Microchannel systems in titanium and silicon for structural and mechanical studies of aligned protein self-assemblies

We report a technique for the alignment of self-assembled protein systems, such as F-actin bundles and microtubules, in a surface-modified titanium or silicon microfluidic device. Assembling filamentous protein systems in a confined geometry produces highly aligned samples for structural and mechanical studies. Biomolecular self-assembly can be investigated in a controlled fashion under different molecular concentration gradients and conditions along a channel length. We have shown that surface-modified devices produced via a high aspect ratio etch process in titanium and silicon can be used to confine and control such macromolecular assemblies and present examples of F-actin bundles and microtubules in this system.     

Quantitative structure-activity relationships by neural networks and inductive logic programming. II. The inhibition of dihydrofolate reductase by triazines

Summary One of the largest available data sets for developing a quantitative structure-activity relationship (QSAR) — the inhibition of dihydrofolate reductase (DHFR) by 2,4-diamino-6,6-dimethyl-5-phenyl-dihydrotriazine derivatives — has been used for a sixfold cross-validation trial of neural networks, inductive logic programming (ILP) and linear regression. No statistically significant difference was found between the predictive capabilities of the methods. However, the representation of molecules by attributes, which is integral to the ILP approach, provides understandable rules about drug-receptor interactions.     

Solvent effects on supramolecular gel-phase materials: two-component dendritic gel

The self-assembly of diaminododecane with dendritic l-lysine-based peptides to form gel-phase materials was investigated in a range of different solvents. The degree of structuring was modulated by the solvent employed, an effect which induced subtle changes in the mesoscale aggregate morphology and macroscopic behavior of the self-assembled state. In this paper a range of different solvent parameters are investigated, and it is clearly shown that macroscopic gelation can be related to a solvent polar solubility parameter for this system. The results also show a dependence on Kamlet-Taft hydrogen bonding parameters, and this clearly demonstrates the role of the solvent environment in terms of dendron--dendron intermolecular hydrogen bonding and its impact on the supramolecular chiral organization of the assembled superstructure.     

An organocatalytic oxidative coupling strategy for the direct synthesis of arylated quaternary stereogenic centers

A broadly applicable oxidative coupling strategy of 3-substituted catechols and carbon-centered pro-nucleophiles for the construction of arylated quaternary stereogenic centers has been developed. Pivoting on a base-catalyzed addition of a carbon-centered acid to an in situ generated o-benzoquinone, the method is general and atom-economical and provides remarkably efficient access to one of the most challenging structural motifs. Furthermore, use of chiral bifunctional organocatalysts allows the process to be rendered asymmetric (up to 81% ee).     

Modular construction of oxide structures--compositional control of transition metal coordination environments

The effects of reaction temperature and pO2 were investigated on a series of (Ba,Ca,Nd)FeO3-delta perovskite systems in order to isolate phases containing ordered arrangements of the distinct vacancy and cation ordering patterns identified in less compositionally complex iron oxide systems. Initial synthesis in air at high temperature yields cubic perovskite phases (I) with average iron oxidation states higher than 3; selected area electron diffraction together with diffuse features observed in the synchrotron X-ray diffraction (SXRD) patterns of these materials show evidence of small domains of short-range cation and vacancy order. Annealing these materials in nitrogen or in a sealed tube in the presence of an NiO/Ni buffer yielded the Fe(3+) phase Ca2Ba2Nd2Fe6O16 (II), closely related to Sr2LaFe3O8 but with partial cation order as well as anion order present the larger Ba cations are largely present in the 12-coordinate site between the octahedral iron layers, and Ca is largely present in 10-coordinate sites between octahedral and tetrahedral sites. Further reduction of Ca2Ba2Nd2Fe6O16 using a Zr getter yields the mixed-valence phase Ca2Ba2Nd2Fe6O15.6 (III). The structure of III was solved by maximum entropy analysis of XRD data coupled with analysis of high-temperature neutron diffraction data and refined against combined SXRD and high-Q ambient-temperature neutron data. This material crystallizes in a 20-fold perovskite super cell (Imma, a approximately square root(2 x a(p), b approximately 10 x a(p), c approximately square root(x 2a(p)) and can be visualized as an intergrowth between brownmillerite (Ca2Fe2O5) and the YBa2Fe3O8 structure. There are three distinct iron coordination environments, octahedral (O), square-pyramidal (Sp), and trigonal planar (Tp, formed by distorting the tetrahedral site in brownmillerite), which form a Sp-O-Tp-O-Sp repeat. Bond valence calculations indicate that Tp is an Fe(2+) site, while the O and Sp sites are Fe(3+). The A-site cations are also partially ordered over three distinct sites: 8-coordinate between the Sp layers, 10-coordinate between Tp and O layers, and 12-coordinate between Sp and O layers. Mossbauer spectroscopy, magnetometry, and variable-temperature neutron diffraction show that the material undergoes two magnetic transitions at approximately 700 and 255 K.     

Lipid bilayer discs and banded tubules: photoinduced lipid sorting in ternary mixtures

The self-assembly of biological amphiphiles has proved a fascinating topic in recent years, the hollow cylindrical lipid tubule morphology being of particular interest due to its potential applications in "soft" microtechnologies. Lateral coexistence of liquid-ordered (lo) and liquid-disordered (ld) phases, which may resemble raft formation in cell membranes, was investigated in lipid tubules, prepared from 1,2-dioleoyl-sn-glycero-3-phosphocholine, egg-sphingomyelin, and cholesterol. Fluorescence microscopy shows that the appearance of micrometer-scale lo domains in the lipid tubule is not an intrinsic phase behavior of the system but a consequence of photoinduced lipid peroxidation. Most interestingly, new photoinduced bilayer structures: lipid discs, essentially stable flattened liposomes, were observed for the first time in a model membrane system. This investigation not only aids in our understanding of lipid sorting phenomena in cell membranes but also demonstrates how control of this process may provide a route to the generation of new, functional structures.     

Developing the Saegusa–Ito Cyclisation for the Synthesis of Difluorinated Cyclohexenones

Palladium(II)‐catalysed cycloalkenylation (Saegusa–Ito cyclisation) has been used for the first time to transform difluorinated silylenol ethers to difluorinated cycloalkenones under mild conditions. The silylenol ether precursors were prepared in two high‐yielding steps from trifluoroethanol, and cyclised in moderate to good yields. A combination of air and copper(I) chloride in acetonitrile gave the turnover of the initial palladium(II) salt, whereas the provision of an oxygen atmosphere ensured more rapid reaction. Annulations required a minimum level of substitution on the chain, but failed when the alkene was substituted. Annelations allowed a range of n,6‐bicyclic systems to be prepared and afforded three products, in which heterocycles were fused to the new cyclohexenone. The least substituted system explored underwent cyclisation followed by terminal oxidation to a cyclic enal, which corresponded to a Wacker product of unusual regiochemistry.     

Keeping the spotlight on quality from a distance

 Maintaining the quality of testing in remote locations can be demanding of laboratory resources in terms of daily visits to instruments and providing support outside of normal working hours. Recently technology and software solutions have appeared to reduce this burden for laboratory scientists dramatically. The AVL Auto QC unit, in conjunction with OMNILink software, allow laboratory staff to perform many quality control and maintenance procedures on instruments in wards and medical units from a PC in the central laboratory. Assessment of this technology and software in the Special Baby Care Unit at Bradford Royal Infirmary has demonstrated many benefits including reduction in ward visits, better support out of hours, regular quality control checks, and improved analytical quality. Received: 15 April 2000 · Accepted: 15 April 2000