Practical asymmetric synthesis of alpha-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines

[reaction: see text] 2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor.     

Full Nuclear Cones and a Relation Between Strong Optimization and Pareto Efficiency

In this paper we present some new and pertinent connections between the Strong Optimization and the Approximate Pareto type Efficiency, in particular, with the usual Vector Optimization, at first in the Ordered Vector Spaces by the natural Convex Cones and, afterwards, in the Ordered Hausdorff Locally Convex Spaces. The main result is obtained considering the notion of full nuclear cone. Our results, is related to an appropriate scalarization method Mathematics Subject Classification (2000). 90C29     

Electrophilic cyclization of α-series monoterpene ω-derivatives

New information is discussed concerning the protic and Lewis acid-initiated electrophilic cyclization reaction of -monoterpenols and their acetates; the distinguishing feature of these reactions is their termination by isopropenyl residues in these molecules. The reactions have been found to be general in nature, given additional functionalization of the terminator by chloro-, sulfonyl, sulfonylmethyl, or ester substituents. Cyclization of these linear substrates has also been shown to provide a convenient method for the synthesis of dimethylvinylcyclohexene derivatives and related cyclohexanediols, which are not readily available by other methods.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1361–1367, June, 1990.     

Mass spectra of vinyltrimethylsilane and vinyltri(methyl-d3) silane

This paper reports the mass spectrum of vinyltrimethylsilane over the range of electron-impact energy of 9 to 70 eV as determined with a quadrupole mass spectrometer. Less extensive data obtained with magnetic spectrometers are included for comparison as well as the spectrum of vinyl-tri(methyl-d₃)silane. Plots of ion intensity as a function of electron energy, nominal appearance potentials and metastable ion transitions are given. The primary ionization results in an electron deficiency on the silicon atom, followed by loss of either ·CH₃, C₂H₄ or ·C₂H₃ to give fragments of mass 85, 73 or 72, respectively. The primary fragment of mass 85 loses C₂H₂ to give the mass 59 ion. The primary fragment of mass 73 loses successively C₂H₄ and H₂ to give first the mass 45 ion and then the mass 43 ion. At 15 eV, the relative intensities of the ions are 85 > 72 > 100 > 59 > 73. At 70 eV, the relative intensities are 59 > 85 > 43 > 45 > 73 > 72 > 100.     

α-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells

Background  

Oxidative stress has been proposed to be involved in the pathogenesis of Parkinson's disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species. α-Synuclein, a protein found in Lewy bodies characteristic of PD, is also thought to be involved in the pathogenesis of PD and point mutations and multiplications in the gene coding for α-synuclein have been found in familial forms of PD.     

Raman and SERS study of metoclopramide at different pH values

Conjugate acid–base forms of the drug metoclopramide were investigated by Raman spectroscopy in aqueous solutions and by surface‐enhanced Raman scattering (SERS), when the molecules were adsorbed on colloidal silver surfaces. Raman spectra were recorded at pH values below 8, metoclopramide being poorly water soluble at higher pH values. The SERS spectra of metoclopramide were recorded in the 3–11 pH range, even in spite of its low solubility at basic pH values. The Raman and SERS spectra were assigned by means of density functional theory (DFT) calculations. By monitoring several SERS marker bands, the protonated, neutral or the coexistence of both molecular species adsorbed on the colloidal silver particles could be evidenced. The adsorbate orientation was deduced to be perpendicular to the metal surface for the protonated molecular species and tilted for the neutral metoclopramide molecular species. Copyright © 2009 John Wiley & Sons, Ltd.     

Improved density functional theory/electrostatic calculation of the His291 protonation state in cytochrome C oxidase: self-consistent charges for solvation energy calculation

The protonation state of His291 in cytochrome c oxidase (CcO), a ligand to the Cu(B) center of the enzyme, has been recently studied in this group by using combined density functional theory (DFT)/electrostatic (QM/MM) calculations. On the basis of these calculations, a model of the proton pumping mechanism of CcO has been proposed. Due to certain technical difficulties, the procedure used in the previous calculation to find partial atomic charges of the QM system for the solvation energy evaluation was not entirely satisfactory; i.e., it was not self-consistent. Here, we describe a procedure that resolves the problem and report on the improved calculations of the protonation state of the His residue. The new procedure fits the protein and reaction field potentials in the region of the QM system with artificial point charges placed on a surface of a sphere surrounding the QM system and a few charges inside the sphere and allows one to perform DFT calculations that involve an inhomogeneous dielectric environment in a self-consistent way. The procedure improves the accuracy of calculations in comparison with previous work. The improved results show, however, that although the absolute energies change significantly the relative energies of the protonated and deprotonated states of His291 remain close to the previously reported ones and therefore do not change significantly the pK(a) values reported earlier. Therefore, our new improved calculations support for the proposed His291 model of the CcO pump.     

Collision and escape orbits in a generalized Hénon–Heiles model

The motion of a material point of unit mass in a field determined by a generalized Hénon–Heiles potential $U=A{q}_1^2+B{q}_2^2+C{q}_1^2{q}_2+D{q}_2^3$, with $(q_1,q_2)=$ standard Cartesian coordinates and $(A,B,C,D)\in {(0,\infty )}^2\times R^2$, is addressed for two limit situations: collision and escape. Using McGehee-type transformations, the corresponding collision and infinity boundary manifolds pasted on the phase space are determined. These are fictitious manifolds, but, due to the continuity with respect to initial data, their flow determines the near by orbit behaviour.The dynamics on the collision and infinity manifolds is fully described. The topology of the flow on the collision manifold is independent of the parameters. In the full phase space, while spiraling collision orbits are present, most of the orbits avoid collision. The topology of the flow on the infinity manifold changes as the ratio between $C$ and $D$ varies. More precisely, there are two symmetric pitchfork bifurcations along the line $2C?3D=0$, due to the reshaping of the potential along the bifurcation line. Besides rectilinear and spiraling orbits, the near-escape dynamics includes oscillatory orbits, for which angular momentum alternates sign.     

Association Phenomena of Poly(arylene ether sulfone)s in Dimethylformamide

Three poly(arylene ether sulfone)s (two polymers and one copolymer) containing diphenylfluorene, phenolphthalein and 2,4-bis[(4-chlorophenyl)sulfonyl]-1-(phenyltio) benzene)] units were synthesized by the classical Williamson polyetherification reaction. The association phenomenon in N,N-dimethylformamide (DMF) was investigated by different methods: gel permeation chromatography (GPC), viscosity, atomic force microscopy (AFM), fluorescence spectroscopy and dynamic light scattering (DLS). Both AFM and DLS measurements evidenced the formation of aggregates with spherical or ellipsoidal shape at a concentration around 0.05 wt.%. This behavior could be explained by dipole-dipole interactions between macromolecular chains, probably with the participation of solvent molecules, and by H-bonds involving hydroxyl end groups.     

Stress Integration of the Hoek-Brown Material Model Using Incremental Plasticity Theory

This paper presents the formulation of the stress integration procedure for the Hoek-Brown (HB) material model with non-associative yielding condition by using the incremental plasticity method. Main idea of this method is to reach the solution by calculating the plastic matrix according to the method of incremental plasticity (used for elastic constitutive matrix corrections), and with the use of the total strain increment. Computational procedure is implemented within the PAK program package. Results of this procedure were compared with the solutions obtained by other program that contains this material model. (© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)