A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific,On-Resin Ozonolysis to Install the Kynurenine Residue

A de novo solid-phase synthesis of the cyclic lipodepsipeptide daptomycin via Boc chemistry was achieved. The challenging ester bond formation between the nonproteinogenic amino acid kynurenine was achieved by esterification of a threonine residue with a protected tryptophan. Subsequent late-stage on-resin ozonolysis, inspired by the biomimetic pathway, afforded the kynurenine residue directly. Synthetic daptomycin possessed potent antimicrobial activity (MIC₁₀₀=1.0 μg mL⁻¹) against S. aureus, while five other daptomycin analogues containing (2R,3R)-3-methylglutamic acid, (2S,4S)-4-methylglutamic acid or canonical glutamic acid at position twelve prepared using this new methodology were all inactive, clearly establishing that the (2S,3R)-3-methylglutamic acid plays a key role in the antimicrobial activity of daptomycin.     

The simulation of oscillatory pipe flow on an analogue computer

Summary A formulation of equations governing oscillatory flow of a fluid in a circular pipe is given. The equations are then cast in a form suitable for analogue computation and a corresponding programming diagram suitable for use with an EAI 680 Analogue Computer is provided. Results have been obtained forNewtonian flow for a range ofReynolds numbers and for combinations of the realReynolds number, and the ratio of elastic to viscous forces in the case of linear viscoelastic fluids.The displacement profiles given in this work do not depend upon specific rheological models and are therefore of universal validity for linear fluids.     

Review on penetration and transport phenomena in porous media during slot die coating

A distinctive field in the coatings industry is coating of porous media, which has broad applications including paper, textiles, electronics, filtration, and energy sectors. Fluid penetration is an important issue during direct coating of a liquid bead on porous media, which is driven by the pressure from an external flow field and the surface tension in the porous media. Generally, during the coating process, some level of penetration is desirable to obtain specific material properties, but inadequate or excessive penetration is detrimental. To help control the level of penetration, understanding relationships between operating parameters and penetration are highly desirable. In this article, the current state of academic research on modeling penetration in porous media during common coating processes, especially the slot die coating process, is reviewed. Specifically, the challenges, basic ideas, advantages, and disadvantages of macroscale, microscale, and pore-network models on penetration in porous media are discussed. This article concludes with some recommendations for future work. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1669–1680     

Fractal based observables to probe jet substructure of quarks and gluons

New jet observables are defined which characterize both fractal and scale-dependent contributions to the distribution of hadrons in a jet. These infrared safe observables, named Extended Fractal Observables (EFOs), have been applied to quark–gluon discrimination to demonstrate their potential utility. The EFOs are found to be individually discriminating and only weakly correlated to variables used in existing discriminators. Consequently, their inclusion improves discriminator performance, as here demonstrated with particle level simulation from the parton shower.     

The Effect of Gadolinium Doping in [13C6,2H7]Glucose Formulations on 13C Dynamic Nuclear Polarization at 3.35 T

The promise of hyperpolarized glucose as a non-radioactive imaging agent capable of reporting on multiple metabolic routes has led to recent advances in its dissolution-DNP (dDNP) driven polarization using UV-light induced radicals and trityl radicals at high field (6.7 T) and 1.1 K. However, most preclinical dDNP polarizers operate at the field of 3.35 T and 1.4–1.5 K. Minute amounts of Gd³⁺ complexes have shown large improvements in solid-state polarization, which can be translated to improved hyperpolarization in solution. However, this Gd³⁺ effect seems to depend on magnetic field strength, metal ion concentration, and sample formulation. The effect of varying Gd³⁺ concentrations at 3.35 T has been described for ¹³C-labeled pyruvic acid and acetate. However, it has not been studied for other compounds at this field. The results presented here suggest that Gd³⁺ doping can lead to various concentration and temperature dependent effects on the polarization of [¹³C₆,²H₇]glucose, not necessarily similar to the effects observed in pyruvic acid or acetate in size or direction. The maximal polarization for [¹³C₆,²H₇]glucose appears to be at a Gd³⁺ concentration of 2 mM, when irradiating for more than 2 h at the negative maximum of the DNP intensity profile. Surprisingly, for shorter irradiation times, higher polarization levels were determined at 1.50 K compared to 1.45 K, at a [Gd³⁺]=1.3 mM. This was explained by the build-up time constant and maximum at these temperatures.     

Localized hydrogels based on cellulose nanofibers and wood pulp for rapid removal of methylene blue

Access to clean water has become increasingly difficult, motivating the need for materials that can efficiently remove pollutants. Hydrogels have been explored for remediation, but they often require long times to reach high levels of adsorption. To overcome this limitation, we developed a rapid, locally formed hydrogel that adsorbs dye during gelation. These hydrogels are derived from cellulose—a renewable, nontoxic, and biodegradable resource. More specifically, we found that sulfated cellulose nanofibers or sulfated wood pulps, when mixed with a water-soluble, cationic cellulose derivative, efficiently remove methylene blue (a cationic dye) within seconds. The maximum adsorption capacity was found to be 340 ± 40 mg methylene blue/g cellulose. As such, these localized hydrogels (and structural analogues) may be useful for remediating other pollutants.     

Boron–Nitrogen-Doped Nanographenes: A Synthetic Tale from Borazine Precursors

In this work, a comprehensive account of the authors’ synthetic efforts to prepare borazino-doped hexabenzocoronenes by using the Friedel–Crafts-type electrophilic aromatic substitution is reported. Hexafluoro-functionalized aryl borazines, bearing an ortho fluoride leaving group on each of the N- and B-aryl rings, was shown to lead to cascade-type electrophilic aromatic substitution events in the stepwise C−C bond formation, giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at the ortho positions of the B-aryl substituents. By using this pathway, an unprecedented boroxadizine-doped PAH featuring a gulf-type periphery could be isolated, and its structure proven by single-crystal X-ray diffraction analysis. Mechanistic studies on the stepwise Friedel–Crafts-type cyclization suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology-equivalent molecular graphenes, the all-carbon and pyrylium PAH analogues, all featuring a gulf-type periphery, were also prepared. As already shown for the borazino-doped hexabenzocoronene, the replacement of the central benzene ring by its B₃N₂O congener widens the HOMO–LUMO gap and dramatically enhances the fluorescence quantum yield.     

Redox Stability Controls the Cellular Uptake and Activity of Ruthenium-Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)

The mitochondrial calcium uniporter (MCU) is the ion channel that mediates Ca²⁺ uptake in mitochondria. Inhibitors of the MCU are valuable as potential therapeutic agents and tools to study mitochondrial Ca²⁺. The best-known inhibitor of the MCU is the ruthenium compound Ru360. Although this compound is effective in permeabilized cells, it does not work in intact biological systems. We have recently reported the synthesis and characterization of Ru265, a complex that selectively inhibits the MCU in intact cells. Here, the physical and biological properties of Ru265 and Ru360 are described in detail. Using atomic absorption spectroscopy and X-ray fluorescence imaging, we show that Ru265 is transported by organic cation transporter 3 (OCT3) and taken up more effectively than Ru360. As an explanation for the poor cell uptake of Ru360, we show that Ru360 is deactivated by biological reductants. These data highlight how structural modifications in metal complexes can have profound effects on their biological activities.