Quantification of β‐aminopropionitrile,an inhibitor of lysyl oxidase activity,in plasma and tumor of mice by liquid chromatography tandem mass spectrometry

Lysyl oxidase enzymes are reported to be involved in patho‐physiological process such as tumorigenesis. β‐Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase activity, suggesting a potentially useful therapeutic of interest in oncology. This paper describes the first assay concerning the quantification of BAPN by mass spectrometry. A high‐performance liquid chromatography tandem mass spectrometry (LC‐MS/MS) assay was developed for the quantification of BAPN in plasma and tumor of mice. This method combines dansyl chloride (Dns) derivatization and extraction using a solid‐phase extraction Oasis^© Max column. Deuterated BAPN was used as internal standard (IS). Separation was achieved using an C₁₈ column HypersylGold, (ThermoElectron), 3.0 µm (100 × 2.1 mm i.d.). Gradient elution with water containing 0.1% acetic acid (A) and acetonitrile containing 0.1% acetic acid (B) was applied. Detection was performed with an electrospray ionization interface operating in negative ion mode. Selected reaction monitoring was used with ion transitions m/z 302 → 249 for BAPN–Dns and m/z 306 → 250 for the IS. The method was fully validated in plasma and was linear and sensitive in the range of 10–500 ng/mL. The lower limit of quantification in plasma was 2.5 ng/mL. This validated assay was successfully applied to a kinetic study of BAPN in mouse plasma and demonstrates that BAPN reaches the tumoral tissue. Copyright © 2014 John Wiley & Sons, Ltd.     

Unsymmetric pyrrole, thiophene, and furan-conjugated comonomers prepared using azomethine connections: potential new monomers for alternating homocoupled products

Unsymmetric comonomers consisting of thiophene, pyrrole, and furan heterocycles were prepared using azomethine bonds. Photophysical investigation of the novel pi-donor-donor-donor segmented compounds revealed that their singlet excited state is only partially deactivated by internal conversion unlike their all-thiophene azomethine analogues. Temperature-dependent steady-state and time-resolved emission studies demonstrated that the unsymmetric compounds deactivated efficiently their singlet excited state by intersystem crossing to populate the triplet manifold. This lower energy state is rapidly deactivated by nonradiative self-quenching. The comonomers and their anodically prepared conjugated homocoupled products are both electrochemically active, resulting in new compounds that can be mutually oxidized and reduced. Meanwhile, the oxidation potentials of the coupled products are shifted by up to 400 mV to more cathodic potentials relative to their corresponding comonomers, confirming their increased degree of conjugation.     

Self-sorting dimerization of tetraurea calix[4]arenes

Calix[4]arenes substituted by four urea functions are self-complementary molecules that spontaneously combine in apolar solvents in the presence of an ammonium salt to form dimeric capsules held together by a belt of hydrogen bonds. In the presence of tetraethylammonium salts, the Et4N+ cation is included as a guest. The sorting between dimeric capsules formed in a mixture of calix[4]arenes directly depends on the steric crowding of the substituents grafted on the urea groups whether aromatic derivatives or aliphatic chains linking urea functions in mono-, di-, or tetraloop structures. Simple rules allow one to anticipate which capsules will be exclusively formed when calix[4]arenes are mixed in different proportions. The stabilization of the dimeric structures by hydrogen bonds is thwarted by the overlaps of aliphatic loops and/or by bulky groups that cannot pass through these loops. Despite the structural similarity of the calixarenes, the exclusive formation of dimers of well-defined compositions and clear titration breaks are observed by electrospray mass spectrometry. This technique yields reliable information on stoichiometries and composition despite measurements in the gas phase rather than in solution and it does not suffer from excessive peak overlaps in contrast with NMR.     

Affinity assays for detection of cellular communication and biomarkers

The biological events occurring in the body are complex and challenging to decode. The expression, production, secretion and interaction of proteins, peptides and small molecules often occur in a fast manner and at low concentrations. Methods used to quantify these events must be rapid, selective, sensitive and robust. In recent years, new variations of affinity methodologies have been developed to facilitate quantitation of these biomolecules. This review will focus on selected affinity techniques that have described multi-analyte measurement, high sensitivity techniques, or the application of new affinity reagents applied to conventional technologies to measure analytes involved in cell communication and biomarkers produced in specific disease states.     

