Predicting the reaction mechanism of nucleophilic substitutions at carbonyl and thiocarbonyl centres of esters and thioesters

In nucleophilic substitution reactions at carbonyl centres, there are two possible channels. The first one occurs when the attack of nucleophilic agents takes place simultaneously with the departure of the nucleofuge. This process is named as concerted. The second possibility is the formation of a reaction intermediate, typically a tetrahedral intermediate from which the nucleofuge departs after passing through a second transition state. This second mechanism is defined as stepwise. Whether a concerted or stepwise mechanism is to be expected for a given reaction depends on several factors. Among these determinants are the nucleophilicity of the attacking group, the leaving group ability of the nucleofuge, and the solvent, which affects both the stability of the intermediate or the transition states involved. The role of the electrophilic centre can however become an important factor that can determine the reaction mechanism. In this work we show that the group nucleophilic Fukui function model may be used to rationalize and to predict the reaction mechanism of the title compounds towards alicyclic amines. In general, when the electrophilic carbon centre is attached to the soft sulfur atom, the reaction mechanism is predicted to follow a stepwise route. When the electrophilic carbon atom is attached to a harder oxygen centre, the reaction mechanism is determined by chemical substitution at the nucleofuge moiety. Experimental verification for a set of four substrates is presented. Copyright © 2012 John Wiley & Sons, Ltd.     

Production and Characterization of Nanostructured Powders of Nd2Fe14B and Fe90Al10 by Mechanical Alloying

The objective of this work is to evaluate the applicability of exchange coupling between nanoparticles of Nd₂Fe₁₄B (hard magnetic material) and Fe₉₀Al₁₀ (soft magnetic material), as permanent magnets produced by surfactant-assisted mechanical alloying. The obtained powders were then mixed with 85% of the Nd₂Fe₁₄B system and 15% of the Fe₉₀Al₁₀ system and subsequently sintered at 300 °C, 400 °C and 500 °C for one hour. The results obtained by Mössbauer spectrometry (MS) show a ferromagnetic behavior with six magnetic sites represented by sextets (16k1, 16k2, 8j1, 8j2, 4c and 4e), characteristic of the Nd₂Fe₁₄B system. X-ray diffraction (XRD) results show a tetragonal and BCC structure for the Nd₂Fe₁₄B and FeAl systems, respectively. The results obtained by vibrating sample magnetometry (VSM), for mixtures of the Nd₂Fe₁₄B and Fe₉₀Al₁₀ sy stems sintered at 300 °C, 400 °C and 500 °C, allow for the conclusion that the coercive field (Hc) decreases drastically with temperature and the percentage of soft phase at values of Hc = 132 Oe compared to the coercive field values reported for Nd₂Fe₁₄B Hc = 6883 Oe, respectively. Images obtained by transmission electron microscopy (TEM), for the Fe₉₀Al₁₀ system, show a tendency for the nanoparticles to agglomerate.     

[As3M(As3Pb3)]3-(M =Nb,Ta):Ternary Heterometallic Clusters with Early Transition Metal Atoms and Aromatic [Pb3]2-

Main observation and conclusion Two ternary clusters,[As3Nb(As3Pb3)]3-1 and [As3Ta(As3Pb3)]3-2,were directly extracted from "K8NbPbAs5" and "K8TaPbAs5" inter-me...     

Glycan-Induced Protein Dynamics in Human Norovirus P Dimers Depend on Virus Strain and Deamidation Status

Noroviruses are the major cause of viral gastroenteritis and re-emerge worldwide every year, with GII.4 currently being the most frequent human genotype. The norovirus capsid protein VP1 is essential for host immune response. The P domain mediates cell attachment via histo blood-group antigens (HBGAs) in a strain-dependent manner but how these glycan-interactions actually relate to cell entry remains unclear. Here, hydrogen/deuterium exchange mass spectrometry (HDX-MS) is used to investigate glycan-induced protein dynamics in P dimers of different strains, which exhibit high structural similarity but different prevalence in humans. While the almost identical strains GII.4 Saga and GII.4 MI001 share glycan-induced dynamics, the dynamics differ in the emerging GII.17 Kawasaki 308 and rare GII.10 Vietnam 026 strain. The structural aspects of glycan binding to fully deamidated GII.4 P dimers have been investigated before. However, considering the high specificity and half-life of N373D under physiological conditions, large fractions of partially deamidated virions with potentially altered dynamics in their P domains are likely to occur. Therefore, we also examined glycan binding to partially deamidated GII.4 Saga and GII.4 MI001 P dimers. Such mixed species exhibit increased exposure to solvent in the P dimer upon glycan binding as opposed to pure wildtype. Furthermore, deamidated P dimers display increased flexibility and a monomeric subpopulation. Our results indicate that glycan binding induces strain-dependent structural dynamics, which are further altered by N373 deamidation, and hence hint at a complex role of deamidation in modulating glycan-mediated cell attachment in GII.4 strains.