The synthesis of metallocene-labelled drugs for biological assays

Several drugs (amphetamine, desipramine, nortriptyline, phenobarbital) have been labelled with metallocenic fragments in order to develop a new immunoassay method. The metallocenic fragments are cymantrenic or benchrotrenic derivatives: the linkage between the organic and organometallic moieties has been achieved by reactions between amino and acidic functional groups. All the products (metallohaptens), purified by different chromatography techniques, have been fully characterized by IR and ¹H NMR spectroscopy and their mass spectra.     

Complexes du titane et du zirconium contenant les ligands cyclopentadienyldiphenylphosphine et cyclopentadienylethyldiphenylphosphine: acces a des structures heterobimetalliques

Reactions of Ph₂P(CH₂)_n(C₅H₄)Li, (n = 0, 2), with MCl₄ or CpTiCl₃ (M = Ti, Zr; Cp = η⁵-C₅H₅) form Cl₂M[(η⁵-C₅H₄)(CH₂)_nPPh₂]₂ or Cl₂CpTi[(η⁵-C₅H₄)-(CH₂)₂PPh₂] in good yields. Chemical reduction with Al, or electrochemical reduction of these complexes, under CO, are described. The titanium(IV) and zirconium(IV) derivatives react with metal carbonyls (Mo(CO)₆, Cr(CO)₆, Fe(CO)₅, Mo(CO)₄(C₈H₁₂)) under formation of new heterobimetallic complexes. Reduction with Al of Cl₂CpTi[(η⁵-C₅H₄)(CH₂)₂PPh₂]Mo(CO)₅ under CO results in a new heterobimetallic species containing low valent titanium. Both complexes Cl₂M[(η⁵-C₅H₄)(CH₂)₂PPh₂]₂ (M = Ti, Zr) react with [Rh(μ-Cl)(CO)(C₂H₄)]₂ to yield {RhCl(CO)(Cl₂M[(η⁵-C₅H₄)(CH₂)₂PPh₂]₂)}x, which is assumed to be a dimer, in which the titanium or the zirconium compounds act as bridging diphosphine ligands between the rhodium atoms.     

Estimation of the annual solar UVR exposure dose of infants and small children in tropical Queensland, Australia

The solar ultraviolet radiation (UVR) exposure of infants and small children was measured for 1 week using UVR-sensitive polysulfone film attached to the shoulder and chest of the subjects. For the infant study, shoulder and chest badges received similar exposures, while the 2 1/2-year-olds received higher exposures on the shoulder than on the chest. Also, the 2 1/2-year-olds generally received higher exposures than the infants. The median total daily exposures for both groups were 39 and 92 J/m2. The maximum total daily exposures measured were 640 J/m2 (chest) and 240 J/m2 (shoulder) for the infants and 2060 J/m2 (shoulder) and 840 J/m2 (chest) for the 2 1/2 year-olds. Using this exposure data, monthly and annual exposure doses were calculated for both groups and compared to similar data from the UK. The annual exposure dose for infants is 8.4 kJ/m2 or 84 standard erythemal dose (SED) for both shoulder and chest. The annual exposure dose for 2 1/2 year-old children is 39.4 kJ/m2 or 394 SED for the shoulder and 28.8 kJ/m2 or 288 SED for the chest. Apart from the generally higher annual exposure doses experienced by the infants and 2 1/2 year-old children in Townsville, the main difference to the UK is the almost nonexistent drop in monthly exposure doses between summer and winter in Townsville compared to the UK. In the UK, the winter-month exposure dose is only 0.5% of the summer-month dose. However, in Townsville it is around 40%.     

Inelastic state-to-state scattering of OH (2Pi3/2, J=3/2,f) by HCl

Parity resolved state-to-state cross sections for inelastic scattering of OH (X2Pi) by HCl were measured in a crossed molecular beam experiment at the collision energy of 920 cm(-1). The OH (X2Pi) radicals were prepared in a single quantum state, Omega=3/2, J=3/2, MJ=3/2, f, by means of electrostatic state selection in a hexapole field. The rotational distribution of the scattered OH radicals by HCl was probed by saturated LIF spectroscopy of the 0-0 band of the A 2Sigma+ - X 2Pi transition. Relative state-to-state cross sections were measured for rotational excitations up to J=9/2 within the Omega=3/2 spin-orbit manifold and up to J=7/2 within the Omega=1/2 spin-orbit manifold. A propensity for spin-orbit conserving transitions was found, but no propensity for excitation into a particular Lambda-doublet component of the same rotational state was evident. The data are presented and discussed in comparison with results previously obtained for collisions of OH with CO (Ecoll=450 cm(-1)) and N2 (Ecoll=410 cm(-1)) and with new data we have measured for the OH+CO system at a comparable collision energy (Ecoll=985 cm(-1)). This comparison suggests that the potential energy surface (PES) governing the interaction between OH and HCl is more anisotropic than the PES's governing the intermolecular interaction of OH with CO and N2.     

