Glyceride‐Mimetic Prodrugs Incorporating Self‐Immolative Spacers Promote Lymphatic Transport,Avoid First‐Pass Metabolism,and Enhance Oral Bioavailability

First‐pass hepatic metabolism can significantly limit oral drug bioavailability. Drug transport from the intestine through the lymphatic system, rather than the portal vein, circumvents first‐pass metabolism. However, the majority of drugs do not have the requisite physicochemical properties to facilitate lymphatic access. Herein, we describe a prodrug strategy that promotes selective transport through the intestinal lymph vessels and subsequent release of drug in the systemic circulation, thereby enhancing oral bioavailability. Using testosterone (TST) as a model high first‐pass drug, glyceride‐mimetic prodrugs incorporating self‐immolative (SI) spacers, resulted in remarkable increases (up to 90‐fold) in TST plasma exposure when compared to the current commercial product testosterone undecanoate (TU). This approach opens new opportunities for the effective development of drugs where oral delivery is limited by first‐pass metabolism and provides a new avenue to enhance drug targeting to intestinal lymphoid tissue.     

The use of acoustic radiation forces to position particles within fluid droplets

Handling of micrometer sizes particles, such as biological cells or coated beads, plays a relevant role in the field of life science. A number of devices have been presented in the last years, in which acoustic forces generated by coupling the vibration of a solid structure excited by a piezoelectric transducer to the particle suspension are used to collect particles in lines or position them in clumps on a grid. Following the trend of lab-on-a-chip devices, efforts have been made to shrink the size of such systems, aiming at less reagent consumption and shorter reaction times. The majority of these systems consist of closed fluid filled volumes, typically channels. Here the use of an open fluid volume, a droplet, is examined. By exciting resonances into the droplet positioned on a surface, particles can be gathered into a line, two parallel lines or, as the frequency of excitation is increased, into more complex patterns. Such a concentration process will have useful applications in improved detection sensitivity of low concentration particulate solutions.     

Structure and morphology of the 60/40 poly(p-oxybenzoate-co-ethylene terephthalate) copolymer

The copolyester composed of 60 mol% p-hydroxybenzoic acid and 40 mol% ethylene terephthalate has been studied extensively by earlier workers. However, some confusion exists particularly with respect to the nature of the thermal transitions and the possible presence of additional phases. In the present study we have examined this copolyester and found that it is possible to separate the material into soluble and insoluble fractions with significantly different ratios of p-hydroxybenzoic acid to ethylene terephthalate. In fact, the soluble PET-rich fraction is blocky in nature, while the PHBA-rich fraction is more random. The multiple thermal transitions can now be readily interpreted in terms of a heterogeneous composition which tends to segregate and phase separate.     

Glucose oxidase–magnetite nanoparticle bioconjugate for glucose sensing

Immobilization of bioactive molecules on the surface of magnetic nanoparticles is of great interest, because the magnetic properties of these bioconjugates promise to greatly improve the delivery and recovery of biomolecules in biomedical applications. Here we present the preparation and functionalization of magnetite (Fe₃O₄) nanoparticles 20 nm in diameter and the successful covalent conjugation of the enzyme glucose oxidase to the amino-modified nanoparticle surface. Functionalization of the magnetic nanoparticle surface with amino groups greatly increased the amount and activity of the immobilized enzyme compared with immobilization procedures involving physical adsorption. The enzymatic activity of the glucose oxidase-coated magnetic nanoparticles was investigated by monitoring oxygen consumption during the enzymatic oxidation of glucose using a ruthenium phenanthroline fluorescent complex for oxygen sensing. The glucose oxidase-coated magnetite nanoparticles could function as nanometric glucose sensors in glucose solutions of concentrations up to 20 mmol L^–1. Immobilization of glucose oxidase on the nanoparticles also increased the stability of the enzyme. When stored at 4°C the nanoparticle suspensions maintained their bioactivity for up to 3 months.     

Polymerization of Ion-Pair Comonomers of Related Structures

Two ion-pair comonomers of 2-methacryloyloxyethyltrimethyl-ammonium 2-methacryloyloxyethanesulfonate (METMAMES) and 3-acrylamido-3-methylbutyltrimethylammonium 2-acrylamido-2-methylpropanesulfonate have been synthesized. The spontaneous and radical homocopolymerizations of these monomer pairs, wherein no nonpolymerizable counterions are present, have also been studied. Moreover, the intrinsic viscosity of the homocopolymer derived from METMA MES was found to increase with increasing KCl concentration in aqueous solutions.     