Combination of sorption properties of polydimethylsiloxane and solid‐phase extraction sorbents in a single composite material for the passive sampling of polar and apolar pesticides in water

Passive sampling techniques have been developed as an alternative method for in situ integrative monitoring of trace levels of neutral pesticides in environmental waters. The objective of this work was to develop a new receiving phase for pesticides with a wide range of polarities in a single step. We describe the development of three new composite silicone rubbers, combining polydimethylsiloxane mechanical and sorption properties with solid‐phase extraction sorbents, prepared as a receiving phase for passive sampling. A composite silicone rubber composed of polydimethylsiloxane/poly(divinylbenzene‐co‐N‐vinylpyrrolidone) was selected by batch experiments for its high sorption properties for pesticides with octanol‐water partition coefficients ranging from 2.3 to 5.5. We named this composite material “Polar/Apolar Composite Silicone Rubber”. A structural study by scanning electron microscopy confirmed the homogeneous dispersion of the sorbent particles and the encapsulation of particles within the polydimethylsiloxane matrix. We also demonstrate that this composite material is resistant to common solvents used for the back‐extraction of analytes and has a maximal resistance temperature of 350°C. Therefore, the characteristics of the “Polar/Apolar Composite Silicone Rubber” meet most of the criteria for use as a receiving phase for the passive sampling of pesticides.     

A disymmetric terpyridine based ligand for the formation of luminescent di-aquo lanthanide complexes

The synthesis of ligand H3 based on a disymmetrically substituted terpyridine core functionalised by a carboxylic acid in the 6-position and a bis(carboxymethyl)aminomethyl function in the 6'-position is described. The coordination behaviour of this heptadentate (4N/3O) ligand with lanthanide cations (Ln=Eu, Gd and Tb) was studied in solution showing the formation of complexes with [Ln] stoichiometry. Complexes with general formula [Ln(H2O)2] were isolated from neutral water solutions containing equimolar amounts of cations and ligands, and the complexes were characterized in the solid state (elemental analysis, IR) and in solution (mass spectrometry). The photo-physical properties of the luminescent complexes of Eu and Tb were studied in water solution by means of absorption, steady state and time-resolved emission spectroscopies. Evolution of the luminescence lifetimes of the Eu and Tb complexes in H2O and D2O reveals the presence of two water molecules coordinated in the first coordination sphere of the cations. Despite this important hydration number, the overall luminescence quantum yields of the complexes remained elevated, especially in the case of Tb (Phi=22.0 and 6.5% respectively for Tb and Eu). Upon crystallisation the Gd complex formed dimeric species in which two gadolinium atoms are each heptacoordinated by one ligand, the coordination sphere being completed by a single water molecule and a bridging carboxylate function, pointing to different behaviours in the solid and liquid states.     

Multiple-frequency EPR spectra of two aqueous Gd3+ polyamino polypyridine carboxylate complexes: a study of high field effects

In the search for highly efficient magnetic resonance imaging contrast agents, polyamino polypyridine carboxylate complexes of Gd3+ have shown unusual properties with both very rapid and very slow electron spin relaxation in solution observed by electron paramagnetic resonance. Since the relationship between the molecular structure and the electron spin properties remains quite obscure at this point, detailed studies of such complexes may offer useful clues for the design of Gd3+ compounds with tailored electronic features. Furthermore, the availability of very high-frequency EPR spectrometers based on quasi-optical components provides us with an opportunity to test the existing relaxation theories at increasingly high magnetic fields and observation frequencies. We present a detailed EPR study of two gadolinium polyamino polypyridine carboxylate complexes, [Gd(tpaen)]- and [Gd(bpatcn)(H2O)], in liquid aqueous solutions at multiple temperatures and frequencies between 9.5 and 325 GHz. We analyze the results using the model of random zero-field splitting modulations through Brownian rotation and molecular deformations. We consider the effect of concentration on the line width, as well as the possible existence of an additional g-tensor modulation relaxation mechanism and its possible impact on future experiments. We use (17)O NMR to characterize the water exchange rate on [Gd(bpatcn)(H2O)] and find it to be slow (approximately 0.6 x 10(6) s-1).     

