An Aerobic Alternative to Oxidative Ozonolysis of Styrenes

A general, selective and extremely efficient procedure for the aerobic cleavage of aromatic alkenes is presented. TON values in the range 6,000,000–10,000,000 are obtained for this nickel‐catalyzed reaction performed in polyethylene glycol 400 under 1 atm of molecular oxygen. Mono‐, di‐, tri‐ and tetrasubstituted styrene derivatives are oxidatively cleaved by this reproducible protocol, also suitable for larger scale (1.5 g) reactions. The presence of several functional groups (alkyl, alkoxy, halogen, trifluoromethyl) is tolerated in the substrates. The mechanistic proposal to explain the selective generation of carboxylic acids and ketones from aromatic alkenes involves the participation of the polyol solvent in the presented oxidative process.

     

Influence of Surfactant on the Characteristics of W1/O/W2-Microparticles

The water-in-oil-in water (W₁/O/W₂) double emulsion evaporation technique is widely used when the microencapsulation of soluble agents like naloxone HCl is intended. The present work shows the effect of HLB emulsifiers added to phase O on microsphere morphology, size, release, drug encapsulation efficiency. The addition of sorbitan ester to first emulsion (W₁/O) and the HLB of the surfactant have an important effect on the characteristics of poly-lactide-co-glycolide (PLGA) microparticles (MP). This MP with sorbitan esters added were smaller and released the hydrophilic drug, naloxone, with no-significant difference at pH 5 versus pH 7.5 (phosphate medium). This is an important fact when long-drug release is considered since it is known that PLGA degradation leads to media acidification. The HLB value had an important effect on drug loading. Sorbitan monooleate led to the highest naloxone loading. Because of its low HLB (4.3), it is most suitable for stabilizing the W₁/O emulsion, which is fundamental for the successful entrapment of a hydrophilic compound in MP prepared by double emulsion technique. Finally, drug solubility in the MP matrixes cannot be considered as a predictive parameter for drug encapsulation. Both surfactants increased the naloxone solubility in the polymer PLGA and only sorbitan monooleate increased the drug entrapment.     

Repurposing the Chemical Scaffold of the Anti‐Arthritic Drug Lobenzarit to Target Tryptophan Biosynthesis in Mycobacterium tuberculosis

The emergence of extensively drug‐resistant strains of Mycobacterium tuberculosis (Mtb) highlights the need for new therapeutics to treat tuberculosis. We are attempting to fast‐track a targeted approach to drug design by generating analogues of a validated hit from molecular library screening that shares its chemical scaffold with a current therapeutic, the anti‐arthritic drug Lobenzarit (LBZ). Our target, anthranilate phosphoribosyltransferase (AnPRT), is an enzyme from the tryptophan biosynthetic pathway in Mtb. A bifurcated hydrogen bond was found to be a key feature of the LBZ‐like chemical scaffold and critical for enzyme inhibition. We have determined crystal structures of compounds in complex with the enzyme that indicate that the bifurcated hydrogen bond assists in orientating compounds in the correct conformation to interact with key residues in the substrate‐binding tunnel of Mtb‐AnPRT. Characterising the inhibitory potency of the hit and its analogues in different ways proved useful, due to the multiple substrates and substrate binding sites of this enzyme. Binding in a site other than the catalytic site was found to be associated with partial inhibition. An analogue, 2‐(2‐5‐methylcarboxyphenylamino)‐3‐methylbenzoic acid, that bound at the catalytic site and caused complete, rather than partial, inhibition of enzyme activity was found. Therefore, we designed and synthesised an extended version of the scaffold on the basis of this observation. The resultant compound, 2,6‐bis‐(2‐carboxyphenylamino)benzoate, is a 40‐fold more potent inhibitor of the enzyme than the original hit and provides direction for further structure‐based drug design.     

