Novel highly potent, structurally simple γ-trifluoromethyl γ-sulfone hydroxamate inhibitor of stromelysin-1 (MMP-3)

The γ-trifluoromethyl γ-sulfone hydroxamate 1 was synthesized both in racemic and enantiomerically pure forms by means of a thia-Michael reaction of p-methoxythiophenol on achiral and chiral 3,3,3-trifluorocrotonoyl Michael acceptors. The (R)-1 enantiomer was the most potent inhibitor of MMP-3 (stromelysin-1), showing an IC₅₀ = 3.2 nM, as well as the most selective with respect to MMP-9 (65-fold).     

Enhancing proline-rich antimicrobial peptide action by homodimerization: influence of bifunctional linker

Antimicrobial peptides (AMPs) are host defense peptides, and unlike conventional antibiotics, they possess potent broad spectrum activities and, induce little or no antimicrobial resistance. They are attractive lead molecules for rational development to improve their therapeutic index. Our current studies examined dimerization of the de novo designed proline-rich AMP (PrAMP), Chex1-Arg20 hydrazide, via C-terminal thiol addition to a series of bifunctional benzene or phenyl tethers to determine the effect of orientation of the peptides and linker length on antimicrobial activity. Antibacterial assays confirmed that dimerization per se significantly enhances Chex1-Arg20 hydrazide action. Greatest advantage was conferred using perfluoroaromatic linkers (tetrafluorobenzene and octofluorobiphenyl) with the resulting dimeric peptides 6 and 7 exhibiting potent action against Gram-negative bacteria, especially the World Health Organization''s critical priority-listed multidrug-resistant (MDR)/extensively drug-resistant (XDR) Acinetobacter baumannii as well as preformed biofilms. Mode of action studies indicated these lead PrAMPs can interact with both outer and inner bacterial membranes to affect the membrane potential and stress response. Additionally, 6 and 7 possess potent immunomodulatory activity and neutralise inflammation via nitric oxide production in macrophages. Molecular dynamics simulations of adsorption and permeation mechanisms of the PrAMP on a mixed lipid membrane bilayer showed that a rigid, planar tethered dimer orientation, together with the presence of fluorine atoms that provide increased bacterial membrane interaction, is critical for enhanced dimer activity. These findings highlight the advantages of use of such bifunctional tethers to produce first-in-class, potent PrAMP dimers against MDR/XDR bacterial infections.

Homodimerization of a proline-rich antimicrobial peptide via bioconjugation to perfluoroaromatic linkers confers increased antimicrobial, antibiofilm and immunomodulatory activity. The dimers are promising new therapeutic leads against WHO priority multidrug resistant bacteria.     

Incorporation of clay nano-particles in aqueous foams

During the process of crude oil/gasoline loading and storage, significant amounts of volatile organic compounds (VOCs) can be emitted to the environment. Stable aqueous foams can be spread as a flexible blanket on the top of the oil to control the VOC emission by providing a mass transfer barrier during the loading process. In this work, novel aqueous foams have been formulated by incorporating clay nano-particles in an aqueous solution of surfactants and polymers. The stability and mass transfer resistance of these foams were investigated at temperatures up to 125 F. In the presence of VOC, clay decreases the rate at which the liquid is drained out of the foam lamellae and increases the foam drainage half-life. These foams were found to be very stable in the presence of gasoline and crude oil and can last much longer than one day at the room temperature. The use of clay in the foam formulation reduces vapor diffusion through the lamellae and vapor emission through the foam column significantly for the first 10 h. Increase in temperature increases the rate of foam breakage due to higher water evaporation and lower liquid viscosity. In spite of this increase, the 0.5% polymer and 0.5% clay foam suppresses vapor emission from a gasoline longer than 3600, 1500 and 1100 min at 75 F, 105 F and 125 F, respectively. This foam also suppresses vapor emission from a crude oil longer than 4200, 2000 and 700 min at 75 F, 105 F and 125 F, respectively.     

Organic-ligand-assisted supercritical hydrothermal synthesis of titanium oxide nanocrystals leading to perfectly dispersed titanium oxide nanoparticle in organic phase

Titanium oxide (TiO₂) nanocyrstals which are perfectly dispersed in organic solvents are synthesized by organic-ligand-assisted supercritical hydrothermal synthesis. The addition of hexaldehyde to the supercritical hydrothermal synthesis of TiO₂ leads to the in-situ surface modification, which enables the synthsized TiO₂ nanocrystals to be perfectly dispersed in iso-octane because of its hydrophobic nature. Further, the one-pot synthesis of hybrid materials results in the significant reduction of the particles size, probably due to the capping effect of hexaldehyde to suppress the particles growth.     

The implementation of normal and/or tangential boundary conditions in finite element codes for incompressible fluid flow

Various techniques for implementing normal and/or tangential boundary conditions in finite element codes are reviewed. The principle of global conservation of mass is used to define a unique direction for the outward pointing normal vector at any node on an irregular boundary of a domain containing an incompressible fluid. This information permits the consistent and unambiguous application of essential or natural boundary conditions (or any combination thereof) on the domain boundary regardless of boundary shape or orientation with respect to the co-ordinate directions in both two and three dimensions. Several numerical examples are presented which demonstrate the effectiveness of the recommended technique.     

Antimicrobial activity of nanocellulose conjugated with allicin and lysozyme

In this study, cellulose nanoparticles were prepared by acid hydrolysis, separately conjugated with allicin and lysozyme by a carbodiimide cross-linker, and characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. Then, their antimicrobial properties were evaluated by the microdilution method and compared with allicin, lysozyme, and nanocellulose alone. The results showed that nanocellulose had few antimicrobial activities, but allicin-conjugated nanocellulose (ACNC) and lysozyme-conjugated nanocellulose (LCNC) had good antifungal and antibacterial effects against standard strains of Candida albicans, Aspergillus niger, Staphylococcus aureus, and Escherichia coli. Noticeably, although allicin and lysozyme had different minimum inhibitory concentrations (MICs) against all strains, the same quantity of MIC₅₀ and MIC₉₀ was observed for both ACNC and LCNC. The authors suggest that both ACNC and LCNC can be used in industries as an antimicrobial agent in food packaging, inside foodstuffs, and in textile materials.