The cationic cascade route to longifolene

W. S. Johnson's total synthesis of the sesquiterpenoid longifolene is a classic example of the power of cationic polycyclizations for constructing complex molecular architectures. Herein we revisit the key polycyclization step of this synthesis using hybrid Hartree-Fock/density functional theory calculations and validate the feasibility of Johnson's proposed mechanism. We also explore perturbations to the 3-center 2-electron bonding array in a key intermediate that result from changing the polycyclic framework in which it is embedded.     

The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4

The prion protein (PrP) binds Cu2+ in its N-terminal octarepeat domain. This unusual domain is comprised of four or more tandem repeats of the fundamental sequence PHGGGWGQ. Previous work from our laboratories demonstrates that at full copper occupancy, each HGGGW segment binds a single Cu2+. However, several recent studies suggest that low copper occupancy favors different coordination modes, possibly involving imidazoles from histidines in adjacent octapeptide segments. This is investigated here using a combination of X-band EPR, S-band EPR, and ESEEM, along with a library of modified peptides designed to favor different coordination interactions. At pH 7.4, three distinct coordination modes are identified. Each mode is fully characterized to reveal a series of copper-dependent octarepeat domain structures. Multiple His coordination is clearly identified at low copper stoichiometry. In addition, EPR detected copper-copper interactions at full occupancy suggest that the octarepeat domain partially collapses, perhaps stabilizing this specific binding mode and facilitating cooperative copper uptake. This work provides the first complete characterization of all dominant copper coordination modes at pH 7.4.     

Axisymmetric Coanda-assisted vectoring

An experimental demonstration of a jet vectoring technique used in our novel spray method called Coanda-assisted Spray Manipulation (CSM) is presented. CSM makes use of the Coanda effect on axisymmetric geometries through the interaction of two jets: a primary jet and a control jet. The primary jet has larger volume flow rate but generally a smaller momentum flux than the control jet. The primary jet flows through the center of a rounded collar. The control jet is parallel to the primary and is adjacent to the convex collar. The Reynolds number range for the primary jet at the exit plane was between 20,000 and 80,000. The flow was in the incompressible Mach number range (Mach < 0.3). The control jet attaches to the convex wall and vectors according to known Coanda effect principles, entraining and vectoring the primary jet, resulting in controllable r − θ directional spraying. Several annular control slots and collar radii were tested over a range of momentum flux ratios to determine the effects of these variables on the vectored jet angle and spreading. Two and Three-component Particle Image Velocimetry systems were used to determine the vectoring angle and the profile of the combined jet in each experiment. The experiments show that the control slot and expansion radius, along with the momentum ratios of the two jets predominantly affected the vectoring angle and profile of the combined jets.     

Measurements of roughness noise

Experiments have been performed on the roughness noise produced by a two-dimensional turbulent wall jet boundary layer flowing over short fetches of sandpaper roughness. A range of rough surface sizes were studied from hydrodynamically smooth through fully rough. Velocity measurements were made to document the form of the wall jet boundary layer and the influence of the roughness upon it. Acoustic measurements showed background noise levels to be very low so that the sound produced by the rough surfaces could be clearly detected with signal to noise ratios as large as 20 dB. Even hydrodynamically smooth roughness was found to produce noise, conclusively indicating the presence of scattering as a source mechanism. Variations of the roughness noise spectra with flow speed and roughness size are found to be inconsistent with any simple parameter scaling. Boundary layer wall pressure fluctuation measurements made within the roughness fetches reveal a spectral form quite different than the roughness noise, and fluctuation levels some 50-70 dB higher. Despite these differences the wall pressure and roughness noise are found to be very simply related, at least at lower frequencies (<6 kHz). The roughness noise spectrum varies closely as the product of the wall pressure spectrum, the frequency squared, and the mean-square roughness height. This is the scaling predicted by scattering theory and implies a major simplification to the problem of roughness noise prediction for stochastic surfaces.     

Asymmetric synthesis of methylenetetrahydrofurans by palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane with aldehydes--a novel ligand design

The palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with aldehydes is a direct and efficient route to methylenetetrahydrofurans. Herein we describe the first asymmetric synthesis of methylenetetrahydrofurans utilizing a palladium-TMM complex in the presence of a novel phosphoramidite ligand possessing a stereogenic phosphorus. The method allows for the formation of chiral disubstituted tetrahydrofurans in good yields and enantioselectivities.     

Computational design of the sequence and structure of a protein-binding peptide

The de novo design of protein-binding peptides is challenging because it requires the identification of both a sequence and a backbone conformation favorable for binding. We used a computational strategy that iterates between structure and sequence optimization to redesign the C-terminal portion of the RGS14 GoLoco motif peptide so that it adopts a new conformation when bound to Gα(i1). An X-ray crystal structure of the redesigned complex closely matches the computational model, with a backbone root-mean-square deviation of 1.1 ?.     

Perfect imaging of hypersurfaces via transformation optics

Conventional optical imaging systems suffer from the presence of many imperfections, such as spherical aberrations, astigmatism, or coma. If the imaging system is corrected for spherical aberrations and fulfills the Abbe sine condition, perfect imaging is guaranteed between two parallel planes but only in a small neighborhood of the optical axis. It is therefore worth asking for optical systems that would allow for perfect imaging between arbitrary smooth surfaces without restrictions in shape or extension. In this Letter, we describe the application of transformation optics to design refractive index distributions that allow perfect, aberration-free imaging for various imaging configurations in R(n). A special case is the imaging between two extended parallel lines in R(2), which leads to the well-known hyperbolic secant index distribution that is used for the fabrication of gradient index lenses.     

Boron trifluoride facilitated transesterification of dioxaborolanes

The direct transesterification of dioxaborolanes (alkane-1,2-diol based boronate esters) was explored. Using BF₃·OEt₂, alkane-1,2-diol based mono- and bis-boronate esters (i.e., pinacol and ethylene glycol) have been converted quantitatively to either benzene-1,2-diol or alkane-1,3-diol based boronate esters. In the case of pinacol esters, esterification is facilitated by the accompanying pinacol rearrangement, thus shifting the reaction equilibrium.