Amidrazones 9. Convenient Syntheses of 1-Alkyl-1-Phenylhydrazines and α,β-Unsaturated Amidrazones Via Base-Promoted Reactions of 1,1-Disubstituted-3-Amino-4,5-Dihydro-1H-Pyrazolium Salts

A simple, efficient procedure for the conversion of phenylhydrazine to 1-alkyl-1-phenylhydrazines via base-promoted hydrolysis of 1-alkyl-3-amino-4,5-dihydro-1-phenyl-1H-pyrazolium iodides (2) is described. N¹, N¹-disubstituted hydrazones of trans-cinnamamide and acrylamide are obtained by Hofmann-type ring openings of 1,1 -disubstituted-3-amino-4,5-dihydro-5-phenyl (or 5-unsubstituted) -1H-pyrazolium halides (5, 7).     

Photokinetic,Biochemical and Structural Features of Chimeric Photoactive Yellow Protein Constructs

Of the 10 photoactive yellow protein (PYPs) that have been characterized, the two from Rhodobacter species are the only ones that have an additional intermediate spectral form in the resting state (λ_max = 375 nm), compared to the prototypical Halorhodospira halophila PYP. We have constructed three chimeric PYP proteins by replacing the first 21 residues from the N‐terminus (Hyb1PYP), 10 from the β4–β5 loop (Hyb2PYP) and both (Hyb3PYP) in Hhal PYP with those from Rb. capsulatus PYP. The N‐terminal chimera behaves both spectrally and kinetically like Hhal PYP, indicating that the Rcaps N‐terminus folds against the core of Hhal PYP. A small fraction shows dimerization and slower recovery, possibly due to interaction at the N‐termini. The loop chimera has a small amount of the intermediate spectral form and a photocycle that is 20 000 times slower than Hhal PYP. The third chimera, with both regions exchanged, resembles Rcaps PYP with a significant amount of intermediate spectral form (λ_max = 380 nm), but has even slower kinetics. The effects are not strictly additive in the double chimera, suggesting that what perturbs one site, affects the other as well. These chimeras suggest that the intermediate spectral form has its origins in overall protein stability and solvent exposure.     

Ultra-lightweight paper foams: processing and properties

A methodology for producing a low density cellulose-based foam has been developed by combining a surfactant with pulp, mixing at high velocity to entrain air, and then drying in a non-restrained fashion. The structure of the foam, characterized through optical microscopy and X-ray computed tomographic microscopy, consists of pulp fibres in random orientations surrounding air bubbles along with large void spaces. Through careful design of experiments, the effect of fibre type, length distribution, surfactant, and air content on the mechanical behavior and permeability of the foam material was investigated. The results indicate that foamed cellulose materials can be produced at a strength of one-half the tensile strength of a standard handsheet, but having a relative density of only one percent. No chemical additives were used to enhance the strength of these samples as the properties of the foam material are enhanced simply through variation of the process parameters. Thus, a strong cellulose-based foam, with a density as low as 10 mg/cm³, can be fabricated using standard papermaking infrastructure and hence at low cost.     

Blind prediction of HIV integrase binding from the SAMPL4 challenge

Here, we give an overview of the protein-ligand binding portion of the Statistical Assessment of Modeling of Proteins and Ligands 4 (SAMPL4) challenge, which focused on predicting binding of HIV integrase inhibitors in the catalytic core domain. The challenge encompassed three components—a small “virtual screening” challenge, a binding mode prediction component, and a small affinity prediction component. Here, we give summary results and statistics concerning the performance of all submissions at each of these challenges. Virtual screening was particularly challenging here in part because, in contrast to more typical virtual screening test sets, the inactive compounds were tested because they were thought to be likely binders, so only the very top predictions performed significantly better than random. Pose prediction was also quite challenging, in part because inhibitors in the set bind to three different sites, so even identifying the correct binding site was challenging. Still, the best methods managed low root mean squared deviation predictions in many cases. Here, we give an overview of results, highlight some features of methods which worked particularly well, and refer the interested reader to papers in this issue which describe specific submissions for additional details.     

An Isserlis’ Theorem for Mixed Gaussian Variables: Application to the Auto-Bispectral Density

This work derives a version of Isserlis’ theorem for the specific case of four mixed-Gaussian random variables. The theorem is then used to derive an expression for the auto-bispectral density for quadratically nonlinear systems driven with mixed-Gaussian iid noise. C.C. Olson is a NRC Postdoctoral Research Associate.     

Thermochemistry of Binding of Lead(II) and Cadmium(II) by Saccharides in Aqueous Solution

Solution calorimetry was used to determine enthalpies and stability constants for binding of lead(II) or cadmium(II) by galacturonic acid and several monosaccharides in aqueous solution. New values for enthalpies of solution in water are reported for galacturonic acid and maltose monohydrate. The interaction of water solvent with the reactants is the largest factor in the binding process.     

