A Designed 5‐Fluorouracil‐Based Bridged Silsesquioxane as an Autonomous Acid‐Triggered Drug‐Delivery System

Two new prodrugs, bearing two and three 5‐fluorouracil (5‐FU) units, respectively, have been synthesized and were shown to efficiently treat human breast cancer cells. In addition to 5‐FU, they were intended to form complexes through H‐bonds to an organo‐bridged silane prior to hydrolysis‐condensation through sol–gel processes to construct acid‐responsive bridged silsesquioxanes (BS). Whereas 5‐FU itself and the prodrug bearing two 5‐FU units completely leached out from the corresponding materials, the prodrug bearing three 5‐FU units was successfully maintained in the resulting BS. Solid‐state NMR (²⁹Si and ¹³C) spectroscopy show that the organic fragments of the organo‐bridged silane are retained in the hybrid through covalent bonding and the ¹H NMR spectroscopic analysis provides evidence for the hydrogen‐bonding interactions between the prodrug bearing three 5‐FU units and the triazine‐based hybrid matrix. The complex in the BS is not affected under neutral medium and operates under acidic conditions even under pH as high as 5 to deliver the drug as demonstrated by HPLC analysis and confirmed by FTIR and ¹³C NMR spectroscopic studies. Such functional BS are promising materials as carriers to avoid the side effects of the anticancer drug 5‐FU thanks to a controlled and targeted drug delivery.     

Polyluminol/hydrogel composites as new electrochemiluminescent-active sensing layers

This paper reports on electrochemiluminescent sensors and biosensors based on polyluminol/hydrogel composite sensing layers using chemical or biological membranes as hydrogel matrices. In this work, luminol is electropolymerized under near-neutral conditions onto screen-printed electrode (SPE)-supported hydrogel films. The working electrode coated with a hydrogel film is soaked in a solution containing monomeric luminol units, allowing the monomeric luminol units to diffuse inside the porous matrix to the electrode surface where they are electropolymerized by cyclic voltammetry (CV). Sensors and enzymatic biosensors for H₂O₂ and choline detection, respectively, have been developed, using choline oxidase (ChOD) as a model enzyme. In this case, hydrogel is used both as the enzymatic immobilization matrix and as a template for the electrosynthesis of polyluminol. The enzyme was immobilized by entrapment in the gel matrix during its formation before electropolymerization of the monomer. Several parameters have been optimized in terms of polymerization conditions, enzyme loading, and average pore size. Using calcium alginate or tetramethoxysilane (TMOS)-based silica as porous matrix, H₂O₂ and choline detection are reported down to micromolar concentrations with three orders of magnitude wide dynamic ranges starting from 4?×?10^?7 M. Polyluminol/hydrogel composites appear as suitable electrochemiluminescence (ECL)-active sensing layers for the design of new reagentless and disposable easy-to-use optical sensors and biosensors, using conventional TMOS-based silica gel or the more original and easier to handle calcium alginate, reported here for the first time in such a configuration, as the biocompatible hydrogel matrix. Figure

Elaboration of electrochemiluminent polyluminol/hydrogel composite sensing layers     

Cosine modulated HSQC: a rapid determination of (3)J(HNHalpha) scalar couplings in (15)N-labeled proteins

A two-dimensional HSQC-based NMR method, (15)N-COSMO-HSQC, is presented for the rapid determination of homonuclear (3)J(HNHalpha) couplings in (15)N-labeled proteins in solution. Scalar couplings are extracted by comparing the intensity of two separate datasets recorded with and without decoupling of the (3)J(HNHalpha) during a preparation period. The scalar couplings are introduced through a cosine modulation of the peak intensities. The experiment relies on a BIRD sandwich to selectively invert all amide protons H(N) and is very simple to implement. (3)J(HNHalpha) couplings were determined using both the (15)N-COSMO-HSQC and quantitative-J on (15)N-labeled chemokine RANTES. The two experiments show well-correlated values.     

Synthesis of novel KDR kinase inhibitors through catalytic reductive cyclization of o-nitrobenzylcarbonyl compounds

An efficient synthesis of o-nitrobenzylcarbonyl compounds is demonstrated through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.     

Theoretical contact angles on a nano-heterogeneous surface composed of parallel apolar and polar strips

Neumann-Good's parallel strip model (J. Colloid Interface Sci. 1972, 38, 341) was used to analyze the contact angle hysteresis for a liquid on a heterogeneous surface composed of alternatively aligned horizontal apolar (theta = 70 degrees ) and polar (theta = 0 degree ) strips. The critical size of the strip width, below which the contact angle hysteresis disappears, was determined on the basis of the analysis of the activation energy for wetting to be from 6 to 12 nm. This calculated value of the critical strip size is 1 order of magnitude smaller than that of 0.1 microm, which has been commonly considered as the limit of heterogeneity size causing the appearance of the contact angle hysteresis.     

Efficient synthesis of a nucleoside-diphospho-exo-glycal displaying time-dependent inactivation of UDP-galactopyranose mutase

A short and efficient synthesis of UDP-exo-galactofuranosyl-glycal is presented. This molecule displayed an interesting time-dependent inactivation of UDP-galactopyranose mutase, an essential enzyme of the mycobacterial cell wall biosynthesis.     

Development of form and function in peripheral auditory structures of the zebrafish (Danio rerio)

Investigations of the development of auditory form and function have, with a few exceptions, thus far been largely restricted to birds and mammals, making it difficult to postulate evolutionary hypotheses. Teleost fishes represent useful models for developmental investigations of the auditory system due to their often extensive period of posthatching development and the diversity of auditory specializations in this group. Using the auditory brainstem response and morphological techniques we investigated the development of auditory form and function in zebrafish (Danio rerio) ranging in size from 10 to 45 mm total length. We found no difference in auditory sensitivity, response latency, or response amplitude with development, but we did find an expansion of maximum detectable frequency from 200 Hz at 10 mm to 4000 Hz at 45 mm TL. The expansion of frequency range coincided with the development of Weberian ossicles in zebrafish, suggesting that changes in hearing ability in this species are driven more by development of auxiliary specializations than by the ear itself. We propose a model for the development of zebrafish hearing wherein the Weberian ossicles gradually increase the range of frequencies available to the inner ear, much as middle ear development increases frequency range in mammals.