Supercritical fluid extraction of lipids from broccoli leaves

The supercritical fluid extraction (SFE) and fractionation of lipids from broccoli leaves is presented in this work. For this purpose the effect of the different variables on the extraction was studied, obtaining the best results at 60°C, 300 bar and 3 mL/min. Two different fractions were obtained: First, the samples were extracted with pure CO₂, and afterward the residual material was extracted using CO₂ modified with 15% of methanol. The total fatty acid content of the extracts was determined by GC‐MS and compared with those results obtained by Soxhlet extraction with hexane and a chloroform/methanol (2:1) mixture. The SFE extracts presented a higher percentage of unsaturated fatty acids, especially the polyunsaturated 18:3 n ? 3. The methodology was successfully applied to the analysis of the fatty acid composition of the leaves from five different cultivars of broccoli. In all the samples the main fatty acids were α‐linolenic (18:3 n ? 3), linoleic (18:2 n ? 6), and palmitic (16:0). Among the different cultivars analyzed, Naxos variety presented the highest levels in fatty acids, while Parthenon and Viola the lowest. Practical applications: The proposed method allows the fractionation of lipids from broccoli leaves using a small volume of organic solvent and mild conditions. This is advantageous compared to conventional methods where large volumes or organic solvents are used, and the cost and time for the removal of these solvents, along with the possibility of degradation and toxicity, are the major disadvantages. The results obtained contribute to a better compositional characterization and a possible revaluation of this by‐product as a source of biologically active compounds.     

Thermal Stability of FGM Sandwich Plates Under Various Through-the-Thickness Temperature Distributions

A thermal stability analysis of functionally graded material (FGM) isotropic and sandwich plates is carried out by virtue of a refined quasi-3D Equivalent Single Layer (ESL) and Zig-Zag (ZZ) plate models developed within the framework of the Carrera Unified Formulation (CUF) and implemented within the Hierarchical Trigonometric Ritz Formulation (HTRF). The Principle of Virtual Displacements (PVD) is used both to derive the thermal stability differential equations with natural boundary conditions and to develop the HTRF. Uniform, linear, and non-linear temperature rises through-the-thickness direction are taken into account. The non-linear temperature distribution is given in different forms: 1) functionally graded; 2) solution of the one-dimensional Fourier heat conduction equation; and 3) sinusoidal. Several FGM sandwich plate configurations are investigated. Parametric studies are carried out in order to evaluate the effects of significant parameters, such as volume fraction index, length-to-thickness ratio, boundary conditions, aspect ratio, sandwich plate type, and temperature distribution through-the-thickness direction, on the critical buckling temperatures.     

Fibred semantics for feature-based grammar logic

This paper gives a simple method for providing categorial brands of feature-based unification grammars with a model-theoretic semantics. The key idea is to apply the paradigm of fibred semantics (or layered logics, see Gabbay (1990)) in order to combine the two components of a feature-based grammar logic. We demonstrate the method for the augmentation of Lambek categorial grammar with Kasper/Rounds-style feature logic. These are combined by replacing (or annotating) atomic formulas of the first logic, i.e. the basic syntactic types, by formulas of the second. Modelling such a combined logic is less trivial than one might expect. The direct application of the fibred semantics method where a combined atomic formula like np (num: sg & pers: 3rd) denotes those strings which have the indicated property and the categorial operators denote the usual left- and right-residuals of these string sets, does not match the intuitive, unification-based proof theory. Unification implements a global bookkeeping with respect to a proof whereas the direct fibring method restricts its view to the atoms of the grammar logic. The solution is to interpret the (embedded) feature terms as global feature constraints while maintaining the same kind of fibred structures. For this adjusted semantics, the anticipated proof system is sound and complete.     

Porphyrin assembly formation on helical biopolymers

Studies on the interactions oftrans-bis(N-methylpyridinium-4-yl)diphenylporphine with DNA and polyglutamate lead to a model for binding in which the porphyrin, under appropriate conditions of concentration and ionic strength, forms long-range assemblies on the polymer template. Large, conservative induced circular dichroism signals are observed in the Soret region as a result of the assembly process. The phasing of the signal is a consequence of the helical sense of the porphyrin stacking, which, in turn, reflects the helicity of the polymer. The assembly organization can be inhibited by modifying solution conditions either to make porphyrin aggregation less favorable or to convert the polymer to a nonhelical conformation.