Development and Validation of a High-Performance Thin-Layer Chromatographic Method,with Densitometry,for Quantitative Analysis of Tizoxanide (a Metabolite of Nitazoxanide) in Human Plasma

JPC – Journal of Planar Chromatography – Modern TLC - A new simple, rapid, and selective high-performance thin-layer chromatographic (HPTLC) method with metronidazole as the internal...     

Suppressing the environmental dependence of the open‐circuit voltage in inverted polymer solar cells through a radical polymer anodic modifier

Developing stable, readily‐synthesized, and solution‐processable transparent conducting polymers for interfacial modifying layers in organic photovoltaic (OPV) devices has become of great importance. Here, the radical polymer, poly(2,2,6,6‐tetramethylpiperidinyloxy methacrylate (PTMA), is shown to not affect the absorption of the well‐studied poly(3‐hexylthiophene) (P3HT) and [6,6]‐phenyl‐C₆₁‐butyric acid methyl ester (PCBM) active layer when incorporated into inverted OPV devices, as it is highly transparent in the visible spectrum due to the non‐conjugated nature of the PTMA backbone. The inclusion of this radical polymer as an anode‐modifying layer enhanced the open‐circuit voltage and short‐circuit current density values over devices that did not contain an anodic modifier. Importantly, devices fabricated with the PTMA interlayer had performance metrics that were time‐independent over the entire course of multiples days of testing after exposing the OPV devices to ambient conditions. Furthermore, these high performance values were independent of the metal used as the top electrode contact in the inverted OPV devices. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 311–316     

Cell compatible trimethoprim-decorated iron oxide nanoparticles bind dihydrofolate reductase for magnetically modulating focal adhesion of mammalian cells

On the basis of the high affinity binding of trimethoprim (TMP) to Escherichia coli dihydrofolate reductase (eDHFR), TMP-decorated iron oxide nanoparticles bind to eDHFR with high affinity and specificity, which allows magnetic modulation of focal adhesion of mammalian cells adhered to a surface. Besides being the first example of nanoparticles that selectively bind to eDHFR, the biocompatibility of the conjugate of TMP-iron oxide nanoparticles renders a convenient and versatile platform for investigating the cellular responses to specific, mechanical perturbation of proteins via a magnetic force.     

Inhibitor mediated protein degradation

The discovery of drugs that cause the degradation of their target proteins has been largely serendipitous. Here we report that the tert-butyl carbamate-protected arginine (Boc(3)Arg) moiety provides a general strategy for the design of degradation-inducing inhibitors. The covalent inactivators ethacrynic acid and thiobenzofurazan cause the specific degradation of glutathione-S-transferase when linked to Boc(3)Arg. Similarly, the degradation of dihydrofolate reductase is induced when cells are treated with the noncovalent inhibitor trimethoprim linked to Boc(3)Arg. Degradation is rapid and robust, with 30%-80% of these abundant target proteins consumed within 1.3-5 hr. The proteasome is required for Boc(3)Arg-mediated degradation, but ATP is not necessary and the ubiquitin pathways do not appear to be involved. These results suggest that the Boc(3)Arg moiety may provide a general strategy to construct inhibitors that induce targeted protein degradation.     

Comparison of the thermal decomposition behavior for members of the hydroxylamine family

In the present work the thermal stability of some members of the hydroxylamine family was studied using adiabatic calorimetry. The study included aqueous solutions of hydroxylamine free base, hydroxylamine hydrochloride, hydroxylamine sulfate, and hydroxylamine-o-sulfonic acid of concentrations typically used in industry. Also, the catalytic effect of metal surfaces of stainless steel, carbon steel, and titanium was studied. From the solutions studied HA is the most reactive with higher maximum temperature, pressure, non-condensable pressure, and lower time to maximum rate. HA maximum heat rate is at least ∼3 times higher than that of the other solutions studied, and the pressure generation rate is ∼13 times higher. All decompositions were catalyzed by stainless steel, but only HA was catalyzed significantly by titanium metal. Solid hydroxylamine hydrochloride, hydroxylamine sulfate, and hydroxylamine-o-sulfonic acid exhibited stability up to ∼60 °C. Hydroxylamine 100% was not studied because it is not readily available, is not used industrially, and is known to be unstable at room temperature. A violent reaction was measured for solid hydroxylamine sulfate that generated a heat rate >500 °C/min and pressure rate >5200 psia/min before the sample cell was completely destroyed by the generated pressure.     

Development and Validation of a Densitometric HPTLC Method for Quantitative Analysis of Levofloxacin in Human Plasma

JPC – Journal of Planar Chromatography – Modern TLC -     

Preparation of stimuli-responsive nanogels based on poly(N,N-diethylaminoethyl methacrylate) by a simple “surfactant-free” methodology

The synthesis of poly(N,N-diethylaminoethyl methacrylate)-core-polyethyleneglycol-shell (PDEAEM-core-PEG-shell) nanogels was achieved by using a “surfactant-free” emulsion polymerization with the aid of commercially available polyethyleneglycol methyl ether methacrylates (PEGMAs) as polymerizable stabilizers. By adjusting the synthetic parameters like the choice of initiator, cross-linker, PEGMA:DEAEM ratio, and molecular weight of PEGMA, a series of core-shell nanogels varying in size (50–350 nm), PDEAEM content, and pH/temperature responsive behavior were obtained in reactions taking only 60 min. The nanogels were used as nanoreactors for the preparation of gold nanoparticles. The PEGylated nanogels have a great potential to be used for diagnosis and therapy.     

Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases

The protozoan parasite Cryptosporidium parvum is a major cause of gastrointestinal disease; no effective drug therapy exists to treat this infection. Curiously, C. parvum IMPDH (CpIMPDH) is most closely related to prokaryotic IMPDHs, suggesting that the parasite obtained its IMPDH gene via horizontal transfer. We previously identified inhibitors of CpIMPDH that do not inhibit human IMPDHs. Here, we show that these compounds also inhibit IMPDHs from Helicobacter pylori, Borrelia burgdorferi, and Streptococcus pyogenes, but not from Escherichia coli. Residues Ala165 and Tyr358 comprise a structural motif that defines susceptible enzymes. Importantly, a second-generation CpIMPDH inhibitor has bacteriocidal activity on H. pylori but not E. coli. We propose that CpIMPDH-targeted inhibitors can be developed into a new class of antibiotics that will spare some commensal bacteria.     

Using supramolecular hydrogels to discover the interactions between proteins and molecular nanofibers of small molecules

Here we report the first example of the use of supramolecular hydrogels to discover the protein targets of aggregates of small molecules.     

On compactness and cocompactness conditions for R-tors,R-pr and (big) lattices of classes of modules

We study conditions related to compactness and cocompactness for some (big) lattices of classes of modules and preradicals. Also, we give some characterizations in terms of rings and modules.