Substrate and Substrate-Mimetic Chaperone Binding Sites in Human α-Galactosidase A Revealed by Affinity-Mass Spectrometry

Fabry disease (FD) is a rare metabolic disorder of a group of lysosomal storage diseases, caused by deficiency or reduced activity of the enzyme α-galactosidase. Human α-galactosidase A (hαGAL) hydrolyses the terminal α-galactosyl moiety from glycosphingolipids, predominantly globotriaosylceramide (Gb3). Enzyme deficiency leads to incomplete or blocked breakdown and progressive accumulation of Gb3, with detrimental effects on normal organ functions. FD is successfully treated by enzyme replacement therapy (ERT) with purified recombinant hαGAL. An emerging treatment strategy, pharmacologic chaperone therapy (PCT), employs small molecules that can increase and/or reconstitute the activity of lysosomal enzyme trafficking by stabilizing misfolded isoforms. One such chaperone, 1-deoxygalactonojirimycin (DGJ), is a structural galactose analogue currently validated in clinical trials. DGJ is an active-site-chaperone that binds at the same or similar location as galactose; however, the molecular determination of chaperone binding sites in lysosomal enzymes represents a considerable challenge. Here we report the identification of the galactose and DGJ binding sites in recombinant α-galactosidase through a new affinity-mass spectrometry-based approach that employs selective proteolytic digestion of the enzyme–galactose or –inhibitor complex. Binding site peptides identified by mass spectrometry, [39–49], [83–100], and [141–168], contain the essential ligand-contacting amino acids, in agreement with the known X-ray crystal structures. The inhibitory effect of DGJ on galactose recognition was directly characterized through competitive binding experiments and mass spectrometry. The methods successfully employed in this study should have high potential for the characterization of (mutated) enzyme–substrate and –chaperone interactions, and for identifying chaperones without inhibitory effects.

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A Molecular Pillar Approach To Grow Vertical Covalent Organic Framework Nanosheets on Graphene: Hybrid Materials for Energy Storage

Hybrid 2D–2D materials composed of perpendicularly oriented covalent organic frameworks (COFs) and graphene were prepared and tested for energy storage applications. Diboronic acid molecules covalently attached to graphene oxide (GO) were used as nucleation sites for directing vertical growth of COF‐1 nanosheets (v‐COF‐GO). The hybrid material has a forest of COF‐1 nanosheets with a thickness of 3 to 15 nm in edge‐on orientation relative to GO. The reaction performed without molecular pillars resulted in uncontrollable growth of thick COF‐1 platelets parallel to the surface of GO. The v‐COF‐GO was converted into a conductive carbon material preserving the nanostructure of precursor with ultrathin porous carbon nanosheets grafted to graphene in edge‐on orientation. It was demonstrated as a high‐performance electrode material for supercapacitors. The molecular pillar approach can be used for preparation of many other 2D‐2D materials with control of their relative orientation.     

Synthesis and Characterization of Diatomaceous Earth Chemically Modified with γ-Aminopropyltrimethoxysilane

JPC – Journal of Planar Chromatography – Modern TLC - A stationary phase for thin-layer chromatography has been prepared by bonding purified diatomaceous earth (rich in silica) with...     

Synthesis,characterization and X-ray crystal structures of two non-molecular coordination polymers of manganese(II) and copper(II) with <Emphasis Type="Italic">N</Emphasis>-(2-pyridylmethyl)-<Emphasis Type="SmallCaps">l</Emphasis>-alanine and isothiocyanato ligands

The reduced Schiff base, N-(2-pyridylmethyl)-l-alanine (Pyala), has been prepared and used as a ligand for the synthesis of two new non-centrosymmetrical isothiocyanate mixed-ligand coordination polymers, [MnPyalaSCN] _n and [CuPyalaSCN] _n . Pyala and the metal complexes were characterized by physico-chemical and spectroscopic methods. The single-crystal X-ray structures of the complexes reveal both compounds to be non-molecular coordination polymers which crystallize in the orthorhombic system. The ligand acts as a bridge between two metal centres in both compounds, forming two six-membered rings around each Mn atom and two five-membered rings around each Cu centre. The 1D chains are assembled via N–H?O, N–H?S hydrogen bonds and S–S interactions building 3D helical supramolecular networks in both compounds. Packing of the polymers of both compounds along the b-axis gives chiral channels.     

Strategies to Improve the Thermo-Oxidative Stability of Sunflower Oil by Exploiting the Antioxidant Potential of Blueberries Processing Byproducts

This research was conducted in order to establish the effectiveness of two freeze-dried extracts obtained from blueberry processing byproducts resulting from juice manufacturing compared to butylated hydroxytoluene (BHT) in delaying the lipid oxidation of sunflower oil subjected to high-temperature convective heating at 180 °C up to 12 h under simulated frying conditions. The fruits were harvested from spontaneous flora of two regions of Romania, Arieseni (Alba County) and Paltinis (Sibiu County) and the blueberry byproducts extracts (BBE) were noted according to the origin place as ABBE and PBBE. The progress of lipid thermo-oxidation was investigated in terms of peroxide value (PV), p-anisidine value (p-AV), the response of TBA-malondialdehyde interactions assessed by thiobarbituric acid (TBA) method, the total oxidation (TOTOX) value and inhibition of oil oxidation (IO). The recorded data highlighted that BBE exhibit a high inhibitory response on lipid thermo-oxidation. The inhibitory effect was concentration-dependent, thus, the degree of lipid oxidation was in reverse related to the BBE dose. The exposure of the oil samples supplemented with 800 ppm BBE (ABBE, PBBE) to a high-temperature heating for 12 h led to a significant decrease of the assessed indices compared to additives-free sunflower oil sample as follows: PV (46%; 45%), p-AV (21%; 17%), TOTOX (27%; 24%), TBA value (25%; 11%). Regarding the impact of the origin on the potential of BBE to inhibit the lipid oxidative degradation, it was noted that ABBE derived from blueberries grown in a region with a milder climate with moderate precipitations and higher temperatures showed a stronger inhibitory effect on lipid thermo-oxidation than PBBE. A moderate level of 500 ppm BBE inhibited the lipid oxidation similar to 200 ppm BHT. The reported results reveal that BBE represent efficient natural antioxidants that could be successfully applied to improve the thermo-oxidative stability of sunflower oil used in various high-temperature food applications.