used to analyse the principal volatile products of complexes. Thermal decomposition pathways have been postulated.     

Adsorption of Cu(II), Cd(II), Pb(II), Cr(VI) by double hydroxides on the basis of Al oxide and Zr, Sn, and Ti oxides

It was studied the equilibrium adsorption and adsorption kinetics of Cu(II), Cd(II), Pb(II), and Cr(VI) by composite hydroxides formed by Me _x O _y · nH₂O and Me_0.4–0.7Al_0.6–0.3O _y · nH₂O, where Me = Zr, Sn and Ti. It was estimated the values of the diffusion coefficients of adsorbed ions Cu(II) and Cr(VI) from kinetic values. It was established that the estimated diffusion coefficients of adsorbed ions Cu(II) are in the range 0.4 × 10⁻¹²–2.5 × 10⁻¹² m²/s for individual hydroxides and 1.2 × 10⁻¹²–2.8 × 10⁻¹² m²/s for double hydroxides. The obtained values of diffusion coefficients Cr (VI) for double hydroxides are 0.1 × 10⁻¹⁰–0.4 × 10⁻¹⁰ m²/s.     

Densitometric HPTLC Method for Analysis of Triterpenoids in the Leaves of Jovibarba sobolifera (Sims.) Opiz (Hen and Chickens Houseleek)

JPC – Journal of Planar Chromatography – Modern TLC - High performance thin-layer chromatography (HPTLC) combined with densitometry has been used for analysis of the triterpenoid...