Copper-free click conjugation of methotrexate to a PAMAM dendrimer platform

The synthesis of a generation 5 (G5) poly(amidoamine) (PAMAM) dendrimer platform having cyclooctyne ligands that were subsequently be used for a copper-free Huisgen 1,3-dipolar cycloaddition (click reaction) with azido modified methotrexate is described. The G5 PAMAM dendrimer was first partially (70%) acetylated and then coupled with 20 cyclooctyne ligands through amide bonds. The remaining primary amine groups on the dendrimer surface were neutralized by acetylation. The platform was then ‘clicked’ with different numbers (5, 10, and 17) of γ-azido functionalized methotrexate. The copper-free click reactions were stoichiometric with excellent yields.     

Development of double cylindrical dielectric barrier discharge ion source

This paper deals with the dielectric barrier discharge (DBD) ion source composed of the outer cylindrical dielectric tube and the inner grounded metallic tube electrode. The sample gas is supplied through the inner ceramic tube. In this ion source, the DBD plasma is localized in the DBD tube so that the sample gases can be ionized just outside of the ceramic tube by the DBD excited helium gas without being exposed in the plasma jet. Besides, ambient air does not take part in the ionization of the sample vapor because ionization takes place inside the DBD ion source. Thus, this method is totally free from contaminants in ambient air. It was found that this ion source is capable of soft, high-sensitivity, and reproducible ionization. Application of this technique to the analysis of methamphetamine, carbaryl and basil leaf was given.     

One‐Pot,Three‐Component Synthesis of Novel Spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones in an Ionic Liquid as a Reusable Reaction Media

A facile one‐pot, three‐component protocol for the synthesis of novel spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones by condensing 1H‐indole‐2,3‐diones, 4H‐1,2,4‐triazol‐4‐amine and 2‐sulfanylpropanoic acid in [bmim]PF₆ (1‐butyl‐3‐methyl‐1H‐imidazolium hexafluorophosphate) as a recyclable ionic‐liquid solvent gave good to excellent yields in the absence of any catalyst (Scheme 1 and Table 2). The advantages of this protocol over conventional methods are the mild reaction conditions, the high product yields, a shorter reaction time, as well as the eco‐friendly conditions.     

Dynamic Coupling at the Ångström Scale

While momentum transfer from active particles to their immediate surroundings has been studied for both synthetic and biological micron‐scale systems, a similar phenomenon was presumed unlikely to exist at smaller length scales due to the dominance of viscosity in the ultralow Reynolds number regime. Using diffusion NMR spectroscopy, we studied the motion of two passive tracers—tetramethylsilane and benzene—dissolved in an organic solution of active Grubbs catalyst. Significant enhancements in diffusion were observed for both the tracers and the catalyst as a function of reaction rate. A similar behavior was also observed for the enzyme urease in aqueous solution. Surprisingly, momentum transfer at the molecular scale closely resembles that reported for microscale systems and appears to be independent of swimming mechanism. Our work provides new insight into the role of active particles on advection and mixing at the Ångström scale.     

On the Mechanism of Copper(I)‐Catalyzed Azide–Alkyne Cycloaddition

The copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4‐disubstituted‐1,2,3‐triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring‐formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pK_a values and an inclination to engage in π‐backbonding with copper(I), azides with ancillary copper‐binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne‐involved CuAAC reactions are also included, based on the relatively limited data that are available at this point.     

In vitro nonenzymatic glycation of DNA nucleobases: an evaluation of advanced glycation end products under alkaline pH

The advanced glycation end products (AGEs) of DNA nucleobases have received little attention, perhaps due to the fact that adenine, guanine, cytosine and thymine do not dissolve under mild pH conditions. To maintain nucleobases in solution, alkaline pH conditions are typically required. The objectives of this investigation were twofold: to study the susceptibility of DNA nucleobases to nonenzymatic attack by different sugars, and to evaluate the factors that influence the formation of nucleobase AGEs at pH 12, i.e., in an alkaline environment that promotes the aldo–keto isomerization and epimerization of sugars. Varying concentrations of adenine, guanine, thymine and cytosine were incubated over time with constant concentrations of D-glucose, D-galactose or D/L-glyceraldehyde under different conditions of temperature and ionic strength. Incubation of the nucleobases with the sugars resulted in a heterogeneous assembly of AGEs whose formation was monitored by UV/fluorescence spectroscopy. Capillary electrophoresis and HPLC were used to resolve the AGEs of the DNA adducts and provided a powerful tool for following the extent of glycation in each of the DNA nucleobases. Mass spectrometry studies of DNA adducts of guanine established that glycation at pH 12 proceeded through an Amadori intermediate.     

