Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Molecular dynamics (MD) simulations were used to investigate the binding of six chiral compounds to the amino acid-based molecular micelle (MM) poly-(sodium undecyl-(L)-leucine-leucine) or poly(SULL). The MM investigated is used as a chiral selector in capillary electrophoresis. The project goal was to characterize the chiral recognition mechanism in these separations and to move toward predictive models to identify the best amino acid-based MM for a given separation. Poly(SULL) was found to contain six binding sites into which chiral compounds could insert. Four sites had similar sizes, shapes, and electrostatic properties. Enantiomers of alprenolol, propranolol, 1,1′-bi-2-naphthyl-2,2′-diyl hydrogen phosphate, 1,1′-bi-2-naphthol, chlorthalidone, or lorazepam were separately docked into each binding pocket and MD simulations with the resulting intermolecular complexes were performed. Solvent-accessible surface area calculations showed the compounds preferentially associated with binding sites where they penetrated into the MM core and shielded their non-polar atoms from solvent. Furthermore, with five of the six compounds the enantiomer with the most favorable free energy of MM association also experienced the most favorable intermolecular hydrogen bonding interactions with the MM. This result suggests that stereoselective intermolecular hydrogen bonds play an important role in chiral discrimination in separations using amino acid-based MMs.GRAPHICAL ABSTRACT     

Molecular electrotatic potential of a triple stranded helix: Poly(dT)·poly(dA)·poly(dT)

The molecular electrostatic potential of the triple helix poly(dT)·tpoly(dA)·poly(dT) is calculated, and the results are examined in relation to those obtained for its component double and single helical parts. For the double helix presenting the standard Watson–Crick hydrogen bonds, the deepest potentials are formed on the side of the major groove, a situation similar to that observed in the A-DNA duplex. For the double helix presenting Hoogsteen-type hydrogen bonds the deepest potentials lie in the major groove, on the side of the pyrimidine strand. In the triple helix the deepest potentials are located in the major groove in a narrow zone over the thymine bases of the Watson–Crick pair.     

Stereochemical assignments of the 7-phenyl-3-oxabicyclo[4.1.0]heptanes

A method for making stereochemical assignments based on nmr data for the 7-phenyl-3-oxabicyclo[4.1.0]-heptanes is described.     

Mechanism for reduction catalysis by metal oxo: hydrosilation of organic carbonyl groups catalyzed by a rhenium(V) oxo complex

The rhenium oxo complex [Re(O)(hoz)2][TFPB], 1 (where hoz = 2-(2'-hydroxyphenyl)-2-oxazoline(-) and TFPB = tetrakis(pentafluorophenyl)borate) catalyzes the hydrosilation of aldehydes and ketones under ambient temperature and atmosphere. The major organic product is the protected alcohol as silyl ether. Isolated yields range from 86 to 57%. The reaction requires low catalyst loading (0.1 mol %) and proceeds smoothly in CH2Cl2 as well as neat without solvent. In the latter condition, the catalyst precipitates at the end of reaction, allowing easy separation and catalyst recycling. Re(O)(hoz)(H), 3, was prepared, and its involvement in an ionic hydrosilation mechanism was evaluated. Complex 3 was found to be less hydridic than Et3SiH, refuting its participation in catalysis. A viable mechanism that is consistent with experimental findings, rate measurements, and kinetic isotope effects (Et3SiH/Et3SiD = 1.3 and benzaldehyde-H/benzaldehyde-D = 1.0) is proposed. Organosilane is activated via eta2-coordination to rhenium, and the organic carbonyl adds across the coordinated Si-H bond [2 + 2] to afford the organic reduction product.     

Discovery of the archaeal chemical link between glycogen (starch) synthase families using a new mass spectrometry assay

Starch and its analogue glycogen are biosynthesized by enzymes that have been classified by sequence similarities into two families that have no significant sequence overlap: the animal/fungal glycogen synthases and the plant/bacterial glycogen (starch) synthases. Recent gene sequence analysis of putative archaea enzymes implicates them as a third family that links the structural and functional features of the other two classes. Herein, we present the first rapid electrospray ionization mass spectrometry-based assay to quantify any carbohydrate-polymerizing activity, the first cloning and recombinant expression as well as verification of the putative function of a glycogen synthase from the hyperthermophilic archaea Pyrococcus furiosus, and the characterization of a variety of glycogen synthases with the new assay. The new assay allowed the determination of Km and Vmax values for the rabbit, yeast, and P. furiosus glycogen synthases. Most surprisingly, unlike the synthases from rabbit or yeast and in contradiction to what would be expected from structural studies of other nucleotide-sugar binding proteins, the synthase from the archaea source accepts both uridine- and adenine-diphosphate activated glucose competitively and with comparable affinities to form a glucose polymer. This loose substrate specificity implicates this protein as the chemical link between the two branches of glycogen synthases that have evolved to accept primarily one or the other nucleotide as well as a good source enzyme for polymer bioengineering efforts.     

The influence of pore and Ni morphology on the electrical conductivity of porous Ni/YSZ composite anodes for use in solid oxide fuel cell applications

A wide range of porous Ni–YSZ composite microstructures was produced by conventional tape casting and co-sintering using a variety of starting powders including Ni, NiO, graphite and Ni-coated graphite. The graphite additions were added to produce controlled levels of porosity in the final sintered and reduced anode. All materials indicated classical conductivity percolation behaviour with increasing Ni loadings. However, the percolation threshold at which electrical conduction became measurable was lowest for anodes made with Ni-coated graphite and highest for anodes containing large amounts of porosity introduced by large additions of graphite. Sintered and reduced anodes possessed large scale porosity introduced by the graphite additions and a finer scale porosity generated by the incomplete sintering of the Ni/YSZ powder network. A model was developed for predicting the influence of large scale porosity on conductivity and agreed well with the experimental results. The analysis indicates that fine scale porosity will have a more detrimental impact on conductivity compared to a coarse porous structure.     

Efficient microwave-assisted synthesis of 1-(1H-indol-1-yl)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents

New conazole antifungals, in the series of triazole alcohols 23a-d and 24a-e incorporating an indole moiety substituted at 5-position by halogens, a cyano or 4-methoxyphenyl group, have been synthesized by ring opening of corresponding oxiranes 15 and 16. These dihalogeno intermediates and their congeneers could be prepared in high yields by Corey-Chaykovsky reaction under microwave irradiation.