Natural and Synthetic Xanthones as Monoamine Oxidase Inhibitors: Biological Assay and 3D‐QSAR

Fifty‐nine xanthones (=9H‐xanthen‐9‐ones) of natural or synthetic origin were investigated for their inhibitory activity toward monoamine‐oxidase A (MAO‐A) and MAO‐B. The compounds demonstrated reversible, time‐independent activities, with selectivity toward MAO‐A. The most active inhibitor had an IC₅₀ of 40 nM . Electron absorption spectroscopy revealed the formation of a 1 : 1 charge‐transfer complex between lumiflavine and xanthones. 3D‐QSAR Studies according to the CoMFA/GOLPE procedure provided information on the relationship between steric and electrostatic fields and MAO‐A inhibition. The ALMOND procedure yielded additional topographical information on structural factors favoring activity.     

Novel Basic Isoflavones as Inhibitors of Bone Resorption

A number of aminoalkoxy analogues of ipriflavone (=7‐(1‐methylethoxy)isoflavone) were prepared and examined for their capacity to inhibit bone resorption induced by bovine parathyroid hormone fragment 1 – 34. Good‐to‐high activities were found for 7‐(aminoalkoxy)isoflavone analogues. Their activity was influenced by a number of structural features, among which the length of the basic side chain, the basicity of the amino group, and the nature and position of substituents on the 3‐phenyl ring. 4′‐(Aminoalkoxy)ipriflavone derivatives were less active.     

Kristallstruktur,Phasenumwandlung und Kaliumionenleitfähigkeit von Kaliumtrifluormethylsulfonat

Crystal Structure, Phase Transition, and Potassium Ion Conductivity of Potassium Trifluoromethanesulfonate According to the results of temperature dependent powder diffractometry (Guinier‐Simon‐technique) potassium trifluoromethanesulfonate is dimorphic. The phase transition occurs between –63 °C and –45 °C. The low‐temperature modification crystallizes monoclinic with a = 10.300(3) Å, b = 6.052(1) Å, c = 14.710(4) Å, β = 111.83(2)° (–120 °C) and the room‐temperature modification with a = 10.679(5) Å, b = 5.963(2) Å, c = 14.624(5) Å, β = 111.57(3)°, Z = 6, P2₁. According to single crystal structure determination, potassium trifluoromethanesulfonate consists of three different potassium‐oxygen‐coordination polyhedra, linked by sulfur atoms of the trifluoromethanesulfonate groups. This results in a channel structure with all lipophilic trifluoromethane groups pointing into these channels. By means of DSC, the transition temperature and enthalpy have been determined to be –33 °C and 0.93 ± 0.03 kJ/mol, respectively. The enthalpy of melting (237 °C) for potassium trifluoromethanesulfonate is 13.59 kJ/mol, the potassium ionic conductivity is 3.68 · 10^–6 Scm^–1 at 205 °C.     

Limit analysis of masonry vaults by means of curved shell finite elements and homogenization

The study of masonry vaults should take into account the essentials of the material “masonry” – i.e. heterogeneity, almost no resistance to tension combined with a good compressive strength and a high friction coefficient, as well as the overall importance of the geometry for achieving the equilibrium.In this paper, a new six-noded triangular curved element, specifically developed for the kinematic limit analysis of masonry shells, is presented. Plastic dissipation is allowed only at the interfaces (generalized cylindrical hinges) between adjoining elements for combined membrane actions, bending moment, torsion and out-of-plane shear, as it is required for the analysis of thick (Reissner–Mindlin) shells. An upper bound of the collapse load is so obtained, since, looking at the dual formulation, the admissibility of the stress state is imposed only at the element boundaries. Masonry strength domain at each interface between contiguous triangular elements is evaluated resorting to a suitable upper bound FE homogenization procedure. The model is assessed through several numerical simulations on a number of masonry shells experimentally tested until collapse. In particular, the dependence of the collapse multiplier on the mesh and on the material parameters (sensitivity analysis) is thoroughly discussed.     

Preliminary study on application PE filler modified by radiation

Mineral filler magnesium oxide (MgO) has been modified by a grafting process initiated by electron beam treatment. The methacrylic acid (MAA), methyl methacrylate (MM) and maleic anhydride (MA) were used as modifying monomers. The products of performed modification has been investigated by FTIR, DSC and TG methods. Modified fillers have been used in compositions with polyethylene (LDPE). Structure of the samples has been investigated by the SEM method. Mechanical properties of selected samples have been studied and discussed. The optimal results depends on dose level which is specific for certain monomers, ratio and type of monomers used and for grafting process. This paper presents data released to influence the type of monomer on properties of grafted filler. The obtained samples of filling polyethylene were characterized generally by better dispersibility and some mechanical properties.     

Metal binding and interdomain thermodynamics of mammalian metallothionein-3: enthalpically favoured Cu+ supplants entropically favoured Zn2+ to form Cu4+ clusters under physiological conditions

Metallothioneins (MTs) are a ubiquitous class of small metal-binding proteins involved in metal homeostasis and detoxification. While known for their high affinity for d¹⁰ metal ions, there is a surprising dearth of thermodynamic data on metals binding to MTs. In this study, Zn²⁺ and Cu⁺ binding to mammalian metallothionein-3 (MT-3) were quantified at pH 7.4 by isothermal titration calorimetry (ITC). Zn²⁺ binding was measured by chelation titrations of Zn₇MT-3, while Cu⁺ binding was measured by Zn²⁺ displacement from Zn₇MT-3 with competition from glutathione (GSH). Titrations in multiple buffers enabled a detailed analysis that yielded condition-independent values for the association constant (K) and the change in enthalpy (ΔH) and entropy (ΔS) for these metal ions binding to MT-3. Zn²⁺ was also chelated from the individual α and β domains of MT-3 to quantify the thermodynamics of inter-domain interactions in metal binding. Comparative titrations of Zn₇MT-2 with Cu⁺ revealed that both MT isoforms have similar Cu⁺ affinities and binding thermodynamics, indicating that ΔH and ΔS are determined primarily by the conserved Cys residues. Inductively coupled plasma mass spectrometry (ICP-MS) analysis and low temperature luminescence measurements of Cu-replete samples showed that both proteins form two Cu₄⁺–thiolate clusters when Cu⁺ displaces Zn²⁺ under physiological conditions. Comparison of the Zn²⁺ and Cu⁺ binding thermodynamics reveal that enthalpically-favoured Cu⁺, which forms Cu₄⁺–thiolate clusters, displaces the entropically-favoured Zn²⁺. These results provide a detailed thermodynamic analysis of d¹⁰ metal binding to these thiolate-rich proteins and quantitative support for, as well as molecular insight into, the role that MT-3 plays in the neuronal chemistry of copper.

Metallothioneins (MTs) are a ubiquitous class of small metal-binding proteins involved in metal homeostasis and detoxification.