Homogeneous photochemical oxidation via singlet O2 in supercritical CO2

This communication describes the reaction chemistry of singlet oxygen in supercritical carbon dioxide, demonstrating rapid and quantitative conversion of alpha-terpinene to ascaridole.     

How large does a compound screening collection need to be?

Increasingly, chemical libraries are being produced which are focused on a biological target or group of related targets, rather than simply being constructed in a combinatorial fashion. A screening collection compiled from such libraries will contain multiple analogues of a number of discrete series of compounds. The question arises as to how many analogues are necessary to represent each series in order to ensure that an active series will be identified. Based on a simple probabilistic argument and supported by in-house screening data, guidelines are given for the number of compounds necessary to achieve a "hit", or series of hits, at various levels of certainty. Obtaining more than one hit from the same series is useful since this gives early acquisition of SAR (structure-activity relationship) and confirms a hit is not a singleton. We show that screening collections composed of only small numbers of analogues of each series are sub-optimal for SAR acquisition. Based on these studies, we recommend a minimum series size of about 200 compounds. This gives a high probability of confirmatory SAR (i.e. at least two hits from the same series). More substantial early SAR (at least 5 hits from the same series) can be gained by using series of about 650 compounds each. With this level of information being generated, more accurate assessment of the likely success of the series in hit-to-lead and later stage development becomes possible.     

Simultaneous determination of bisphenol A, triclosan, and tetrabromobisphenol A in human serum using solid-phase extraction and gas chromatography-electron capture negative-ionization mass spectrometry

This study aimed at optimizing and validating a sensitive method for simultaneous determination of bisphenol A (BPA), triclosan (TCS), and tetrabromobisphenol A (TBBPA) in human serum using solid-phase extraction (SPE) and gas chromatography coupled to electron-capture negative-ionization mass spectrometry (GC-ECNI/MS). Sample preparation involved denaturation of serum proteins with formic acid followed by SPE on an Oasis HLB cartridge. Fractionation was performed on Florisil from which the phenolic compounds were eluted with methanol-dichloromethane (DCM) (5:1, v/v). The phenolic fraction was further derivatized with pentafluoropropionic acid anhydride (30 min at 70 degrees C). Further liquid-liquid partitioning using hexane-DCM (4:1, v/v) and K(2)CO(3) 3% aqueous solution was used to eliminate excess reagent and acidic by-products formed during derivatization. The cleaned extract was injected into a GC-ECNI/MS system operated in selected ion monitoring mode. For thorough method validation, each step of the procedure was rigorously optimized. The method limits of quantitation for BPA, TCS, and TBBPA were 0.28 ng mL(-1), 0.09 ng mL(-1) and 0.05 ng mL(-1), respectively. Furthermore, the method was applied to 21 Belgian human serum samples. The median concentrations obtained for BPA (0.71 ng mL(-1)) and TCS (0.52 ng mL(-1)) in Belgian human serum samples were similar to previously reported data for human fluids. Slightly higher levels of TBBPA (0.08 ng mL(-1)) were found in Belgium samples compared to Norwegian serum.     

Relaxation in Reactive Flows

We consider convective systems in a bounded domain, in which viscous fluids described by the Stokes system are coupled using the Boussinesq approximation to a reaction-advection-diffusion equation for the temperature. We show that the resulting flows possess relaxation-enhancing properties in the sense of [CoKRZ]. In particular, we show that solutions of the nonlinear problems become small when gravity is sufficiently strong due to the improved interaction with the cold boundary. As an application, we deduce that the explosion threshold for power-like nonlinearities tends to infinity in the large Rayleigh number limit. We also discuss the behavior of the principal eigenvalues of the corresponding advection-diffusion problem and the quenching phenomenon for reaction-diffusion equations. Received: March 2007, Revision: May 2007, Accepted: May 2007     

Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

Background  

To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala) and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm) with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme.     

A unique six-membered chelated iridium complex

The reaction of 2-(3-methylbiphenyl-2-yl)pyridine with IrCl(3).nH(2)O in the presence of water incorporates a tightly bonded CO at the iridium center; in the subsequent reaction with picolinic acid a complex revealing an unusual CH activation of a methyl group is formed.     

One-pot synthesis of functionalized piperid-4-ones: a four-component condensation

The one-pot synthesis of highly substituted piperid-4-ones has been achieved. Diketene is added to a tosyl imine in the presence of TiCl(4) and MeOH, followed by 1 equiv of aldehyde to generate 2,6-disubstituted nonsymmetrical piperid-4-ones as a mixture of cis-/trans-diastereomers in good yields. This mixture of diastereomers can be converted to a single 2,6- cis-diastereomer by epimerization with K(2)CO(3).     

Molecular Lanthanide Switches for Magnetism and Photoluminescence

Solvation of [(CNT)Ln(η⁸-COT)] (Ln=La, Ce, Nd, Tb, Er; CNT=cyclononatetraenyl, i.e., C₉H₉⁻; COT=cyclooctatetraendiid, i.e., C₈H₈²⁻) complexes with tetrahydrofuran (THF) gives rise to neutral [(η⁴-CNT)Ln(thf)₂(η⁸-COT)] (Ln=La, Ce) and ionic [Ln(thf)_x(η⁸-COT)][CNT] (x=4 (Ce, Nd, Tb), 3 (Er)) species in a solid-to-solid transformation. Due to the severe distortion of the ligand sphere upon solvation, these species act as switchable luminophores and single-molecule magnets. The desolvation of the coordinated solvents can be triggered by applying a dynamic vacuum, as well as a temperature gradient stimulus. Raman spectroscopic investigations revealed fast and fully reversible solvation and desolvation processes. Moreover, we also show that a Nd:YAG laser can induce the necessary temperature gradient for a self-sufficient switching process of the Ce(III) analogue in a spatially resolved manner.