Particle Adhesion to Drops

The adhesion of spheroidal particles to spherical drops is calculated and discussed in terms of an equilibrium-penetration index. The present study emphasizes the case of particles that are sufficiently large to affect the drop volume upon penetration. It is shown that the more elongated the particles, the steeper the dependence of the penetration index on the contact angle. The effect of line tension on nanoscale particles is considered. Positive line tensions increase the steepness of the dependence of penetration index on contact angle whereas negative line tensions decrease this dependence. In addition, the energy barrier caused by positive line tensions is presented and discussed.     

Development and Validation of an Artificial Mechanical Skin Model for the Study of Interactions between Skin and Microneedles

Microneedles are small needle‐like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major difficulty with understanding the mechanism of microneedle–skin interaction is the lack of an artificial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artificial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artificial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.

     

Synthesis of cross‐linked polyethylene oxide‐acetal macrocycles for solid superbase catalysts

A novel long‐chain divinyl ether of tris(diethyleneglycol)‐bisacetal, has been synthesized by electrophilic addition of one molecule of diethylene glycol to two molecules of divinyl ether of diethylene glycol (DVDEG) in the presence of CF₃COOH in quantitative yield. The monomer was cationically polymerized (BF₃·OEt₂, or complex LiBF₄·MeO(CH₂)₂OMe) and copolymerized with DVDEG to deliver solid polymers the yields being 80–100%. The polymers represent the cross‐linked polyether‐polyacetal structures comprising macrocycles. The polymers were treated with 3% solution of KOH or CsOH in methanol to afford solid superbase complexes of KOH (CsOH) with cross‐linked polyether‐polyacetal macrocyclic networks. Preliminary tests have shown the complexes to be active catalysts for ethynylation of acetones and prototropic isomerization of methyl propargyl ethers to allenyl methyl ethers. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Methods and Applications of In Silico Aptamer Design and Modeling

Aptamers are nucleic acid analogues of antibodies with high affinity to different targets, such as cells, viruses, proteins, inorganic materials, and coenzymes. Empirical approaches allow the design of in vitro aptamers that bind particularly to a target molecule with high affinity and selectivity. Theoretical methods allow significant expansion of the possibilities of aptamer design. In this study, we review theoretical and joint theoretical-experimental studies dedicated to aptamer design and modeling. We consider aptamers with different targets, such as proteins, antibiotics, organophosphates, nucleobases, amino acids, and drugs. During nucleic acid modeling and in silico design, a full set of in silico methods can be applied, such as docking, molecular dynamics (MD), and statistical analysis. The typical modeling workflow starts with structure prediction. Then, docking of target and aptamer is performed. Next, MD simulations are performed, which allows for an evaluation of the stability of aptamer/ligand complexes and determination of the binding energies with higher accuracy. Then, aptamer/ligand interactions are analyzed, and mutations of studied aptamers made. Subsequently, the whole procedure of molecular modeling can be reiterated. Thus, the interactions between aptamers and their ligands are complex and difficult to understand using only experimental approaches. Docking and MD are irreplaceable when aptamers are studied in silico.     

Aryl Bis‐Sulfonamide Inhibitors of IspF from Arabidopsis thaliana and Plasmodium falciparum

2‐Methylerythritol 2,4‐cyclodiphosphate synthase (IspF) is an essential enzyme for the biosynthesis of isoprenoid precursors in plants and many human pathogens. The protein is an attractive target for the development of anti‐infectives and herbicides. Using a photometric assay, a screen of 40 000 compounds on IspF from Arabidopsis thaliana afforded symmetrical aryl bis‐sulfonamides that inhibit IspF from A. thaliana (AtIspF) and Plasmodium falciparum (PfIspF) with IC₅₀ values in the micromolar range. The ortho‐bis‐sulfonamide structural motif is essential for inhibitory activity. The best derivatives obtained by parallel synthesis showed IC₅₀ values of 1.4 μm against PfIspF and 240 nm against AtIspF. Substantial herbicidal activity was observed at a dose of 2 kg ha^?1. Molecular modeling studies served as the basis for an in silico search targeted at the discovery of novel, non‐symmetrical sulfonamide IspF inhibitors. The designed compounds were found to exhibit inhibitory activities in the double‐digit micromolar IC₅₀ range.     

Absorption and reflection of infrared radiation by polymers in fire‐like environments

In large‐scale fires, the input of energy to burning materials occurs predominantly by radiative transfer. The in‐depth (rather than just surface) absorption of radiant energy by a polymer influences its ignition time and burning rate. The present investigation examines two methods for obtaining the absorption coefficient of polymers for infrared radiation from high‐temperature sources: a broadband method and a spectral method. Data on the total average broadband transmittance for 11 thermoplastics are presented (as are reflectance data), and the absorption coefficient is found to vary with thickness. Implications for modeling of mass loss experiments are discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

Switching azonaphthols containing a side chain with limited flexibility. Part 1. Synthesis and tautomeric properties

A series of azo dyes, possessing amide fragments with restricted flexibility tethered to 4-(phenyldiazenyl)naphthalen-1-ol, was obtained from 1-hydroxy-2-naphthoic acid by subsequent conversion to amides and diazo coupling. It was shown that the position of the tautomeric equilibrium in solution strongly depends on the solvent in both UV and NMR concentration scale. The compounds exist as pure enol forms in chloroform and hydrocarbons, while in polar solvents (acetone, acetonitrile, alcohols) a tautomeric mixture is observed. According to the quantum-chemical calculations the aggregation of the keto tautomer is the possible reason for this shift in the position of the tautomeric equilibrium. To support the theoretical predictions, it was found that from acetone the keto form crystallizes as a dimer with hydrogen bonding between N₁-H in the one molecule and amide CO in the other forming a three-dimensional structure. The importance of the side-chain nitrogen atom on the dimer formation was confirmed by solution and solid state study of 4-(phenyldiazenyl)-2-acetylnaphthalen-1-ol. The results indicate that the new azo-dyes obtained could be suitable candidates for switching and sensing applications in non-polar solvents.     

Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit

The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.     

Reduction in internal friction in silica glass with high OH content

The aim of this article was to investigate processes occurring during annealing of silica glass classified as being of type III (J Non Cryst Solids. 1970;5(2):123-75). This is an inexpensive silica glass produced by many manufacturers across the globe. However, it can be successfully used for fabrication of high-Q mechanical resonators. The relationship between residual internal stress and internal friction is elucidated. Quantitative analysis of the structural relaxation kinetics is presented. The influence of the cooling process for structural transformation is also discussed. On the basis of our results, we suggest optimal annealing conditions for minimizing internal friction type III silica glass. The results will be useful for further improvement of the Q-factor of mechanical resonators, including the test masses of the next generation of gravitational wave detectors. Our approach might, in addition, be used for studying the modification of atomic structure in multicomponent glasses.