Halophilic reactions of a stable silylene with chloro and bromocarbons

A number of disilanes have been synthesized from a stable silylene, 1 (N,N'-di-tert-butyl-1,3-diaza-2-silacyclopent-4-en-2-ylidene), and a variety of halocarbons. It is proposed that disilane formation is a result of an initial halophilic interaction between the silylene and halocarbon. Formation of disilanes from 1 and CCl4, 2a, CHCl3, 2b, CH2Cl2, 2c, benzyl chloride, 2d, and bromobenzene, 5, are described here. An X-ray crystal structure of 2b was determined.     

Bending of DNA by asymmetric charge neutralization: all-atom energy simulations

DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups either charge-neutralized or substituted by neutral methylphosphonates across the major or minor groove have been subjected to energy minimization to determine the conformational effect of the asymmetric elimination of phosphate charge. We report bending angles, directions of bending, and detailed structural characteristics such as groove widths and local base-pair parameters. Our principal results are that charge neutralization on one face of the DNA induces significant bending toward the neutralized face, in agreement with theoretical predictions on a simplified model and experimental data on a similar base-pair sequence, and that the DNA conformation averaged over all stereospecific methylphosphonate substitutions is nearly the same as the conformation produced by charge neutralization of the phosphates. Individual isomers, however, cover a wide range of structures, with the magnitude and direction of overall bending sensitive to the precise stereochemical pattern of neutralization. Our simulation does not explicitly contain counterions, and the results therefore suggest that counterions can influence DNA structure by neutralizing the phosphate charge. These data provide new hints into the molecular mechanisms which underlie the deformations of DNA structure induced by the binding of positively charged proteins and other tightly associated cationic species.     

Conformation-dependent state selectivity in O-O cleavage of ONOONO: an "inorganic cope rearrangement" helps explain the observed negative activation energy in the oxidation of nitric oxide by dioxygen

ONOONO has been proposed as an intermediate in the oxidation of nitric oxide by dioxygen to yield nitrogen dioxide. The O-O bond breaking reactions of this unusual peroxide, and subsequent rearrangements, were evaluated using CBS-QB3 and B3LYP/6-311G hybrid density functional theory. The three stable conformers (cis,cis-, cis,trans-, and trans,trans-ONOONO, based on the O-N-O-O dihedral angles of either approximately 0 degrees or approximately 180 degrees ) are predicted to have very different O-O cleavage barriers: 2.4, 13.0, and 29.8 kcal/mol, respectively. These large differences arise because bond breaking leads to correlation of the nascent NO(2) fragments with either the ground (2)A(1) state or the excited (2)B(2) state of NO(2), depending on the starting ONOONO conformation. A cis-oriented NO(2) fragment correlates with the (2)A(1) state, whereas a trans-oriented NO(2) fragment correlates with the (2)B(2) state. Each NO(2) fragment that correlates with (2)A(1) lowers the O-O homolysis energy by approximately 15 kcal/mol, similar to the approximately 17-25 kcal/mol (2)A(1) --> (2)B(2) energy difference in NO(2). Hence, this provides an unusual example of conformation-dependent electronic state selectivity. The O-O bond homolysis of cis,cis-ONOONO is particularly interesting because it has a very low barrier and arises from the most stable ONOONO conformer, and also due to obvious similarities to the well-known [3,3]-sigmatropic shift of 1,5-hexadiene, i.e., the Cope rearrangement. As an additional proof of our state selectivity postulate, a comparison is also made to breakage of the O-O bond of cis,cis-formyl peroxide, where no significant stabilization of the transition state is available because the (2)A(1) and (2)B(2) states of formyloxy radical are near-degenerate in energy. In the case of trans,trans-ONOONO, the O-O bond breaking transition state is a concerted rearrangement yielding O(2)NNO(2), whereas for cis,cis- and cis,trans-ONOONO, the initially formed NO(2) radical pairs can undergo further rearrangement to yield ONONO(2). It is proposed that previous spectroscopic observations of certain N=O stretching frequencies in argon-matrix-isolated products from the reaction of NO with O(2) (or (18)O(2)) are likely from ONONO(2), not the OONO radical as reported.     

Colloidal dynamics on disordered substrates

Using Langevin simulations, we examine driven colloids interacting with quenched disorder. For weak substrates the colloids form an ordered state and depin elastically. For increasing substrate strength, we find a sharp crossover to inhomogeneous depinning and a substantial increase in the depinning force, analogous to the peak effect in superconductors. The velocity versus driving force curve shows criticality at depinning, with a change in scaling exponent occurring at the order to disorder crossover. Upon application of a sudden pulse of driving force, pronounced transients appear in the disordered regime which are due to the formation of long-lived colloidal flow channels.