Dramatic increase of quench efficiency in "spacerless" dimaleimide fluorogens

In this post-genomic era, new techniques are needed to cope with the task of assigning functional roles to the huge number of identified putative gene products. We have developed a minimalist labelling strategy based on the use of synthetic fluorogenic probe reagents that fluoresce only after their reaction with a target peptide sequence. The probe reagents have fluorescent cores and bear two maleimide groups, such that their latent fluorescence is quenched by a photoinduced electron transfer (PET) to the pendant maleimide groups, until both of these groups undergo a specific thiol addition reaction. The efficiency of the fluorescence quenching is critical to the practicality of this labelling method, and has been predicted to be related to the intramolecular distance between the fluorophore and the maleimide groups. We have conducted the first direct test of this hypothesis by preparing a series of novel fluorogens that differ only by the spacer moiety separating their coumarin fluorophore and their dimaleimide fragment. A striking correlation was observed between intramolecular distance and the fluorescence enhancement (FE) observed after reaction with two equivalents of thiol. Guided by this observation, we then designed 'spacerless' fluorogens, of which a dansyl derivative shows an FE ratio of >300, the largest recorded for dimaleimide fluorogens. The trends observed herein provide valuable lessons for subsequent fluorogen design, and the novel fluorogens developed in the course of this study are currently being applied to protein labelling applications.     

The first C-glycosidic analogue of a novel galactosyltransferase inhibitor

Structural analogues and mimics of the natural sugar-nucleotide UDP-galactose (UDP-Gal) are sought after as chemical tools for glycobiology and drug discovery. We have recently developed a novel class of galactosyltransferase (GalT) inhibitors derived from UDP-Gal, bearing an additional substituent at the 5-position of the uracil base. Herein we report the first C-glycosidic derivative of this new class of GalT inhibitors. We describe a practical convergent synthesis of the new UDP-C-Gal derivative, including a systematic study into the use of radical chemistry for the preparation of galactosyl ethylphosphonate, a key synthetic intermediate. The new inhibitor showed activity against a bacterial UDP-Gal 4'-epimerase at micromolar concentrations. This is the first example of a base-modified UDP-sugar as an inhibitor of a UDP-sugar-dependent enzyme which is not a glycosyltransferase, and these results may therefore have implications for the design of inhibitors of these enzymes in the future.     

In situ synthesis of stable mixed ligand Fe2+ complexes on bipyridinyl functionalized electrodes and nanotube supports

A simple method is presented to synthesize asymmetric mixed ligand iron(II) diimine complexes using bipyridinyl functionalized carbon nanotubes. The synthesis of these complexes was realized using subsequent dip coating processes. The in situ formed mixed ligand complexes were used in aqueous media to act as building blocks in biosensor devices.     

An Overview of Molecular Spectroscopic Studies on Theobromine and Related Alkaloids

Abstract: An overview of the recent molecular spectroscopic work on the methylxanthine alkaloid theobromine and its two closely related relatives, caffeine and theophylline, is presented. The role of molecular spectroscopy in studies of the coordination chemistry of these methylxanthine compounds is also briefly discussed.     

Fabrication and characterization of nanorod solar cells with an ultrathin a-Si:H absorber layer

In this paper, we present a three-dimensional nanorod solar cell design. As the backbone of the nanorod device, density-controlled zinc oxide (ZnO) nanorods were synthesized by a simple aqueous solution growth technique at 80 °C on ZnO thin film pre-coated glass substrate. The as-prepared ZnO nanorods were coated by an amorphous hydrogenated silicon (a-Si:H) light absorber layer to form a nanorod solar cell. The light management, current–voltage characteristics and corresponding external quantum efficiency of the solar cells were investigated. An energy conversion efficiency of 3.9% was achieved for the nanorod solar cells with an a-Si:H absorber layer thickness of 75 nm, which is significantly higher than the 2.6% and the 3.0% obtained for cells with the same a-Si:H absorber layer thickness on planar ZnO and on textured SnO₂:F counterparts, respectively. A short-circuit current density of 11.6 mA/cm² and correspondingly, a broad external quantum efficiency profile were achieved for the nanorod device. An absorbed light fraction higher than 80% in the wavelength range of 375–675 nm was also demonstrated for the nanorod solar cells, including a peak value of ~ 90% at 520–530 nm.     

Modeling of (vapor + liquid) equilibrium and enthalpy of solution of carbon dioxide (CO2) in aqueous methyldiethanolamine (MDEA) solutions

A thermodynamic model was used to estimate enthalpy of solution of carbon dioxide (CO₂) in methyldiethanolamine (MDEA) aqueous solutions. The model was based on a set of equations for chemical equilibria, phase equilibria, charge, and mass balances. Non-ideality in the liquid phase was taken into account by interaction parameters fitted to (vapor + liquid) equilibrium data.The enthalpies of solution of CO₂ were derived from the model using classical thermodynamic relations and were compared to experimental values obtained in previous works.     

Fast LC–MS Electrospray Ionization for the Quantification of Digoxin in Human Plasma and Its Application to Bioequivalence Studies

A fast, sensitive and specific liquid chromatography-mass spectrometry method has been developed for quantification of digoxin in human plasma. The method was optimized to bioequivalence studies aiming higher sensitivity and selectivity than previously published methods, in addition to shorter run time allowing high-throughput sample analyses from volunteers. Chromatographic separation was achieved by an RP-18e column hyphenated to an API 5000 mass spectrometer system set at negative electrospray ionization and operating in the MRM mode. Calibration curve was linear over a wide range of concentration (50.0–6000.0 pg mL⁻¹), with the lower limit of quantification at 50.0 pg mL⁻¹ and without interfering peaks at the retention time of digoxin (2.09 min). Dexamethasone was used as internal standard and samples were cleaned up by liquid-liquid extraction obtaining a mean recovery of 73.8%. Validation results confirmed inter-batch accuracy (−8.66 to 5.78%), precision (4.1–10.6%) and stability, in accordance with the U.S. Food and Drug Administration and the Brazilian National Health Surveillance Agency guidelines. The developed analytical method could be successfully applied to a single oral dose (0.25 mg), one-way, randomized, two-sequence, crossover bioequivalence study validating, up to date, the fastest analysis and the most sensitive and specific method already published for digoxin quantification.

     

Controllability Issues for Continuous-Spectrum Systems and Ensemble Controllability of Bloch Equations

We study the controllability of the Bloch equation, for an ensemble of non interacting half-spins, in a static magnetic field, with dispersion in the Larmor frequency. This system may be seen as a prototype for infinite dimensional bilinear systems with continuous spectrum, whose controllability is not well understood. We provide several mathematical answers, with discrimination between approximate and exact controllability, and between finite time or infinite time controllability: this system is not exactly controllable in finite time T with bounded controls in L ²(0, T), but it is approximately controllable in L ^∞ in finite time with unbounded controls in L^￥_loc([0,+￥)){L^{\infty}_{loc}([0,+\infty))}. Moreover, we propose explicit controls realizing the asymptotic exact controllability to a uniform state of spin + 1/2 or −1/2.     

Strain‐Promoted 1,3‐Dithiolium‐4‐olates–Alkyne Cycloaddition

Reported here is the reactivity of mesoionic 1,3‐dithiolium‐4‐olates towards strained alkynes, leading to thiophene cycloaddition products. In the process, the potential of these dipoles towards orthogonal reaction with azides, allowing efficient double ligation reactions, was discovered. A versatile process to access benzo[c]thiophenes, in an unprecedented divergent fashion, was developed and provides a new entry to unconventional polyaromatic thiophenes.