KINETIC STUDY OF THE REACTIONS OF TRIARYLPHOSPHINES WITH α-HALO SULFONES

Abstract

Reaction of a series of triarylphosphines with α-halo-m-cyanobenzyl phenyl sulfones gives the following Hammett ρ values: (CI) ρ = ?1.84; (Br) ρ = ?3.03; (I) ρ = ?3.36.     

Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles

Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).     

Protein and mRNA Delivery Enabled by Cholesteryl-Based Biodegradable Lipidoid Nanoparticles

Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).     

Activity Coefficients of Individual Ions from Titration Data

It is shown that the activity coefficients of the anions resulting from the dissociation of a weak polyprotic acid can be obtained from titration data. Activity coefficients are determined in terms of the activity coefficient of the undissociated acid. The extracted activity coefficients are also dependent on the pH scale adopted in the titration process and are considered as operational coefficients. The computational procedure uses an exact equation representing the titration curve and a nonlinear least-squares fitting procedure. As an illustration, the activity coefficients of the anions of succinic acid are determined. The method also allows study of the variation of the activity coefficients with the ionic strength in a straightforward manner.     

Cu(I) complexes containing a multidentate and conformationally flexible dibenzylidene acetone ligand (dbathiophos): application in catalytic alkene cyclopropanation

The synthesis and characterisation of a multidentate conformationally flexible ligand based on the dibenzylidene acetone core structure, dbathiophos (1), is described. Ligand 1 has a high affinity for cationic and neutral Cu(I) species. Three unique Cu(I) complexes (4-6) are reported showing that the ligand backbone of dbathiophos is hemilabile, and able to adopt different 1,4-dien-3-one conformational geometries around Cu(I). Complexes 4 and 6 both effectively catalyse the cyclopropanation of styrene with ethyl diazoacetate at low catalyst loadings (1 mol% Cu).     

Crystalline hydration structure at the membrane-fluid interface of model lipid rafts indicates a highly reactive boundary region

The fluid mosaic model of biological membranes is that of a two-dimensional lipid bilayer in which both lipids and associated membrane proteins diffuse freely. More recently, the raft hypothesis proposed that membranes contain small, dynamic, functional domains (rafts), which act as platforms for membrane protein attachment and interaction. Although experimental evidence supporting the raft hypothesis is growing, very little is known of the structure of the membrane-fluid interface of lipid raft systems. Here, we report the direct submolecular-scale imaging of model raft membranes using ultrahigh resolution atomic force microscopy. We characterize the heterogeneous nature of crystalline hydration layers at the membrane-fluid interface. The association of crystalline hydration layers with raft membranes would significantly affect the mechanism and kinetics of both inter-raft interactions and those between rafts and external biomolecules, and therefore this finding has important implications for membrane biology.     

Mechanism of necking as revealed by ultrasonic cavitation of polyethylene single crystals

Ultrasonic cavitation of polyethylene single crystals and single-crystal aggregates in the form of cakes results in lamella fragmentation and necking involving the transformation of lamellar crystals into fibrillar crystals between 20 to 400 Å in diameter. The smaller fibrils (～20–30 Å) have a very smooth appearance, whereas the larger ones (～100–400 Å) contain a beady structure about 100 Å periodically spaced along the fibrils. The smoother microfibrils are suggested to contain extended chains that are formed by unfolding of molecules directly from the chain-folded lamellae as well as from the folded-chain crystals contained within the beady fibrils. The presence of the chain-folded crystals within the larger beady fibrils is shown in numerous instances to be due to incorporation of mosaic crystalline blocks originally present, but weakly connected to one another, in the lamellar single crystals. The necking process is deduced by observation to involve primarily a mechanical shearing of mosaic crystalline blocks along the c-axis plus a rotation into the fibril direction. Observation of extreme resistance of lamellae in the overgrowth regions to cavitation damage suggests the presence of tie molecules and/or interpenetrating cilia between these lamellae. The suggestion finds strong support from additional studies carried out on lamellae that have been tied together at the folds by cross-linking with γ rays.     

Efficient synthesis of the siderophore petrobactin via antimony triethoxide mediated coupling

Chemical synthesis of petrobactin, a siderophore for Bacillus anthracis, has been achieved via Sb(OEt)₃-mediated ester–amide exchange.     

Enhanced resonator sensitivity with nanostructured porous silica coatings

We present a strategy to increase the sensitivity of resonators to the presence of specific molecules in the gas phase, measured by the change in resonant frequency as the partial pressure of the molecule changes. We used quartz crystals as the resonators and coated them with three different thin films (<1 microm thick) of porous silica: silica xerogel, silica templated by an ordered hexagonal phase of surfactant micelles, and silica templated by an isotropic L3 phase surfactant micellar system. We compared the sensitivity of coated resonators to the presence of water vapor. The crystals coated with hexagonal phase-templated silica displayed a sensitivity enhancement up to 100-fold compared to an uncoated quartz crystal in the low-pressure regime where adsorption played a dominant role. L3 phase-templated silica displayed the highest sensitivity (up to a 4000-fold increase) in the high partial pressure regimes where capillary condensation was the main accumulation mechanism. Three parameters differentiate the contributions of these coatings to the sensitivity of the underlying resonator: (i) specific surface area per unit mass of the coating, (ii) accessibility of the surfaces to a target molecule, and (iii) distribution in the characteristic radii of curvature of internal surfaces, as measured by capillary condensation.