E-1,2-Dichlorovinyl ethers as irreversible protease inhibitors

The synthesis of a novel motif for threonine protease inhibition is described. The desired E-1,2-dichlorovinyl ethers are obtained from alcohols and trichloroethylene as single diastereomers. Aqueous treatment at pH 11 unmasks the hidden α-chloroacetate, which is required for the reaction with the active site of the protease.     

Approaching the Integer‐Charge Transfer Regime in Molecularly Doped Oligothiophenes by Efficient Decarboxylative Cross‐Coupling

A library of symmetrical linear oligothiophene was prepared employing decarboxylative cross‐coupling reaction as the key transformation. Thiophene potassium carboxylate salts were used as cross‐coupling partners without the need of co‐catalyst, base, or additives. This method demonstrates complete chemoselectivity and is a comprehensive greener approach compared to the existing methods. The modularity of this approach is demonstrated with the preparation of discreet oligothiophenes with up to 10 thiophene repeat units. Symmetrical oligothiophenes are prototypical organic semiconductors where their molecular electrical doping as a function of the chain length can be assessed spectroscopically. An oligothiophene critical length for integer charge transfer was observed to be 10 thiophene units, highlighting the potential use of discrete oligothiophenes as doped conduction or injection layers in organic electronics applications.     

Electron holography with a Cs-corrected transmission electron microscope.

Cs correctors have revolutionized transmission electron microscopy (TEM) in that they substantially improve point resolution and information limit. The object information is found sharply localized within 0.1 nm, and the intensity image can therefore be interpreted reliably on an atomic scale. However, for a conventional intensity image, the object exit wave can still not be detected completely in that the phase, and hence indispensable object information is missing. Therefore, for example, atomic electric-field distributions or magnetic domain structures cannot be accessed. Off-axis electron holography offers unique possibilities to recover completely the aberration-corrected object wave with uncorrected microscopes and hence we would not need a Cs-corrected microscope for improved lateral resolution. However, the performance of holography is affected by aberrations of the recording TEM in that the signal/noise properties ("phase detection limit") of the reconstructed wave are degraded. Therefore, we have realized off-axis electron holography with a Cs-corrected TEM. The phase detection limit improves by a factor of four. A further advantage is the possibility of fine-tuning the residual aberrations by a posteriori correction. Therefore, a combination of both methods, that is, Cs correction and off-axis electron holography, opens new perspectives for complete TEM analysis on an atomic scale.     

Redox-active p-quinone-based Bis(pyrazol-1-yl)methane ligands: synthesis and coordination behaviour

The synthesis, structural characterisation and coordination behaviour of mono- and ditopic p-hydroquinone-based bis(pyrazol-1-yl)methane ligands is described (i.e., 2-(pz2CH)C6H3(OH)2 (2a), 2-(pz2CH)-6-(tBu)C6H2(OH)2 (2b), 2-(pz2CH)-6-(tBu)C6H2(OSiiPr3)(OH) (2c), 2,5-(pz2CH)2C6H2(OH)2 (4)). Ligands 2a, 2b and 4 can be oxidised to their p-benzoquinone state on a preparative scale (2a ox, 2b ox, 4 ox). An octahedral Ni II complex [trans-Ni(2c)2] and square-planar Pd II complexes [Pd2bCl2] and [Pd2b ox Cl2] have been prepared. In the two Pd II species, the ligands are coordinated only through their pyrazolyl rings. The fact that [Pd2bC12] and [Pd2b oxC12] are isolable compounds proves that redox transitions involving the p-quinone substituent are fully reversible. In [Pd2b oxCl2], the methine proton is highly acidic and can be abstracted with bases as weak as NEt(3). The resulting anion dimerises to give a dinuclear macrocyclic Pd II complex, which has been structurally characterised. The methylated ligand 2-(pz2CMe)C6H3O2 (11 ox) and its Pd II complex [Pd11 oxCl2] are base-stable. A new class of redox-active ligands is now available with the potential for applications both in catalysis and in materials science.     

Live Monitoring of Strain-Promoted Azide Alkyne Cycloadditions in Complex Reaction Environments by Inline ATR-IR Spectroscopy

The strain-promoted azide alkyne cycloaddition (SPAAC) is a powerful tool for forming covalent bonds between molecules even under physiological conditions, and therefore found broad application in fields ranging from biological chemistry and biomedical research to materials sciences. For many applications, knowledge about reaction kinetics of these ligations is of utmost importance. Kinetics are commonly assessed and studied by NMR measurements. However, these experiments are limited in terms of temperature and restricted to deuterated solvents. By using an inline ATR-IR probe we show that the cycloaddition of azides and alkynes can be monitored in aqueous and even complex biological fluids enabling the investigation of reaction kinetics in various solvents and even human blood plasma under controlled conditions in low reaction volumes.     

Approaching the Integer-Charge Transfer Regime in Molecularly Doped Oligothiophenes by Efficient Decarboxylative Cross-Coupling

A library of symmetrical linear oligothiophene was prepared employing decarboxylative cross-coupling reaction as the key transformation. Thiophene potassium carboxylate salts were used as cross-coupling partners without the need of co-catalyst, base, or additives. This method demonstrates complete chemoselectivity and is a comprehensive greener approach compared to the existing methods. The modularity of this approach is demonstrated with the preparation of discreet oligothiophenes with up to 10 thiophene repeat units. Symmetrical oligothiophenes are prototypical organic semiconductors where their molecular electrical doping as a function of the chain length can be assessed spectroscopically. An oligothiophene critical length for integer charge transfer was observed to be 10 thiophene units, highlighting the potential use of discrete oligothiophenes as doped conduction or injection layers in organic electronics applications.     

Parallel implementation of γ‐point pseudopotential plane‐wave DFT with exact exchange

Semi‐local functionals commonly used in density functional theory (DFT) studies of solids usually fail to reproduce localized states such as trapped holes, polarons, excitons, and solitons. This failure is ascribed to self‐interaction which creates a Coulomb barrier to localization. Pragmatic approaches in which the exchange correlation functionals are augmented with small amount of exact exchange (hybrid‐DFT, e.g., B3LYP and PBE0) have shown to promise in rectifying this type of failure, as well as producing more accurate band gaps and reaction barriers. The evaluation of exact exchange is challenging for large, solid state systems with periodic boundary conditions, especially when plane‐wave basis sets are used. We have developed parallel algorithms for implementing exact exchange into pseudopotential plane‐wave DFT program and we have implemented them in the NWChem program package. The technique developed can readily be employed in Γ‐point plane‐wave DFT programs. Furthermore, atomic forces and stresses are straightforward to implement, making it applicable to both confined and extended systems, as well as to Car‐Parrinello ab initio molecular dynamic simulations. This method has been applied to several systems for which conventional DFT methods do not work well, including calculations for band gaps in oxides and the electronic structure of a charge trapped state in the Fe(II) containing mica, annite. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010