Understanding the role of carbamate reactivity in fatty acid amide hydrolase inhibition by QM/MM mechanistic modelling

QM/MM modelling of FAAH inactivation by O-biphenyl-3-yl carbamates identifies the deprotonation of Ser241 as the key reaction step, explaining why FAAH is insensitive to the electron-donor effect of conjugated substituents; this may aid design of new inhibitors with improved selectivity and in vivo potency.     

Efficient and convenient synthesis,characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines

In the present study, 20 new tetracyclic 1,4-benzothiazines (4a–4 t) were conveniently synthesized in good yields and characterized by different spectral and physical techniques. The in vitro antimicrobial evaluation of the synthesized benzothiazine derivatives was performed by serial dilution against two Gram-positive bacteria [Bacillus subtilis (MTCC 441) and Staphylococcus epidermidis (MTCC 6880)], two Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)], and two fungal strains [Candida albicans (MTCC 227) and Aspergillus niger (MTCC 8189)]. The derivatives 4 l and 4 t were found to be more potent than standard drug, i.e., fluconazole, against A. niger and C. albicans, respectively.     

Sonochemical preparation of GaSb nanoparticles

A room temperature sonochemical method for the preparation of GaSb nanoparticles using less hazardous Ga and antimony chloride (SbCl(3)) as the precursors has been described. The formation of GaSb has been confirmed by means of XRD, EDAX, and XPS characterization. TEM and SAED results show that the as-prepared solid consists of nanosized GaSb crystals with sizes in the range 20-30 nm. The photoacoustic spectrum result reveals that the GaSb nanoparticles have a direct band gap of about 1.21 eV. On the basis of the control experiments and the extreme conditions produced by ultrasound, an ultrasound-assisted in-situ reduction/combination mechanism has been proposed to explain the reaction.     

Liquid crystalline ionomers. II. Main chain liquid crystalline polymers with terminal sulfonate groups

Liquid crystalline ionomers containing sulfonate groups on the terminal unit of the chain were synthesized by an interfacial condensation reaction of 4,4′-dihydroxy-α,α′-dimethyl benzalazine, the monofunctional dye fast yellow (FY), and a 50/50 mixture of sebacoyl and dodecanedioyl dichlorides. The weight-average molecular weights were estimated from inherent viscosity measurements to be between 6000–11,000 and the sodium sulfonate concentrations ranged from 0–18.4 meq/100 g polymer. Elemental analyses, however, indicated much higher molecular weights, which suggested that there was a distribution of chains with one, two, or no FY endgroups. The polymers were semicrystalline and melted at ca. 140°C to form nematic mesophases that were stable over a temperature range of ca. 80°C. They were thermally stable to about 350°C. The ionomeric nature of the polymers was confirmed by the presence of intermolecular associations in nonpolar solvents, as demonstrated by dilute solution viscosity measurements.     

Regiochemical variation in the electrophilic addition of HBr to 1-phenylprop-1-yne

The reaction of aryl alkynes with dilute methylene chloride solutions of quaternary ammonium bromide and 20% trifluoroacetic acid produces primarily the syn Markovnikov adducts of hydrogen bromide. At moderate concentrations of the bromide, the principal product is the Markovnikov anti adduct. At high concentrations of bromide, the anti-Markovnikov anti addition product predominates.     

Transgenic Expression and Functional Characterization of Human Platelet Derived Growth Factor BB (hPDGF-BB) in Tobacco (Nicotiana tabacum L.)

Recombinant human platelet derived growth factor BB (rhPDGF-BB) is clinically approved for treating diabetic neuropathic ulcers. Plant-based expression systems offer less expensive ways of producing recombinant drugs, which do not require purification for clinical use. From this perspective, rhPDGF-BB is an ideal candidate for expression in plants as it can be applied topically. Here, we report a proof of concept study, in which rhPDGF-BB was expressed in tobacco plants, and its biological activity was tested in vitro. The mature human platelet derived growth factor BB (hPDGF-BB) gene was codon-optimized for tobacco and fused with ER targeting and retention signals, 5′ and 3′ UTRs of arc5-1 gene along with CaMV 35S promoter, and then, transferred by Agrobacterium-mediated transformation. Gene and protein expression of hPDGF-BB were confirmed by PCR and immunoblot studies. Bioactivity of hPDGF-BB expressed protein was determined by in vitro assays such as proliferation and migration in NIH3T3 cells. Our data reveals that total soluble proteins containing hPDGF-BB from transgenic plants showed a 4.5-fold increase in fibroblast proliferation compared to non-transgenic plants. Furthermore, plant-made rhPDGF-BB induced chemotaxis of treated cells and promoted wound healing in vitro. These results clearly demonstrate that functionally active rhPDGF-BB protein can be produced in plants and might have therapeutic benefits.     

Induced fit process in the selective distal binding of imidazoles in zinc(II) porphyrin receptors

The respective affinities of various imidazole derivatives, imidazole (ImH), 2-methylimidazole (2-MeImH), 2-phenylimidazole (2-PhImH), N-methylimidazole (N-MeIm), 2-methylbenzimidazole (2-MeBzImH), and 4,5-dimethylbenzimidazole (4,5-Me(2)BzImH), for two phenanthroline (Phen) strapped zinc(II) porphyrin receptors porphen-Zn 1-Zn and 2-Zn have been studied. The formation of a supplementary H-bond considerably enhances the affinity of the zinc(II)-porphen receptor for imidazoles unsubstituted on the pyrrolic nitrogen (ImH) versus N-substituted imidazoles such as N-MeIm. The ImHs subset porphen-Zn complexes are formed with association constants up to 4 orders of magnitude superior to those measured either for N-MeIm as substrate or TPP-Zn as receptor. Distal or proximal binding of the substrates was determined by (1)H NMR measurements and titration. In two cases, the very high stability of the inclusion complex enabled the use of 2D NMR techniques. Excellent correlation between solution and solid-state structures has been obtained. A total of six X-ray structures are detailed in this article showing that the evolution of the shape of the zinc(II) receptor is mostly dependent on the steric constraints induced by the substitution on the imidazole. Hindered guests also progressively induce considerable mobility restrictions and severe distortions on the receptor, especially in the case of 2-MeBzImH and 2-PhImH.     

Colloidally Stable CdS Quantum Dots in Water with Electrostatically Stabilized Weak-Binding,Sulfur-Free Ligands

Colloidal quantum dot (QD) photocatalysts have the electrochemical and optical properties to be highly effective for a range of redox reactions. QDs are proven photo-redox catalysts for a variety of reactions in organic solvents but are less prominent for aqueous reactions. Aqueous QD photocatalysts require hydrophilic ligand shells that provide long-term colloidal stability but are not so tight-binding as to prevent catalytic substrates from accessing the QD surface. Common thiolate ligands, which also poison many co-catalysts and undergo photo-oxidative desorption, are therefore often not an option. This paper describes a framework for the design of water-solubilizing ligands that are in dynamic exchange on and off the QD surface, but still provide long-term colloidal stability to CdS QDs. The binding affinity and inter-ligand electrostatic interactions of a bifunctional ligand, aminoethyl phosphonic acid (AEP), are tuned with the pH of the dispersion. The key to colloidal stability is electrostatic stabilization of the monolayer. This work demonstrates a means of mimicking the stabilizing power of a thiolate-bound ligand with a zwitterionic tail group, but without the thiolate binding group.