Bright molecules with sense, logic, numeracy and utility

Using cartoons as an organizational aid, we illustrate how the 'fluorophore-spacer-receptor' format of fluorescent PET (photoinduced electron transfer) sensors and switches can be logically extended in many different directions. These include emissive sensors for various chemical species and properties, and exploit various kinds of emission. Common sensing issues such as dynamic range, internal referencing, selectivity, mapping and space resolution are addressed. The sensory output function is also developed into more complex forms, molecular logic/computation being one such example. Molecular logic leads to molecular arithmetic. Real-life applications to physiological monitoring, medical diagnostics and molecular computational identification of small objects are included.     

Regiospecific beta-functionalization of free-base porphyrins by pseudohalogens

Pseudohalogens based on iodine ('I-X') can be used to regiospecifically introduce chlorine atoms or acetoxy groups onto the beta-positions of meso-tetraphenylporphyrins (TPPs). TPPs and a quinoxaline derivative were reacted with iodine monochloride to give mono- or di-chlorinated porphyrins, such that when two chlorine atoms were added they were placed antipodally on the porphyrin ring. Reaction of the porphyrins with a mixture of iodine and silver acetate gave the corresponding mono- and di-acetoxylated porphyrins. The acetoxylated porphyrins could be simply transformed to the corresponding hydroxyporphyrins with subsequent oxidation with the Dess-Martin periodinane, giving a simple new route to chlorin-alpha-diones and bacteriochlorin-tetraones. From the products of the reactions and a UV-visible spectroscopic study, it is proposed that the reactions proceed via a single electron transfer mechanism through a porphyrin cation radical intermediate.     

Estimating protein-ligand binding affinity using high-throughput screening by NMR

Many of today's drug discovery programs use high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or line width to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR screens that use 1D (1)H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA.     

Fabrication of polymer microsphere particle standards containing trace explosives using an oil/water emulsion solvent extraction piezoelectric printing process

We present a methodology for fabricating polymer microspheres using inkjet printing of a biodegradable polymer containing either high explosives or high explosive simulant. Poly(dl-lactide/glycolide) 85:15 (PLGA) microsphere production is based on an oil/water emulsion solvent extraction process. The inkjet printing process allows for precise control of the microsphere diameter and the chemical composition. The microspheres can be used as calibrants or verification standards for explosives trace detection instruments. Gas chromatography/mass spectrometry analysis demonstrated that the composition of the microspheres was consistent with predicted concentrations based on the amount of analyte incorporated into the polymer solution and the inkjet operating parameters. We have demonstrated that the microspheres can be fabricated with a mass fraction of 70% of an analyte compound.     

A simple and convenient one-pot method for the preparation of heteroaryl-2-imidazoles from nitriles

A simple, convenient and high-yielding one-pot method for the synthesis of 2-heterocycle-substituted imidazoles from the corresponding nitriles has been developed. The procedure is easily scaleable and the workup does not involve chromatography. This synthesis is also applicable to the preparation of imidazoles with electron-poor aryl substituents.     

Observations on the use of microwave irradiation in azaheterocycle synthesis

A comparison of conventional heating and microwave irradiation in the synthesis of azaheterocycles is discussed. Microwave irradiation was found to increase the yields of the desired products, shorten the reaction times, and extended this chemistry to recalcitrant amide substrates and weak nucleophiles.