Amplification of the Cotton Effect of a Single Chromophore through Liposomal Ordering—Stereochemical Assignment of Plakinic Acids I and J

A dramatic effect is observed when acyclic N‐(2‐naphthamides) of medium‐chain 1‐amino‐2‐methylalkanes are partially ordered with the help of liposomes: the Cotton effect arising from π–π* transitions of the terminal naphthamide chromophor is enormously enhanced. This effect was exploited to assign the configuration of new polyketide peroxides such as 1 from the sponge Plakortis halichondroides.

     

Ligand- and base-free copper(II)-catalyzed C-N bond formation: cross-coupling reactions of organoboron compounds with aliphatic amines and anilines

[reaction: see text] A ligandless and base-free Cu-catalyzed protocol for the cross-coupling of arylboronic acids and potassium aryltrifluoroborate salts with primary and secondary aliphatic amines and anilines is described. The process utilizes catalytic copper(II) acetate monohydrate and 4 A molecular sieves in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen. A broad range of functional groups are tolerated on both of the cross-coupling partners.     

An area model for on-chip memories and its application

An area model suitable for comparing data buffers of different organizations (e.g. caches versus register files) and arbitrary sizes is described. The area model considers the supplied bandwidth of a memory cell and includes such buffer overhead as control logic, driver logic and tag storage. The model gave less than 10% error when verified against real caches and register files. It is shown that, comparing caches and register files in terms of area for the same storage capacity, caches generally occupy more area per bit than register files for small caches because the overhead dominates the cache area at these sizes. For larger caches, the smaller storage cells in the cache provide a smaller total cache area per bit than the register set. Studying cache performance (traffic ratio) as a function of area, it is shown that, for small caches (less than the area occupied by 256 registers bits-r.b.e.-or 32 b), direct-mapped caches perform significantly better than four-way set-associative caches and, for caches of medium areas (between 256 r.b.e. and 4096 r.b.e.), both direct-mapped and set-associative caches perform better than fully associative caches     

A Photophysical Study of Sensitization‐Initiated Electron Transfer: Insights into the Mechanism of Photoredox Activity

The development of photocatalytic reactions has provided many novel opportunities to expand the scope of synthetic organic chemistry. In parallel with progress towards uncovering new reactivity, there is consensus that efforts focused on providing detailed mechanistic insight in order to uncover underlying excited‐state reactions are essential to maximise formation of desired products. With this in mind, we have investigated the recently reported sensitization‐initiated electron transfer (SenI‐ET) reaction for the C?H arylation of activated aryl halides. Using a variety of techniques, and in particular nanosecond transient absorption spectroscopy, we are able to distinguish several characteristic signals from the excited‐state species involved in the reaction, and subsequent kinetic analysis under various conditions has facilitated a detailed insight into the likely reaction mechanism.     

Effects of Plant Elicitors on Growth and Gypenosides Biosynthesis in Cell Culture of Giao co lam (Gynostemma pentaphyllum)

Giao co lam (Gynostemma pentaphyllum (Thunb.) Makino) is used in Northeast and Southeast Asia countries for the treatment of various diseases, including hepatitis, diabetes, and cardiovascular disease. G. pentaphyllum saponins (gypenosides) are the major components responsible for the pharmacological activities. In this study, different concentrations of abiotic (25–200 μM methyl jasmonate-MeJA and salicylic acid-SA) or biotic elicitors (1–5 g/L yeast extract-YE and Fusarium biomass) were used as plant elicitors, in order to investigate their influences on cell growth and gypenosides accumulation in G. pentaphyllum suspension cells. Suspension cells were grown on a MS medium containing 2.0 mg/L KIN and 0.5 mg/L IBA, with initial inoculum sizes of 3 g and shaking speeds of 120 rpm for 18 days. Gypenoside and Rb1 contents were measured by colorimetric and HPLC methods. Among three elicitors, SA was suitable for gypenosides accumulation in individual treatment. The cell biomass had the same values in elicitated and control suspension cells. Gypenosides content in cells treated with 100 μM salicylic acid after 6 days of culture reached a maximum value of 79.721 mg gypenoside/g dry biomass (including 0.093 mg ginsenoside Rb1/mg dry weight), which was 2.18-folds higher than that of the natural product. The elicitation promises an efficiency strategy for the production gypenosides in Gynostemma pentaphyllum suspension cells.