1,3-Dipolar character of 2-vinyl quinazoline 3-oxides; first and second generation cycloaddition products

The reaction between the heteroaromatic N-oxides 1a, 1b and 1c with dimethyl acetylenedicarboxylate or methyl propiolate furnishes 1,3-benzodiazepines, the products of ring transformations of primarily formed cycloadducts. The structures of 8a and 10a have been confirmed by X-ray crystallographic analysis. The aldonitrone 1c also reacts with N-methylmaleimide and with phenyl vinyl sulfone to furnish the first examples of primary cycloaddition products from quinazoline 3-oxides.     

The dihydrofuran template approach to furofuran synthesis

Flash vacuum pyrrolysis of vinyl epoxides provides cis-dihydrofuran carboxylic esters in good yields and diastereoselectivities, which, on base-promoted epimerisation afford the complementary trans series. The compounds provide a viable template for a Lewis acid promoted cyclisation to provide the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane core found in the furofuran series of natural lignans. This strategy is stereodivergent and can be controlled to provide the exo-exo, exo-endo or endo-endo stereochemistries. The approach has been exemplified in syntheses of the sesamyl furofurans (+/-)-epiasarinin and (+/-)-asarinin.     

High-resolution IR cavity ring-down spectroscopy of jet-cooled free radicals and other species

Initial spectral results are reported from a newly constructed cavity ringdown spectrometer. The apparatus incorporates a slit-jet expansion, with or without a discharge, to produce cold sample molecules. High spectral resolution in both the near- and mid-IR is obtained by using stimulated Raman scattering of the pulsed amplified output of a cw Ti:Sa ring laser. Molecular spectra presented include the electronic near-IR transitions a (1)Delta(g)(-)<-- X (3)Sigma(g)(-) of O(2) and B (3)Pi(g)<-- A (3)Sigma(u)(+) of metastable N(2) and vibrational overtones of H(2)O (polyad 2) and the OH radical. Fundamental vibrational transitions of CH(3) (nu(3)) in the mid-IR are also observed. This apparatus has demonstrated the potential for obtaining high-resolution spectra of both reactive and non-reactive species throughout the entire IR region.     

PAMAM dendrimers for efficient siRNA delivery and potent gene silencing

Genuine, nondegraded PAMAM dendrimers self-assemble with siRNA into nanoscale particles that are efficient for siRNA delivery and induce potent endogenous gene silencing.     

Spatiotemporal dynamics of the Landolt reaction in an open spatial reactor with conical geometry

In a previous study, the iodate-sulfite proton autoactivated reaction (Landolt reaction) was shown to exhibit spatial bistability and spatiotemporal oscillations when operated in an open spatial reactor with fixed "thickness", i.e., feed boundary to core distance. Here, we show that the spatial reactors with conical geometry enable one to rapidly probe the sensitivity of the above phenomena over a large range of the "thickness" parameter. This often-neglected parameter in chemical pattern studies plays an important role on the selection and stability of states. We reveal that the quenching capacity of slow diffusing polyacrylate ions on the spatiotemporal oscillations depends on this "thickness". The presented results should be useful for further research on reaction diffusion patterns and chemomechanical structures.     

Analysing the output from primary screening

From a perspective of process knowledge and enhancement, the analysis of the results of biological screening should not be limited to the outcome of specific projects, but additionally encompass a process centric view. Summarising outcomes across multiple projects is a powerful tool to gain a greater understanding of biological screening that will also enable optimisation of the strategy for specific projects or target classes. We have analysed a set of 73,651 compounds with reproducible (confirmed) results from 63 high-throughput screening (HTS) campaigns to reveal the underlying trends in the population of active compounds. We have focused on the overall physico-chemical profile of compound populations derived from biological screening since the in vivo activity of drug molecules is the result of physico-chemical and structural properties of the compound.