Molecular determinants in the bioactivation of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Summary Nineteen analogs of the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have been used as probes to study the structural parameters that influence MAO-catalyzed oxidation. In this study, the efficiency of enzyme-catalyzed substrate oxidation was found to be unrelated to parameters such as the ionization potential, dipole moment, net atomic charge at C5 and the dihedral angle between the phenyl ring and the tetrahydropyridine moiety. Conformational analysis revealed that substitution at the C2 position of MPTP yields atropisomers. It is suggested that one of these atropisomers would be either inactive or substantially less active than the other. Therefore, the relative oxidative efficiency and toxicity of these compounds reported earlier may have been significantly underestimated. Based on the conformational analysis and other data, a rudimentary model of the MAO substrate site has been developed which partially explains the substrate specificities of MAO A and MAO B.Each substrate binding site can be divided into two regions, (a) an amine-binding pocket (for the tetrahydropyridine moiety), and (b) a bulky substituent region (for the phenyl group and its substituents). The length of the substrate binding site (measured along the long axis of MPTP) is approximately 8.5 Å, and the width of the amine-binding pocket is approximately 2.5 Å (from C3 to C5). The bulky substituent region contains a central area for binding the phenyl group of MPTP. This central area is flanked by two hydrophobic pockets, P2 and P3. In MAO A, the pocket P2-A is oriented 45–135° relative to the plane of the tetrahydropyridine moiety, with a radius of 3.1 Å from C2 of the phenyl ring. The radius of a similar but smaller pocket, P2-B, in MAO B, is approximately 2.7 Å. In MAO B, the pocket P3-B (radius 2.36 Å from C3) is larger than a similar pocket P3-A (radius 1.70 Å from C3) in MAO A. The foregoing characterization suggests that differences in the size and topography of both of the substituent pockets play an important role in determining the substrate specificities of these two isozymes.     

Gas--liquid chromatographic determination of carbamazepine and phenylethylmalonamide in plasma after reaction with dimethylformamide dimethylacetal

A previously published procedure for the gas chromatographic analysis of carbamazepine has been modified and expanded to allow simultaneous determination of phenylethylmalonamide, a metabolite of primidone. Internal standards that closely resemble each compound are used, and derivatives are made by reaction with dimethylformamide dimethylacetal. This change of internal standard for carbamazepine and the use of a commercial, pretested column-packing material eliminate the major pitfalls of the original method.     

Diffusion of organic vapors at low concentrations in glassy PVC, polystyrene, and PMMA

Diffusion coefficients of various C₁ to C₆ organic vapors, at concentrations 0.5 wt. percent, have been determined by gravimetric sorption rate measurements on emulsion and suspension-polymerized powder samples of PVC, polystyrene, and PMMA. Fickian diffusion kinetics were observed at the lowest concentrations, with a second-stage, relaxation-controlled sorption appearing at higher concentrations. In conjunction with published data for diffusivities of fixed gases in these polymers, the results indicate that diffusivity decreases exponentially, and that diffusion activation energy (E_D) increases linearly, with increasing diameter of “spherical” penetrant molecules (e.g., the noble gases, CH₄, SF₆, CCl₄, and neopentane). Much of the observed scatter in these correlations is attributable to uncertainty in the molecular diameters. For C₄ and larger n-alkanes and other elongated or flattened molecules, diffusivities are higher, and E_D lower, than for spherical molecules of similar molar volume. This finding suggests that anisometric molecules are oriented and move along their long axes during diffusion through the glassy polymer matrix. Correlations of diffusivities with molecular dimensions suggests that transport of anisometric molecules is governed by a diameter smaller than the mean (equivalent sphere) diameter but larger than the minimum dimension of their extended-chain conformation. Among the three polymers studied, diffusivity of each penetrant, at a given temperature, decreases in the order polystyrene> PVC ≥ PMMA.     

