Discrete photopatternable pi-conjugated oligomers for electrochromic devices

Three discrete oligomeric systems including an all-thiophene ( T6) system, a thiophene/phenylene ( TPTTPT) system, and a thiophene/EDOT/phenylene ( TPEEPT) system have been constructed and characterized with emphasis on structural, optical, electrochemical, and spectroelectrochemical properties. For all three chromophores, the radical cation, the dication, and the pi-dimer have been identified and characterized. EPR spectroscopy reveals that the radical cations of TPTTPT and TPEEPT have g values of 2.008-2.012 and peak-to-peak widths in the range 4.2-5.3 G. Formation of the radical cation takes place at a lower potential for TPEEPT than for TPTTPT and T6, whereas subsequent oxidation to the dication occurs more easily for TPTTPT than for TPEEPT and T6. We ascribe this observation to more localized charges in the oxidized species of TPEEPT, which is supported by our finding that the radical cation of TPEEPT is less prone to undergo pi-dimerization than the radical cations of TPTTPT and T6. All the oxidized species are sufficiently stable to allow for optical characterization, and the relative positions of all absorption bands are found to be in agreement with the electrochemical data. For further solid-state modifications of these materials, we have effectively modified the synthetic design and grafted terminal functionalities (e.s. acrylates) onto the discrete oligomers. Of these novel materials, TPEEPT proves to be the most promising anodically coloring material for electrochromics, and it undergoes reversible switching between two different colored states (bright yellow and clear blue) and one almost transparent and color neutral state. Contrast ratios, measured as Delta% T at lambda max, are as high as 62.5%, and switching times are in the range 2-5 s for the coloration process, though significantly longer for the bleaching process. As a proof of concept, we have successfully constructed a simple photopatterned electrochromic device by exploiting the terminal acrylate functionalities of the oligomers in a UV-initiated cross-linking process. To the best of our knowledge, this is the first oligomer-based photopatterned electrochromic device reported in the literature.     

Therapeutic target metabolism observed using hyperpolarized 15N choline

Choline is a precursor of cellular phospholipid metabolism that provides Magnetic Resonance (MR) and Positron Emission Tomography (PET) biomarkers for cancer detection and response assessment. Employing Dynamic Nuclear Polarization we show that the MR signal of 15N in choline can be enhanced by at least 4 orders of magnitude with a relaxation time of ca. 4 min, providing a method to observe the action of choline kinase, an important target for novel cancer therapeutics.     

Rapid analysis of N-methylpyrrolidine in cefepime with thermal desorption ion mobility spectrometry

N-methyl-pyrrolidine (NMP) a potential impurity in the cephalosporin antibiotic cefepime is analysed using a rapid thermal desorption – ion mobility spectrometry (TD-IMS) method. The thermal desorption approach is shown to be capable of rapidly extracting NMP from the cefepime at 80 °C without causing thermal degradation of the cefepime. The ion mobility method has an analysis time of 1 min and demonstrates good linearity over a range from 0.3–3.0 μg ml^?1 of NMP, with limits of detection and quantification of 0.056 and 0.1875 μg ml^?1 respectively. The developed method was applied to the analysis of a cefepime sample and determined that NMP was present in a cefepime sample at a level of 0.0376 % with a percentage relative standard deviation (n = 6) of 3.2 %. This was compared with a LC-UV method which was in close agreement measuring NMP at 0.0384 % in the cefepime sample with a percentage RSD (n = 6) of 5.7 %. These results show that the TD-IMS method gives comparable data to the established LC methods and demonstrates the potential of TD-IMS for rapid measurement of volatile compounds in pharmaceutical matrices.     

Directed formation of micro- and nanoscale patterns of functional light-harvesting LH2 complexes

The precision placement of the desired protein components on a suitable substrate is an essential prelude to any hybrid "biochip" device, but a second and equally important condition must also be met: the retention of full biological activity. Here we demonstrate the selective binding of an optically active membrane protein, the light-harvesting LH2 complex from Rhodobacter sphaeroides, to patterned self-assembled monolayers at the micron scale and the fabrication of nanometer-scale patterns of these molecules using near-field photolithographic methods. In contrast to plasma proteins, which are reversibly adsorbed on many surfaces, the LH2 complex is readily patterned simply by spatial control of surface polarity. Near-field photolithography has yielded rows of light-harvesting complexes only 98 nm wide. Retention of the native optical properties of patterned LH2 molecules was demonstrated using in situ fluorescence emission spectroscopy.     

Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes

The first step of the reaction catalyzed by the homodimeric FabH from a dissociated fatty acid synthase is acyl transfer from acyl-CoA to an active site cysteine. We report that C1 to C10 alkyl-CoA disulfides irreversibly inhibit Escherichia coli FabH (ecFabH) and Mycobacterium tuberculosis FabH with relative efficiencies that reflect these enzymes' differential acyl-group specificity. Crystallographic and kinetic studies with MeSSCoA show rapid inhibition of one monomer of ecFabH through formation of a methyl disulfide conjugate with this cysteine. Reaction of the second subunit with either MeSSCoA or acetyl-CoA is much slower. In the presence of malonyl-ACP, the acylation rate of the second subunit is restored to that of the native ecFabH. These observations suggest a catalytic model in which a structurally disordered apo-ecFabH dimer orders on binding either the first substrate, acetyl-CoA, or the inhibitor MeSSCoA, and is restored to a disordered state on binding of malonyl-ACP.     

Forces between surfaces across nanoparticle solutions: role of size, shape, and concentration

Using a surface force apparatus, we have measured the normal forces between mica surfaces across various types of nanoparticles consisting of ZnS cores coated with a monolayer of physisorbed surfactant, dispersed in organic solvents. We focused on the effects of nanoparticle size, shape, and concentration on the force-distance profiles. Forces were exponentially repulsive when the surfactant layers were strongly bound to the nanoparticles and were roughly linear when there was adhesion between the nanoparticle cores, i.e., when the surfactant layers detached from the nanoparticles. In both cases, the range and magnitude of the forces were dependent upon the particle size, shape, and solution concentration. Fine details in the otherwise smooth force-distance profiles indicate specific effects due to particle chemistry and geometry and the existence of first-order disorder-order phase transitions upon confinement. Small amounts of water in the (hydrophobic) organic solvents had dramatic effects on the measured forces. Understanding and controlling the effects of particle shape, size, and concentration and the presence of water (or other surface-active solutes) on particle-particle and particle-surface interactions are important for the processing of nanoparticles into ordered superstructured materials.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.