Structural comparison of endomorphin-2 and its conformationally restricted analog

In the present study, the effect of a conformational constraint introduced into the endomorphin-2 (Tyr-Pro-Phe-Phe-NH₂, EM-2) structure was studied using computational analysis and radioligand binding assay. EM-2 was modified by connecting nitrogen atoms of both phenylalanine residues by a methylene bridge. The obtained analog did not bind to the μ- or δ-opioid receptors in the in vitro studies. The computational analysis of this analog showed twisted, type IV turns and the absence of canonical β-turns typical for the EM-2 structure, which can be explained by the lack of hydrogen bonds involving Phe⁴. Our results show that the introduction of chemical constraint in the EM-2 structure has a significant effect on opioid receptor affinity and in vitro bioactivity.     

A space-indexed formulation of packing boxes into a larger box

Current integer programming solvers fail to decide whether 12 unit cubes can be packed into a 1×1×11 box within an hour using the natural relaxation of Chen/Padberg. We present an alternative relaxation of the problem of packing boxes into a larger box, which makes it possible to solve much larger instances.     

Aerodynamic mass spectrometry interfacing of microdevices without electrospray tips

A new concept for electrospray coupling of microfluidic devices with mass spectrometry was developed. The sampling orifice of the time-of-flight mass spectrometer was modified with an external adapter assisting in formation and transport of the electrosprayed plume from the multichannel polycarbonate microdevice. The compact disk sized microdevice was designed with radial channels extending to the circumference of the disk. The electrospray exit ports were formed by the channel openings on the surface of the disk rim. No additional tips at the channel exits were used. Electrospray was initiated directly from the channel openings by applying high voltage between sample wells and the entrance of the external adapter. The formation of the spatially unstable droplet at the electrospray openings was eliminated by air suction provided by a pump connected to the external adapter. Compared with the air intake through the original mass spectrometer sampling orifice, more than an order of magnitude higher flow rate was achieved for efficient transport of the electrospray plume into the mass spectrometer. Additional experiments with electric potentials applied between the entrance sections of the external adapter and the mass spectrometer indicated that the air flow was the dominant transport mechanism. Basic properties of the system were tested using mathematical modeling and characterized using ESI/TOF-MS measurements of peptide and protein samples.     

Reactivity of cyclic sulfamidates towards sulfur-stabilised enolates. Stereocontrolled synthesis of functionalised lactams

A structurally representative series of 1,2- and 1,3-cyclic sulfamidates react with enolates derived from methyl alpha-phenylthioacetate 9b to give 5- and 6-substituted alpha-phenylthio lactams 20-24. These products provide, via the corresponding sulfoxides, an entry to alpha,beta-unsaturated lactams e.g. 12, 27, 29 and their alpha-phenylthio analogues e.g. 26 and 30. With the enantiomerically pure 1,2-cyclic sulfamidates 10, 15 and 17, these reactions all proceed with no detectable loss of stereochemical integrity.     

Relaxometric and solution NMR structural studies on ditopic lanthanide(III) complexes of a phosphinate analogue of DOTA with a fast rate of water exchange

