Toward understanding the ionization of biomarkers from micrometer particles by bio-aerosol mass spectrometry

The appearance of informative signals in the mass spectra of laser-ablated bio-aerosol particles depends on the effective ionization probabilities (EIP) of individual components during the laser ionization process. This study investigates how bio-aerosol chemical composition governs the EIP values of specific components and the overall features of the spectra from the bio-aerosol mass spectrometry (BAMS). EIP values were determined for a series of amino acid, dipicolinic acid, and peptide aerosol particles to determine what chemical features aid in ionization. The spectra of individual amino acids and dipicolinic acid, as well as mixtures, were examined for extent of fragmentation and the presence of molecular ion dimers, which are indicative of ionization conditions. Standard mixtures yielded information with respect to the significance of secondary ion plume reactions on observed spectra. A greater understanding of how these parameters affect EIP and spectra characteristics of bio-aerosols will aid in the intelligent selection of viable future biomarkers for the identification of bio-terrorism agents.     

Assembly of colloidal particles into microwires using an alternating electric field

We have investigated the dielectrophoretic assembly of colloidal gold, carbon black, and carbon nanotubes into electrical wires. The resulting microwires have diameters less than 1 microm, with lengths ranging from 5 microm to 3 mm. Current-voltage curves for these wires indicate an ohmic response, where the resistance is determined by the type of colloid and by the frequency of the alternating field used to grow the wires. The predicted frequency dependence of dielectrophoresis is confirmed by experiment. Measurements of the threshold voltage for initial wire growth are also presented. These experiments demonstrate that a variety of nanoparticles can be assembled into microwires for sensor applications.     

Synthesis of sterically hindered 1-arylpyrrolidines and 1-arylpiperidines by condensation of primary aromatic amines with cyclic ethers or diols

A variety of 1-($\text{o}$-alkylphenyl)- and 1-($\text{o}$-$\text{o}$'-dialkylphenyl)- pyrrolidines and -piperidines were prepared by the gas phase alumina mediated condensation of tetrahydrofuran (THF), tetrahydropyran (THP) or the corresponding diols with primary aromatic amines in fair to high yield. This methodology can also be used for the synthesis of 1-phenylhexahydroazepine from aniline. A mechanistic interpretation of the catalytic action of alumina is presented.     

A convenient one-pot synthesis of 1,8-naphthyridones

In this paper, we disclose an efficient one-pot procedure for the preparation of substituted 1,8-naphthyridin-4-one analogues. Previous efforts to effect this type of transformation were complicated by the formation of benzene tricarboxylate. Via the use of excess base, the impurity formation was completely inhibited. This allowed for the clean preparation of the desired intermediate and subsequent formation of naphthyridone analogues in a single flask, which could then be crystallized directly from the reaction mixture in good yield and high purity.     

Quantitative measurements of recombinant HIV surface glycoprotein 120 binding to several glycosphingolipids expressed in planar supported lipid bilayers

The interaction of recombinant HIV-1 surface glycoprotein gp120 (rgp120) with natural isolates of lactosylceramide (LacCer), glucosylceramide (GlcCer), and galactosylceramide (GalCer) has been quantitatively measured under equilibrium conditions using total internal reflection fluorescence (TIRF) spectroscopy. The binding affinity (K(a)) of rgp120 to these glycosphingolipids (GSLs), reconstituted at 5 mol % in supported planar lipid bilayers composed of 95 mol % POPC, is ca. 10(6) M(-1) for dissolved rgp120 concentrations greater than 25 nM. In contrast, at concentrations of rgp120 between 0.2 and 15 nM, rgp120 does not bind significantly to LacCer and GlcCer, but has a high affinity for GalCer with a measured K(a) value of 1.6 x 10(9) M(-1). However, protein surface coverage measurements show that this strong binding process accounts for very little of the total protein adsorbed over the entire concentration range studied. At a protein concentration of ca. 20 nM, the surface coverage is only 3% of that achieved at apparent saturation (i.e., when the protein concentration is ca. 220 nM). Thus the "high affinity" binding sites comprise only a small fraction of the total number of binding sites. Several other variables were investigated. Rgp120 binding behavior at membranes doped with alpha-hydroxygalactosylceramide (alpha-GalCer) was very similar to that observed with GalCer, showing that the presence/absence of an alpha-hydroxy moiety does not significantly affect galactosylceramide recognition. Phase segregation of GalCer, which occurs when the mole fraction of this GSL in a POPC bilayer exceeds ca. 0.1, was also investigated and showed no effect on binding affinity at low rgp120 concentrations. To investigate the influence of fatty acid chain length, GSLs with monodisperse C(18) and C(24) chain lengths, both with and without an alpha-hydroxy moiety, were synthesized, and their binding affinity to rgp120 was examined. Relative to the natural isolates (which contain a mixture of chain lengths), minimal differences were observed; thus among the compounds tested, fatty acid chain length does not affect GSL recognition. The results of this work should aid efforts to design anti-HIV-1 agents based on membrane-tethered, carbohydrate-based receptors for rgp120.     

A silanediol inhibitor of the metalloprotease thermolysin: synthesis and comparison with a phosphinic acid inhibitor

A silanediol inhibitor of the metalloprotease thermolysin was prepared for comparison to a known phosphinic acid inhibitor, providing the first comparison of these second-row element based transition-state analogues. Inhibition of thermolysin by the silanediol (K(i) = 41 nM) was comparable to that of the phosphinic acid (K(i) = 10 nM) even though the silanediol is uncharged and thereby lacks the intrinsic Coulombic attraction of the phosphinate anion to the active-site zinc cation. This silanediol protease inhibitor is the least sterically encumbered example prepared to date and, therefore, the most prone toward polymerization. Hydrolysis of a difluorosilane intermediate to the silanediol leads cleanly to a monomeric product.     

The effect of thermal processing on PVC—III. Photo-oxidation of unstabilized PVC

The rate of photo-oxidation of unstabilized PVC is markedly dependent on the severity of the processing operation. In mildly processed PVC, peroxy gel appears to be a very effective photo-initiator whereas in more severely processed polymer, solvent soluble polymer containing polyconjugation, hydroperoxides and carbonyl groups is primarily responsible for photo-initiation. The auto-retardation of photo-oxidation which occurs in all samples is believed to be due to the build-up of a highly absorbing surface layer of degraded polymer.     

Reductive spiroannulation of nitriles with secondary electrophiles

The scope of reductive decyanation and spiroannulation reactions has been expanded to include secondary electrophiles for potentially useful transformations. Secondary phosphates and chlorides, as well as terminal epoxides, cyclize in a stereospecific fashion. Both endo and exo modes of cyclization were observed with terminal epoxides.