High-throughput synthesis of HepDirect prodrugs of nucleoside monophosphates

A high-throughput phosphoramidite method for HepDirect prodrug synthesis was optimized on seven representative nucleosides, adenosine, inosine, guanosine, uridine, cytidine, AICA-riboside, and thymidine, each on a 5 mg scale. The variables optimized included (1) reaction time, (2) reaction temperature, (3) activating agent, (4) solvent, (5) purification method, and (6) stoichiometry. Preparative HPLC with mass-based fraction collection and yield determination from an ELSD standard curve enabled high-throughput. The optimized conditions for the representative nucleosides required 6 mol equiv of phosphoramidite to nucleoside and resulted in an average HPLC determined yield of 31 +/- 14% and HPLC purity of 93 +/- 3%.     

Interpreting ultrafast molecular fragmentation dynamics with ab initio electronic structure calculations

High-level ab initio electronic structure calculations are used to interpret the fragmentation dynamics of CHBr(2)COCF(3), following excitation with an intense ultrafast laser pulse. The potential energy surfaces of the ground and excited cationic states along the dissociative C-CF(3) bond have been calculated using multireference second order perturbation theory methods. The calculations confirm the existence of a charge transfer resonance during the evolution of a dissociative wave packet on the ground state potential energy surface of the molecular cation and yield a detailed picture of the dissociation dynamics observed in earlier work. Comparisons of the ionic spectrum for two similar molecules support a general picture in which molecules are influenced by dynamic resonances in the cation during dissociation.     

Ultrathin layer chromatography on nanostructured thin films

Ultrathin layer chromatography (UTLC) is a relatively new variant of thin layer chromatography, with a 10mum thick monolithic silica sorbent layer that gives faster separations with lower limits of detection and reduced analyte and solvent volumes. We have produced UTLC plates with controllable nanostructure and thickness, and show that the layer separation characteristics depends on the film nanostructure. We also show that layers made with in-plane anisotropic nanostructures will exhibit a decoupling effect, where the analyte spots do not develop in the same direction as the solvent front movement. The added layer morphology and material selection adds a degree of freedom to UTLC, and may have applications in multi-dimensional TLC.     

Electrochemical Oxidation of Metolazone at a Glassy Carbon Electrode

Metolazone is a diuretic agent used in patients with edematous states and/or hypertension. The electrochemical behavior of metolazone on a glassy carbon electrode was investigated using cyclic, differential pulse, and square‐wave voltammetry at different pHs. The pH dependent oxidation of metolazone occurs in two consecutive steps in a diffusion‐controlled mechanism and involves the formation of a main oxidation product. The first oxidation process is reversible, and involves two electrons and two protons corresponding to the oxidation of nitrogen in the sulfonamide moiety. The second oxidation process is irreversible, also occurs in the sulfonamide moiety, involves a one electron‐transfer, and is followed by deprotonation to produce a cation radical, which reacts with water and yields a hydroxylated product. The diffusion coefficient of metolazone was calculated to be 3.43×10^?6 cm² s^?1 in pH 7.0 0.1 M phosphate buffer.     

Poly(neutral red): Electrosynthesis,Characterization, and Application as a Redox Mediator

The synthesis by electropolymerization, the characterization, and applications of poly(neutral red) (PNR), including as a redox mediator, are reviewed. PNR's high electrical conductivity and its redox characteristics have led to special applications of the polymer, and it has been used for the development of electrochemical and optical sensors. Moreover, the attractive properties of PNR allow it to be applied in the development of electrochemical biosensors. Future perspectives are indicated.     

Novel ion traps using planar resistive electrodes: Implications for miniaturized mass analyzers

In radiofrequency ion traps, electric fields are produced by applying time-varying potentials between machined metal electrodes. The electrode shape constitutes a boundary condition and defines the field shape. This paper presents a new approach to making ion traps in which the electrodes consist of two ceramic discs, the facing surfaces of which are lithographically imprinted with sets of concentric metal rings and overlaid with a resistive material. A radial potential function can be applied to the resistive material such that the potential between the plates is quadrupolar, and ions are trapped between the plates. The electric field is independent of geometry and can be optimized electronically. The trap can produce any trapping field geometry, including both a toroidal trapping geometry and the traditional Paul-trap field. Dimensionally smaller ion trajectories, as would be produced in a miniaturized ion trap, can be achieved by increasing the potential gradient on the resistive material and operating the trap at higher frequency, rather than by making any physical changes to the trap or the electrodes. Obstacles to miniaturization of ion traps, such as fabrication tolerances, surface smoothness, electrode alignment, limited access for ionization or ion injection, and small trapping volume are addressed using this design.     

