Microflow photochemistry—a reactor comparison study using the photochemical synthesis of terebic acid as a model reaction

The continuous-microflow photochemical synthesis of terebic acid from maleic acid was investigated in two different microreactor set-ups. The results were subsequently compared to analogue experiments in a conventional chamber reactor. Based on conversion rates, reactor design and energy efficiency calculations, the simple microcapillary reactor showed the best overall performance.     

Enhanced transdermal delivery by using electrostatically interactive chitosan nanocapsules

This paper describes a useful means of noninvasively enhancing transdermal delivery efficiency. For this, chitosan nanocapsules with positive surface charges were fabricated by using the in situ precipitation method. These nanocapsules cannot only have an ability to encapsulate the drug molecule (this study used riboflavin 5′-monophosphate), but also electrotatically interact with the stratum corneum layer. To demonstrate this, fluorescence-labeled polymer nanoparticles with different particle sizes as well as surface charges were topically applied onto the skin and their distribution was directly imaged. This demonstration experiment allowed us to figure out that once the nanocapsules were provided with positive surface charges, they readily deposited into the stratum corneum layer due to the electrostatic interaction. Further quantitative characterization of the penetrating amount of riboflavin 5′-monophosphate by using the Frantz diffusion cell method showed that our chitosan nanocapsule system effectively improved transdermal delivery efficiency.     

No-wash protein labeling with designed fluorogenic probes and application to real-time pulse-chase analysis

Small molecule labeling techniques for cellular proteins under physiological conditions are very promising for revealing new biological functions. We developed a no-wash fluorogenic labeling system by exploiting fluorescence resonance energy transfer (FRET)-based fluorescein-cephalosporin-azopyridinium probes and a mutant β-lactamase tag. Fast quencher elimination, hydrophilicity, and high resistance against autodegradation were achieved by rational refinement of the structure. By applying the probe to real-time pulse-chase analysis, the trafficking of epidermal growth factor receptors between cell surface and intracellular region was imaged. In addition, membrane-permeable derivatization of the probe enabled no-wash fluorogenic labeling of intracellular proteins.     

Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry

This study describes the development of a rapid and sensitive high‐performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC‐MS/MS) assay for the quantification of [6]‐gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 → 177.1 for [6]‐gingerol and 294.2 → 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10–10,000 ng/mL (r ≥ 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 μL). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]‐gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]‐gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration‐time curve (AUC_inf) with no significant change in the systemic clearance (Cl_s), volume of distribution (V_ss) and elimination half‐life (t_1/2) as a function of dose. Copyright © 2011 John Wiley & Sons, Ltd.     

Self-deprotonation and colorization of 1,3-bis(dicyanomethylidene)indan in polar media: a facile route to a minimal polymethine dye for NIR fluorescence imaging

Colorless 1,3-bis(dicyanomethylidene)indan is an organic acid (pK(a) ≈3.0) that turns blue in polar media owing to self-deprotonation. Moreover, its colored conjugate base shows potential as a minimal anionic polymethine dye for probing biomolecules in cells and in vivo through noncovalent complexation and near-infrared fluorescence signaling.     

A lectin-coupled,multiple reaction monitoring based quantitative analysis of human plasma glycoproteins by mass spectrometry

Aberrant protein glycosylation may be closely associated with cancer pathology. To measure the abundance of protein glycoforms with a specific glycan structure in plasma samples, we developed a lectin-coupled multiple reaction monitoring (MRM)-based mass spectrometric method. It was confirmed that the method could provide reproducible results with precision sufficient to distinguish differences in the abundance of protein glycoforms between individuals. Plasma samples prepared from hepatocellular carcinoma (HCC) patients without immuno-depletion of highly abundant plasma proteins were fractionated by use of fucose-specific aleuria aurantia lectin (AAL) immobilized on magnetic beads by use of a biotin–streptavidin conjugate. The lectin-captured fractions were digested by trypsin and profiled by tandem mass spectrometry. From the proteomic profiling data, target glycoproteins were selected and analyzed quantitatively by MRM-based analysis. The reproducibility of MRM-based quantification of the selected target proteins was reliable, with precision (CV; ≤14% for batch-to-batch replicates and ≤19% for replicates over three days) sufficient to distinguish differences in the abundance of AAL-captured glycoforms between individual plasma samples. This lectin-coupled, MRM-based method, measuring only lectin-captured glycoforms of a target protein rather than total target protein, is a tool for monitoring differences between individuals by measuring the abundance of aberrant glycoforms of a target protein related to a disease. This method may be further applied to rapid verification of biomarker candidates involved in aberrant protein glycosylation in human plasma.     

Copper-mediated sequential cyanation of aryl C-B and arene C-H bonds using ammonium iodide and DMF

The cyanation of aromatic boronic acids, boronate esters, and borate salts was developed under copper-mediated oxidative conditions using ammonium iodide and DMF as the source of nitrogen and carbon atom of the cyano unit, respectively. The procedure was successfully extended to the cyanation of electron-rich benzenes, and regioselective introduction of a cyano group at the arene C-H bonds was also achieved. The observation that the reaction proceeds via a two-step process, initial iodination and then cyanation, led us to propose that ammonium iodide plays a dual role to provide iodide and nitrogen atom of the cyano moiety.     

Surface-dependent, ligand-mediated photochemical etching of CdSe nanoplatelets

Photochemical etching of CdSe nanoplatelets was studied to establish a relationship between the nanocrystal surface and the photochemical activity of an exciton. Nanoplatelets were synthesized in a mixture of octylamine and oleylamine for the wurtzite (W) lattice or in octadecene containing oleic acid for the zinc-blende (ZB) lattice. For photochemical etching, nanoplatelets were dispersed in chloroform containing oleylamine and tributylphosphine in the absence or presence of oleic acid and then irradiated with light at the band-edge absorption maxima. Etching phenomena were characterized using UV-vis absorption spectroscopy and transmission electron microscopy. The absorption spectra of both W and ZB CdSe nanoplatelets showed that the exciton was confined in one dimension along the thickness. However, the two nanoplatelets presented different etching kinetics and erosion patterns. The rate of etching for W CdSe nanoplatelets was much faster than that for ZB nanoplatelets. Small holes were uniformly perforated on the planar surface of W nanoplatelets, whereas the corners and edges of ZB nanoplatelets were massively eroded without a significant perforation on the planar surface. This suggests that the amine-passivated surface of trivalent cadmium atoms on CdSe nanoplatelets is photochemically active, but the carboxylate-passivated surface of divalent cadmium atoms is not. Hence, the ligand, which induces the growth of W or ZB CdSe nanoplatelets, mediates the surface-dependent photochemical etching. This result implies that an electron-hole pair can be extracted from the planar surface of amine-passivated W nanoplatelets but from the corners and edges of carboxylate-passivated ZB nanoplatelets.