Patterning porous matrices and planar substrates with quantum dots

Silica hydrogels and planar substrates were patterned with CdS nanoparticles using a photolithographic method based on the photo dissociation of thiols and cadmium-thiolate complexes. Silica hydrogels were prepared via a standard base-catalyzed route. The solvent was exchanged with an aqueous solution of CdSO₄ and 2-mercaptoethanol, and the samples were then exposed to a focused ultraviolet beam. Planar substrates were patterned by illuminating a precursor solution spin coated on the substrates. CdS nanoparticles formed in the illuminated spots, and had a diameter below about 2 nm. The diameter of the spots illuminated by the UV beam could be varied from a few hundred to a few μm, on both hydrogels and planar substrates. Samples were characterized with transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, and optical absorption, photoluminescence and Raman spectroscopies. All these techniques confirmed the chemical identity of the CdS nanoparticles. To investigate the mechanism of nanoparticle formation, we took absorption spectra of the precursor solution as a function of irradiation time. In unirradiated solutions, we noticed a maximum at 250 nm, characteristic of Cd-thiolate complexes. The absorption at 250 nm decreased with increasing irradiation time. A new band appeared at 265 nm for exposures around 5 min, and that band shifted to 290 nm in samples exposed for 10 min. A yellow precipitate formed after about 30 min. XRD showed that the precipitate was cubic CdS, with a mean particle size of 1.4 nm. We attribute formation of CdS to the photodissociation of the thiols and of the Cd-thiolates. UV irradiation of these precursors yields a series of species that can react with Cd²⁺, such as RS^·, S²⁻ and H₂S. Small CdS nanoparticles form in the initial stages of illumination, and present absorption bands in the 265–290 nm region. These CdS aggregates grow, coalesce and precipitate for longer irradiation times.     

Synthesis and DNA binding properties of pyrrole amino acid-containing peptides

Dimers of the pyrrole amino acid (Paa), 5-(aminomethyl)pyrrole-2-carboxylic acid, and its derivatives having Lys anchored on N- and C-termini bind in the minor groove of DNA with considerable apparent binding affinities. When the Lys unit is attached to the C-terminus, the resulting ligand binds to ds-DNA with twice the affinity, of the order of 10⁵, than the one carrying two positive charges at the same end.     

Application of directed metalation in synthesis. Part 7: Synthesis of suitably functionalised benzo[b]thiophenes as key intermediates in the synthesis of benzothienopyranones

One-pot syntheses of (3-hydroxybenzo[b]thiophen-2-yl) aryl methanones from ortho-methylsulfanylaryl N,N-diethyl amides and of 1-(3-hydroxybenzo[b]thiophen-2-yl)ethanone and 1-(3-hydroxybenzo[b]thiophen-2-yl)propan-1-one via an anionic ortho-Fries rearrangement are described. The hydroxy ketones were used as key intermediates in the synthesis of benzothienopyranones.     

Recombination reactions of oxygen atoms on an anodized aluminum plasma reactor wall, studied by a spinning wall method

We have studied the recombination of O atoms on an anodized Al surface in an oxygen plasma, using a new "spinning wall" technique. With this method, a cylindrical section of the wall of the plasma reactor is rotated and the surface is periodically exposed to an oxygen plasma and then to a differentially pumped mass spectrometer (MS). By varying the substrate rotation frequency (r), we vary the reaction time (t(r)), that is, the time between exposure of the surface to O atoms in the plasma and MS detection of desorbing O(2) (t(r) = 1/2r). As t(r) is increased from 0.7 to 40 ms, the O(2) desorption signal decreases by a factor of 2 for an O-atom flux of 1 x 10(16) cm(-2) s(-1) and by a factor of 6 when the O flux is 1 x 10(17) cm(-2) s(-1). The O(2) signal decay is highly nonexponential, slowing at longer times and reaching zero signal as r --> 0. A model of O-atom recombination is compared with these time-dependent results. The model assumes adsorption occurs at surface sites with a range of binding energies. O can detach from these sites, become mobile, and diffuse along the surface. This leads to desorption of O, reattachment at free adsorption sites, and recombination to form O(2) that promptly desorbs. With several adjustable parameters, the model reproduces the observed shapes of the O(2) desorption decay curves and the lack of detectable desorption of O and predicts a high O-atom recombination coefficient on anodized aluminum.