Spiroacetal biosynthesis in insects from Diptera to Hymenoptera: the Giant Ichneumon wasp Megarhyssa nortoni nortoni Cresson

The volatile components of the mandibular gland secretion generated by the Giant Ichneumon parasitoid wasp Megarhyssa nortoni nortoni Cresson are mainly spiroacetals and methyl ketones, and all have an odd number of carbon atoms. A biosynthetic scheme rationalizing the formation of these diverse components is presented. This scheme is based on the results of incorporation studies using (2)H-labeled precursors and [(18)O]dioxygen. The key steps are postulated to be decarboxylation of beta-ketoacid equivalents, beta-oxidation (chain shortening), and monooxygenase-mediated hydroxylation leading to a putative ketodiol that cyclizes to spiroacetals. The generality of the role of monooxygenases in spiroacetal formation in insects is considered, and overall, a cohesive, internally consistent theory of spiroacetal generation by insects is presented, against which future hypotheses will have to be compared.     

Synthesis of high molecular weight comb block copolymers and their assembly into ordered morphologies in the solid state

This Article describes a simple two-step synthesis of comb block copolymers with molecular weights exceeding 1,000,000 g mol(-1) and their assembly into ordered morphologies in the solid state. This work is exciting because these polymers assembled into morphologies with domain sizes exceeding 100 nm and, in some examples, 200 nm without the use of additives. These materials reflected selected wavelengths of visible light, and these wavelengths could be affected by swelling with methylene chloride vapor. A comparison between the structures of comb block copolymers and linear block copolymers is presented with a discussion of important parameters affecting their assembly in the solid state. This Article will first describe the synthesis of comb block copolymers using ring opening metathesis polymerization and atom transfer radical polymerization and their subsequent characterization. The comb block copolymers, backbone polymers, and polystyrene arms were all characterized independent of each other and had low polydispersities. The comb block copolymers were assembled by dissolving in methylene chloride and allowing the solvent to evaporate. After thermal annealing, the polymers were characterized by scanning electron and optical microscopy. These polymers assembled into spherical, lamellar, and cylindrical arrays with domain sizes from 132 to 258 nm. This work extends the molecular architectures of polymers that can be assembled in the solid state, the molecular weights of block copolymers that were assembled, and the domain sizes that can be realized without the use of additives.     

Evaluation of monolithic and sub 2 microm particle packed columns for the rapid screening for illicit drugs--application to the determination of drug contamination on Irish euro banknotes

A study comparing recently available 100 x 3 mm id, 200 x 3 mm id monolithic reversed-phase columns with a 50 x 2.1 mm id, 1.8 microm particle packed reversed-phase columns was carried out to determine the most efficient approach (using traditional van Deemter analysis and a modern kinetic plot approach) for the rapid screening of samples for 16 illicit drugs and associated metabolites. A plot of column backpressure versus plate number (N) showed a significant advantage of using the monolithic phases, with the 20 cm monolithic column exhibiting a maximum 15,000 plates at a column backpressure of approximately 70 bar, compared to approximately 7000 plates at 150 bar for the 5 cm 1.8 microm particle packed column. Optimum linear velocities were found to be 0.40 mm s(-1), 0.52 mm s(-1) and 0.98 mm s(-1) for the three above columns, respectively. The 20 cm monolithic column was subsequently applied to the separation and determination of illicit drug contamination on Irish euro banknotes, using methanol extraction followed by LC-MS/MS. Method performance data showed that the new LC-MS/MS method was significantly more sensitive than previous GC-MS/MS based methods for this application, with detection limits in the pg note(-1) region, based upon a 20 microL standard injection. All of the notes examined tested positive for trace quantities of cocaine, with benzoylecgonine detected on 12 of the 45 notes sampled. Traces of heroin were also detected on three of the 45 notes.