A novel "ditopic" ligand containing two monophosphinate triacetate DOTA-like units linked by a thiourea bridge has been synthesized and its complexes with Ln3+ ions (Ln = Y, Eu, Gd, Dy) investigated by NMR spectroscopy and relaxometry. The presence of one water molecule in the first coordination sphere has been determined by the measurement of the dysprosium(III)-induced 17O NMR shifts. The 1H and 31P NMR spectra of the Eu(III) derivative indicate a higher abundance of the fast-exchanging twisted square antiprismatic (m) isomer than the isomeric square antiprismatic (M; m/M = 3:2) complex. The analysis of the 89Y and 13C T1 NMR relaxation times in the Gd(III)/Y(III) mixed complex have provided useful structural information. Values of ca. 6.3 and 8.2 A for the Gd...Y and Gd...C distances, respectively, have been estimated which indicate a rather compact solution structure. This result finds support in the value of the relaxivity whose increase (at 20 MHz and 298 K) on passing from the monomeric (5.7 s(-1) mM(-1)) to the ditopic complex (8.2 s(-1) mM(-1)) can be attributed to the doubling of the inner-sphere term following the doubling of the molecular size. The structural and dynamic relaxivity-controlling parameters were assessed by a simultaneous fitting of the variable temperature 17O NMR and 1H NMRD relaxometric data. The mean water residence lifetime (298tauM) has been found to be 53 ns, one of the shortest values reported for ditopic complexes. The reorientational correlation time is two times longer (298tauR = 183 ps) than the corresponding value of the parent monomeric Gd(III) complex, thus supporting the view of a limited degree of internal rotation. The possible influence of magnetic Gd-Gd coupling has been excluded by a comparison of the 1H NMRD profiles of the homodinuclear Gd(III)/Gd(III) and the heterodinuclear Gd(III)/Y(III) complexes.     

Ideal convergence of continuous functions

For a given ideal I⊆P(ω), IC(I) denotes the class of separable metric spaces X such that whenever is a sequence of continuous functions convergent to zero with respect to the ideal I then there exists a set of integers {m₀<m₁<?} from the dual filter F(I) such that limi→∞fmi(x)=0 for all x∈X. We prove that for the most interesting ideals I, IC(I) contains only singular spaces. For example, if I=Id is the asymptotic density zero ideal, all IC(Id) spaces are perfectly meager while if I=Ib is the bounded ideal then IC(Ib) spaces are σ-sets.     

Conformational behavior of simple furanosides studied by optical rotation

Experimental and theoretical specific optical rotations (OR) of anhydro, epithio, and epiminoderivatives of methyl tetrofuranosides in chloroform solutions have been compared and used as a tool for exploring their conformational behavior. The potential energy surfaces of these saccharides with reduced flexibility were examined with the density functional theory and the MP2 and CCSD(T) wavefunctions methods. Theoretical ORs were obtained by Boltzmann averaging of values calculated for local minima. Resultant rotations could be used to assess the quality of the DFT and MP2 relative conformer energies. OR values calculated for equilibrium geometries in vacuum were significantly improved when the solvent was accounted for by a polarizable continuum model and first and diagonal second OR derivatives were used for an anharmonic vibrational averaging. The DFT used as a default method reproduced the experimental data fairly well. A modified B3LYP functional containing 70% of HF exchange further improved the results. Because of the strong dependence of OR on the conformation, not only the absolute configuration could be determined, but also the conformational populations were estimated. Likewise, the predicted dependence of OR on the light wavelength well agreed with experiment. The increasing precision of the contemporary computational methods thus makes it possible to relate the specific rotation to more detailed features in molecular structure. © 2010 Wiley Periodicals, Inc. J Comput Chem 2010     

On 2-walks in chordal planar graphs

A 2-walk is a closed spanning trail which uses every vertex at most twice. A graph is said to be chordal if each cycle different from a 3-cycle has a chord. We prove that every chordal planar graph G with toughness has a 2-walk.     

Oxygen evolution on Ru1 − x Ni x O2 − y nanocrystalline electrodes

Nanocrystalline Ru_1 − x Ni _x O_2 − y with 0.02 < x < 0.30 were prepared by a sol–gel approach at temperatures between 300 and 600 °C. XRD patterns of the prepared materials indicate a single-phase character conforming to a tetragonal syngony. All prepared materials are sufficiently stable in acid media and show activity towards oxygen evolution. The activity towards oxygen evolution reaction of the materials with constant chemical composition decreases with increasing particle size. The increasing Ni content enhances the electrocatalytic activity in a stepwise manner with abrupt changes for materials containing approximately 5% or 15% of the cationic sites substituted by Ni.