Freezing the Dynamic Gap for Selectivity: Motion‐Based Design of Inhibitors of the Shikimate Kinase Enzyme

Shikimate kinase (SK), the fifth enzyme of the aromatic amino acid biosynthesis, is a recognized target for antibiotic drug discovery. The potential of the distinct dynamic apolar gap, which isolates the natural substrate from the solvent environment for catalysis, and the motion of Mycobacterium tuberculosis and Helicobacter pylori SK enzymes, which was observed by molecular dynamics simulations, was explored for inhibition selectivity. The results of the biochemical and computational studies reveal that the incorporation of bulky groups at position C5 of 5‐aminoshikimic acid and the natural substrate enhances the selectivity for the H. pylori enzyme due to key motion differences in the shikimic acid binding domain (mainly helix α5). These studies show that the less‐exploited motion‐based design approach not only is an alternative strategy for the development of competitive inhibitors, but could also be a way to achieve selectivity against a particular enzyme among its homologues.     

Miscible blends of poly(ethylene oxide) with brush copolymers of poly(vinyl alcohol)‐graft‐poly(l‐lactide)

Even though poly(ethylene oxide) (PEO) is immiscible with both poly(l ‐lactide) (PLLA) and poly(vinyl alcohol) (PVA), this article shows a working route to obtain miscible blends based on these polymers. The miscibility of these polymers has been analyzed using the solubility parameter approach to choose the proper ratios of the constituents of the blend. Then, PVA has been grafted with l ‐lactide (LLA) through ring‐opening polymerization to obtain a poly(vinyl alcohol)‐graft‐poly(l ‐lactide) (PVA‐g‐PLLA) brush copolymer with 82 mol % LLA according to ¹H and ¹³C NMR spectroscopies. PEO has been blended with the PVA‐g‐PLLA brush copolymer and the miscibility of the system has been analyzed by DSC, FTIR, OM, and SEM. The particular architecture of the blends results in DSC traces lacking clearly distinguishable glass transitions that have been explained considering self‐concentration effects (Lodge and McLeish) and the associated concentration fluctuations. Fortunately, the FTIR analysis is conclusive regarding the miscibility and the specific interactions in these systems. Melting point depression analysis suggests that interactions of intermediate strength and PLOM and SEM reveal homogeneous morphologies for the PEO/PVA‐g‐PLLA blends. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 1217–1226     

Weighted Shift Operators Which are m-Isometries

We give a characterization of m-isometric operators on a separable Hilbert space. Moreover, we characterize the unilateral weighted shift operators which are m-isometries.     

Nonstoichiometric spinel ferrites obtained from alpha-NaFeO2 via molten media reactions

Different solid/liquid "exchange" reactions involving divalent cations, protons, or ammonium ions have been performed at low/moderate temperatures (between 80 and 500 degrees C) on alpha-NaFeO2 dipped in molten salts (or acid) media. Several ferrites have been obtained which are nonstoichiometric with partially inverse spinel structures. When sodium is replaced by divalent cations (Mg2+, Co2+, Ni2+, and Zn2+), the obtained ferrites are hyperstoichiometric (cation/oxygen ratio higher than 3/4) whereas proton or ammonium reactions result in hypostoichiometric materials (cation/oxygen lower than 3/4). All these ferrites present a platelet-like morphology and show ferrimagnetic, soft magnet behavior.     

Photoelectrochemical study of Zn cytochrome-c immobilised on a nanoporous metal oxide electrode

Transient optical spectroscopies and photocurrent action spectra are used to demonstrate photoinduced charge separation between zinc-substituted cytochrome c and a nanocrystalline TiO2 electrode.     

Stereochemical memory in the temperature-dependent photodenitrogenation of bridgehead-substituted DBH-type azoalkanes: inhibition of inverted-housane formation in the diazenyl diradical through the mass effect (inertia) and steric hindrance

The photochemical denitrogenation of the cyclopentene-annelated DBH-type azoalkanes 1 has been examined in solution as a function of bridgehead substitution and temperature. For all derivatives, namely, the unsubstituted 1a(H/H), monomethyl 1b(Me/H) dimethyl 1c(Me/Me), monophenyl 1d(Ph/H), and diphenyl 1e(Ph/Ph), the temperature-dependent ratio of syn and anti housanes 2 provides experimental support for a competition between the singlet (high temperature) and triplet (low temperature) reaction channels in the direct photolysis. The syn/anti ratio of the housanes 2 depends on the extent and type of bridgehead substitution; the amount of the anti diastereomer (retention) follows the order Ph > Me > H, and double substitution is more effective than single. This stereochemical memory is interpreted in terms of the mass effect (inertia) of the substituents and steric interaction (size) between the substituents at the bridgehead and the methylene bridge during the deazetation step of the transient diazenyl diradical conformations (1)DZ (exo-ax) and (1)DZ (exo-eq). These conformers are impulsively generated upon decay of the (1)(n,pi)-excited azoalkane, a trajectory assessed through computational work. The new mechanistic feature disclosed by the unprecedented anti stereoselectivity (retention) is the intervention of a puckered 1,3-cyclopentanediyl singlet diradical (1)DR as product bifurcation step, whose conformational relaxation to the planar species (loss of stereochemical memory) is encumbered by bridgehead substitution.     

Laguerre geometry of surfaces with plane lines of curvature

We study surfaces with plane lines of curvature in the framework of Laguerre geometry and provide explicit representation formulae for these surfaces in terms of a potential function. As an application, we explicitly integrate allL- minimal surfaces with plane curvature lines. Partially supported by MURST 40.     

A representation formula of sum rules for zeros of polynomials

A representation formula in terms of Lucas polynomials of the second kind in several variables (see formula (4.3)), for the sum rulesJ _s ⁽ⁱ⁾ introduced by K.M. Case [1] and studied by J.S. Dehesa et al. [2]–[3] in order to obtain informations about the zeros’ distribution of eigenfunctions of a class of ordinary polynomial differential operator, is derived. Lavoro eseguito nell’ambito del G.N.I.M. del C.N.R.     

From the Galilei to the Lorentz group in a general light-cone frame

The most general coordinate system in which the Galilean symmetries of the ordinary and the Bell and Ruegg light-cone frames appear is found. With a modification of this general coordinate system it is possible to go from the Galilei group in two space dimensions to the Lorentz group, a process inverse to the contraction of the Lorentz group with respect to the subgroup of rotations. As an example of the applicability of this modified general light-cone frame, the two-dimensional Schrödinger-Pauli equation is obtained to all orders.