Carbenoid Pathways in Copper‐Catalyzed Intramolecular Cyclopropanations of Phenyliodonium Ylides

The enantioselectivity of the copper‐catalyzed intramolecular cyclopropanation of allyl diazomalonates and the corresponding phenyliodonium ylides was investigated with a series of chiral, non‐racemic ligands. The reaction of 6b in the presence of the bis[dihydrooxazole] ligand Xa in refluxing 1,2‐dichloroethane proceeded to 8b with an enantiomer excess (ee) of up to 72% under optimized conditions. In contrast, 8b resulting from reaction of ylide 7b with the same ligand, but in CH₂Cl₂ at 0°, had an ee of only 30%. With other ligands, diazomalonate 6b reacted with a lower enantioselectivity than ylide 7b , however. The intramolecular cyclopropanation of the acetoacetate‐derived phenyliodonium ylide 15b afforded 16b with 68% ee with ligand Xa , but the corresponding diazo compound was unreactive when exposed to chiral copper catalysts. The observation of asymmetric induction in the Cu‐catalyzed reactions of the ylides 7 and 15 is consistent with a carbenoid mechanism; however, the discrepancy of the enantioselectivities observed between diazomalonate 6b and ylide 7b suggests a competing unselective pathway for cyclopropanation outside of the coordination sphere of copper.     

Spiro[4.4]nonatetraene and its Positive and Negative Radical Ions: Molectronic Structure Investigations

The electronic structure of spiro[4.4]nonatetraene 1 as well as that of its radical anion and cation were studied by different spectroscopies. The electron‐energy‐loss spectrum in the gas phase revealed the lowest triplet state at 2.98 eV and a group of three overlapping triplet states in the 4.5 – 5.0 eV range, as well as a number of valence and Rydberg singlet excited states. Electron‐impact excitation functions of pure vibrational and triplet states identified various states of the negative ion, in particular the ground state with an attachment energy of 0.8 eV, an excited state corresponding to a temporary electron attachment to the 2b₁ MO at an attachment energy of 2.7 eV, and a core excited state at 4.0 eV. Electronic‐absorption spectroscopy in cryogenic matrices revealed several states of the positive ion, in particular a richly structured first band at 1.27 eV, and the first electronic transition of the radical anion. Vibrations of the ground state of the cation were probed by IR spectroscopy in a cryogenic matrix. The results are discussed on the basis of density‐functional and CASSCF/CASPT2 quantum‐chemical calculations. In their various forms, the calculations successfully rationalized the triplet and the singlet (valence and Rydberg) excitation energies of the neutral molecule, the excitation energies of the radical cation, its IR spectrum, the vibrations excited in the first electronic absorption band, and the energies of the ground and the first excited states of the anion. The difference of the anion excitation energies in the gas and condensed phases was rationalized by a calculation of the Jahn‐Teller distortion of the anion ground state. Contrary to expectations based on a single‐configuration model for the electronic states of 1 , it is found that the gap between the first two excited states is different in the singlet and the triplet manifold. This finding can be traced to the different importance of configuration interaction in the two multiplicity manifolds.     

New waterborne epoxy coatings based on cellulose nanofillers

New nanocomposites based on a waterborne epoxy emulsion and a suspension of cellulose crystallites were prepared by film casting in order to obtain coatings displaying both flexibility and stiffness. Tunicin cellulose whiskers are attractive reinforcing fillers due to their high aspect ratio, large interface area, and, significant mechanical properties). Typical processing problems for this type of composite are related to high viscosity values of filled polymers in the in the molten state, the incompatibility between hydrophobic matrices and hydrophilic cellulose and the formation of hydrogen bonds between cellulose of this type of natural fibres in an epoxy matrix. The aim of this work is to solve some of the problems above mentioned by selecting the nature of the components used for coating synthesis film processing. The dynamic mechanical properties display an important improvement of the composite modulus in the rubbery state of the matrix at low concentrations of fillers, which can not be expected other cellulose based fibers.