A new bis(3-hydroxy-4-pyridinone)-IDA derivative as a potential therapeutic chelating agent. Synthesis, metal-complexation and biological assays

A new bis(3-hydroxy-4-pyridinone) derivative of iminodiacetic acid, imino-bis(acetyl(1-(3'-aminopropyl)-3-hydroxy-2-methyl-4-pyridinone)), IDAPr(3,4-HP)(2), has been prepared and studied in its interaction with a set of hard metal ions. This tetradentate ligand presents a much higher chelating efficiency for trivalent hard metal ions (Fe, Ga, Al) than the monodentate derivative Deferriprone, namely at the diluted conditions prevailing in physiological conditions and at low clinical doses. A similar behaviour was also observed for the complexation with Zn(II) but at a significantly lower extent. This compound presents a moderate hydrophilic character at physiological pH (logD=-1.72). In vivo assays showed much more rapid clearance of (67)Ga from most tissues of metal-loaded mice than the drug Deferriprone and the radioactivity excretion occurs mostly through the kidneys. Therefore, results from in vitro and in vivo studies indicated good perspectives for this compound to be a potential decorporating agent for hard metal ions in overload situations without depletion of essential metal ions such as zinc.     

Molecular properties of hemicelluloses located in the surface and inner layers of hardwood and softwood pulps

The molecular properties of hemicelluloses located in the surface and inner layers of fibers present in hardwood and softwood pulps, together with the effects of different bleaching processes on these properties, have been investigated in this study. In order to separate the hemicelluloses located in these two layers, fibers were subjected to mechanical peeling and then separated by filtration into surface (filtrate) and inner layer materials. The materials thus obtained were characterized with respect to their polysaccharide compositions and uronic acid contents. The molar mass parameters of the hemicelluloses (extracted by alkali) were determined by employing size-exclusion chromatography in combination with off-line MALDI mass spectrometry. For all of the pulps examined, the relative content of xylan was found to be greater in the surface layer of the fiber than in the corresponding inner layer. The xylan polymers of the surface layer exhibited higher molar masses and lower frequencies of uronic acid side groups than did the xylans in the inner fiber layer. In connection with ozone treatment, hexenuronic acid residues in the surface layer xylan were removed to a greater extent than in the case of the inner layers, indicating a gradient for the reaction with ozone across the fiber wall. The xylan polymer remaining on the surface of the softwood pulps after completion of the chlorine dioxide bleaching process was predominantly uncharged.     

Di-2-pyridylmethylamine-based palladium complexes as new catalysts for Heck,Suzuki, and Sonogashira reactions in organic and aqueous solvents

A new palladium-dipyridylmethylamine complex is an excellent catalyst for C-C bond-forming processes such as the Heck, Suzuki, and Sonogashira reactions in organic and aqueous solvents under homogeneous conditions. [reaction: see text]     

Mechanistic Insights into the Pd‐Catalyzed Direct Amination of Allyl Alcohols: Evidence for an Outer‐Sphere Mechanism Involving a Palladium Hydride Intermediate

The mechanism of direct amination of allyl alcohol by a palladium triphenylphosphite complex has been explored. Labelling studies show that the reaction proceeds through a π‐allylpalladium intermediate. A second‐order dependence of reaction rate on allyl alcohol concentration was observed. Kinetic isotope effect studies and ESI‐MS studies are in agreement with a reaction proceeding through a palladium hydride intermediate in which both O–H bond and C–O bond cleavages are involved in rate‐determining steps. A stereochemical study supports an outer‐sphere nucleophilic attack of the π‐allylpalladium intermediate giving complete chiral transfer from starting material to product.     

Strategies for differentiation of isobaric flavonoids using liquid chromatography coupled to electrospray ionization mass spectrometry

Flavonoids are a class of secondary plant metabolites existing in great variety in nature. Due to this variety, identification can be difficult, especially as overlapping compounds in both chromatographic separations and mass spectrometric detection are common. Methods for distinguishing isobaric flavonoids using MS² and MS³ have been developed. Chromatographic separation of various plant extracts was done with RP‐HPLC and detected with positive ESI‐MS operated in information‐dependent acquisition (IDA) mode. Two methods for the determination of flavonoid identity and substitution pattern, both featuring IDA criteria, were used together with the HPLC equipment. A third method where the collision energy was ramped utilized direct infusion. With the developed strategies, it is possible to differentiate between many isobaric flavonoids. Various classes of flavonoids were found in all of the plant extracts, in the red onion extract 45 components were detected and for 29 of them the aglycone was characterized, while the substituents were tentatively identified for 31 of them. For the strawberry extract, those numbers were 66, 30 and 60, and for the cherry extract 99, 56 and 71. The great variety of flavonoids, several of them isobaric, found in each of the extracts highlights the need for reliable methods for flavonoid characterization. Methods capable of differentiating between most of the isobars analyzed have been developed. Copyright © 2014 John Wiley & Sons, Ltd.     

