Palladium Catalyzed Allylic C-H Alkylation:A Mechanistic Perspective

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Homology Modeling, Docking and Comparative Study of the Selectivity of Some Hdac Inhibitors on Pfhdac-1 and hHdac 8 Models

Malaria, one of the problems in many developing countries is caused by the  protozoan parasite called Plasmodium and several cases of the disease are reported annually. The emergence of multi-drug resistant malarial parasites necessitates the exploration of novel and promising antimalarial enzyme drug target called Plasmodium falciparum histone deacetylase 1 (PfHDAC-1). Thus, in this study, a ligand refined homology model of PfHDAC-1 was generated from the crystal structures of human HDAC8 and HDLP using a restraint guided optimization procedure involving the OPLS/GBSA potential setup. The model was validated using protein structure validation tools. A predictive docking study was carried out using nine sets of known HDAC inhibitors, which have been shown experimentally to have in vitro antimalarial activity against a strain of P. falciparum. Pose validation and score-based active and inactive separation studies provided independent validation of the geometric accuracy and the predictive ability of the generated model. Stereo chemical evaluation using Ramachandran plot revealed that 96.5% residues of the constructed model lie in the most favored and allowed regions, thus, suggesting a good quality model. Comparative analysis was carried out with the human HDAC 8 to ascertain the degree of selectivity of the inhibitors for both models. This revealed that YC-II-88 inhibitor was most selective for PfHDAC-1 model and showed no inhibitory activity for the human HDAC8 model. Keywords Homology modeling; Plasmodium falciparum; Histone deacetylase; Docking; Inhibito

Triangular prism-shaped β-peptoid helices as unique biomimetic scaffolds

β-Peptoids are peptidomimetics based on N-alkylated β-aminopropionic acid residues (or N-alkyl-β-alanines). This type of peptide mimic has previously been incorporated in biologically active ligands and has been hypothesized to be able to exhibit foldamer properties. Here we show, for the first time, that β-peptoids can be tuned to fold into stable helical structures. We provide high-resolution X-ray crystal structures of homomeric β-peptoid hexamers, which reveal right-handed helical conformations with exactly three residues per turn and a helical pitch of 9.6–9.8 Å between turns. The presence of folded conformations in solution is supported by circular dichroism spectroscopy showing length- and solvent dependency, and molecular dynamics simulations provide further support for a stabilized helical secondary structure in organic solvent. We thus outline a framework for future design of novel biomimetics that display functional groups with high accuracy in three dimensions, which has potential for development of new functional materials

Enantioselective γ-lactam synthesis via palladium-catalyzed intramolecular asymmetric allylic alkylation

A Pd(0)-catalyzed intramolecular allylic alkylation in the presence of (R)-3,5-t-Bu-MeOBIPHEP takes place in up to 92:8 er in agreement with DFT calculations and provides easy access to enantioenriched disubstituted γ-lactams

Vertical Integration and Fuel Diversity in Electricity Generation – a theoretical study in imperfect competition

This paper contains an analysis of stylised natural gas and electricity supply sectors. Power plants operate either on natural gas or on a competing fuel – e.g. oil. The competing fuel is assumed to be traded at world market price whereas natural gas is sold by a national monopoly. The paper conducts a number of analyses using different market structures, ranging from perfect competition, over oligopolistic competition among power plants using natural gas only, to situations with both gas and oil and vertical integration in the natural gas part of the sector. The paper provides a number of results, some of which are quite surprising: (1) The natural gas monopoly price is only vaguely correlated with the oil price although the fuels are competing; (2) A merger between the gas supplier and a gas-fired power plant is likely to increase social welfare, and consumer surplus; and (3) Competition between fuels has more positive effect on social welfare than increased competition between gas-fired plants