An evaluation of cellulose as a substrate for room-temperature phosphorescence

Cotton-linter pulps, wood pulps and several filter papers have been evaluated as substrates for room-temperature phosphorescence. A variety of chemical treatments of one filter paper is discussed in terms of reducing the background phosphorescence of the cellulose and in evaluating possible trace contaminants in cotton fibres. In order to account for uniformity of filter paper used in room temperature phosphorescence, a final evaluation of several different lots of one type of filter paper is presented.     

Oxepinamides A-C and fumiquinazolines H--I: bioactive metabolites from a marine isolate of a fungus of the genus Acremonium

Three new oxepin-containing natural products (1-3) and two new fumiquinazoline metabolites (4-5) have been isolated from organic extracts of the culture broth and mycelia of an Acremonium sp., a fungus obtained from the surface of the Caribbean tunicate Ecteinascidia turbinata. The structures of the five compounds were determined through extensive analysis of 1D- and 2D-NMR data, and mass spectrometry. Compound 1 exhibited good anti-inflammatory activity in a topical RTX-induced mouse ear edema assay. Compounds 4 and 5 exhibited weak antifungal activity toward Candida albicans in a broth microdilution assay.     

Über Fluoride des zweiwertigen Eisens: Ba2[Fe3F10]

On the Knowledge of Ba₂[Fe₃F₁₀] For the first time colourless single crystals of Ba₂Fe₃F₁₀ have been prepared by reduction of a mixture of 3 BaF₂/7 FeF₃ in a Fe-tube (reaction with the wall 750°C, 60 d). Ba₂Fe₃F₁₀ crystallizes in the monoclinic spcgr. P2₁/c with a = 788.3(1), b = 623.0(1), c = 1868.0(3) pm, β = 111.79(1)º, Z = 4. (Fourcircle diffractometer PW 1100, Fa. Philips, MoKα, 2383 of 2383 I₀(hkl), R = 8.1%, R_w = 4.1%, parameters see in the text). The Madelung Part of Lattice Energy, MAPLE, is calculated and discussed.     

Zum Dissoziationsverhalten dimerer Metallhalogenide und zur Bildung von MnAl2Cl8

Dissoziation Behaviour of Dimerie Metal Halides and the Formation of MnAl₂Cl₈ The thermal dissoziation was measured of the gaseous dimeric metal halides Al₂Cl₆, Ga₂Cl₆, In₂Cl₆, and Mn₂I₄ and the formation of the gaseous chloride complex MnAl₂Cl₈ by MnCl_2,f and Al₂Cl_6,g in a membrane manometer. The enthalpy and the entropy of these reactions were derived.     

Continuous Selective Heating of the Dispersion Medium in a Unit Constituted by Heater and Mass-Exchange Apparatus

A new method for heat exchange between dispersed flows and a unit for continuous selective heating, comprising a heater and a mass-exchange apparatus, was proposed. A mathematical model of the unit was developed for the cases of direct-flow and counterflow heaters. Analytical solutions to the model equations were obtained. The parameters affecting the result of continuous selective heating of the dispersion medium in the unit were determined.     

Sorption Concentration of Radiocesium on NaX Zeolite Modified with Cu2[Fe(CN)6]

Sorption of ¹³⁷Cs on NaX zeolite modified with Cu₂[Fe(CN)₆] was studied under dynamic conditions.     

Iodine(V) reagents in organic synthesis. Part 3. New routes to heterocyclic compounds via o-iodoxybenzoic acid-mediated cyclizations: generality, scope, and mechanism

The discovery and development of the o-iodoxybenzoic acid (IBX) reaction with certain unsaturated N-aryl amides (anilides) to form heterocycles are described. The application of the method to the synthesis of delta-lactams, cyclic urethanes, hydroxy amines, and amino sugars among other important building blocks and intermediates is detailed. In addition to the generality and scope of this cyclization reaction, this article describes a number of mechanistic investigations suggesting a single electron transfer from the anilide functionality to IBX and implicating a radical-based mechanism for the reaction.