Use of INAA and ICP-MS for the assessment of trace element mass fractions in adult and geriatric prostate

The variation with age of the mass fraction of 54 trace elements (Ag, Al, As, Au, B, Be, Bi, Br, Cd, Ce, Co, Cr, Cs, Dy, Er, Eu, Fe, Ga, Gd, Hf, Hg, Ho, Ir, La, Li, Lu, Mn, Mo, Nb, Nd, Ni, Pb, Pd, Pr, Pt, Rb, Re, Sb, Sc, Se, Sm, Sn, Ta, Tb, Te, Th, Ti, Tl, Tm, U, Y, Yb, Zn, and Zr) in intact nonhyperplastic prostate of 65 healthy 21–87 year old males was investigated by instrumental neutron activation analysis with high resolution spectrometry of long-lived radionuclides and inductively coupled plasma mass spectrometry. This work revealed that there is a significant tendency for an increase in Bi, Cd, Co, Fe, Hg, Sc, Sn, Th, U, and Zn (p < 0.0014) mass fraction in normal prostate from age 21 years to the sixth decade. In the sixth to ninth decades the mass fractions of almost all chemical elements investigated in nonhyperplastic prostates were maintained at approximately stable levels. Our finding of correlation between pairs of prostatic chemical element mass fractions indicates that there is a great disturbance of prostatic chemical element relationships with increasing age.     

A Rapidly Reversible Chemical Dimerizer System to Study Lipid Signaling in Living Cells

Chemical dimerizers are powerful tools for non‐invasive manipulation of enzyme activities in intact cells. Here we introduce the first rapidly reversible small‐molecule‐based dimerization system and demonstrate a sufficiently fast switch‐off to determine kinetics of lipid metabolizing enzymes in living cells. We applied this new method to induce and stop phosphatidylinositol 3‐kinase (PI3K) activity, allowing us to quantitatively measure the turnover of phosphatidylinositol 3,4,5‐trisphosphate (PIP₃) and its downstream effectors by confocal fluorescence microscopy as well as standard biochemical methods.     

Determination of oxygenated and native polycyclic aromatic hydrocarbons in urban dust and diesel particulate matter standard reference materials using pressurized liquid extraction and LC–GC/MS

The objective of this study was to develop a novel analytical chemistry method, comprised of a coupled high-performance liquid chromatography–gas chromatography/mass spectrometry system (LC–GC/MS) with low detection limits and high selectivity, for the identification and determination of oxygenated polycyclic aromatic hydrocarbons (OPAHs) and polycyclic aromatic hydrocarbons (PAHs) in urban air and diesel particulate matter. The linear range of the four OPAHs, which include 9,10-anthraquinone, 4H-cyclopenta[def]phenanthrene-4-one, benzanthrone, and 7,12-benz[a]anthraquinone, was 0.7 pg–43.3 ng with limits of detection (LODs) and limits of quantification (LOQs) on the order of 0.2–0.8 and 0.7–1.3 pg, respectively. The LODs in this study are generally lower than values reported in the literature, which can be explained by using large-volume injection. The recoveries of the OPAHs spiked onto glass fiber filters using two different pressurized liquid extraction (PLE) methods were in the ranges of 84–107 and 67–110 %, respectively. The analytical protocols were validated using the following National Institute of Standards and Technology standard reference materials: SRM 1649a (Urban Dust), SRM 1650b (Diesel Particulate Matter), and SRM 2975 (Diesel Particulate Matter, Industrial Forklift). The measured mass fractions of the OPAHs in the standard reference materials (SRMs) in this present study are higher than the values from the literature, except for benzanthrone in SRM 1649a (Urban Dust). In addition to the OPAHs, 44 PAHs could be detected and quantified from the same particulate extract used in this protocol. Using data from the literature and applying a two-sided t test at the 5 % level using Bonferroni correction, significant differences were found between the tested PLE methods for individual PAHs. However, the measured mass fractions of the PAHs were comparable, similar to, or higher than those previously reported in the literature.     

Immobilization of Distinctly Capped CdTe Quantum Dots onto Porous Aminated Solid Supports

Immobilization of quantum dots (QDs) onto solid supports could improve their applicability in the development of sensing platforms and solid‐phase reactors by allowing the implementation of reusable surfaces and the execution of repetitive procedures. As the reactivity of QDs relies mostly on their surface chemistry, immobilization could also limit the disruption of solution stability that could prevent stable measurements. Herein, distinct strategies to immobilize QDs onto porous aminated supports, such as physical adsorption and the establishment of chemical linking, were evaluated. This work explores the influence of QD capping and size, concentration, pH, and contact time between the support and the QDs. Maximum QD retention was obtained for physical adsorption assays. Freundlich and Langmuir isotherms were used to analyze the equilibrium data. Gibbs free energy, enthalpy, and entropy were calculated and the stability of immobilized QDs was confirmed.