Regiodivergent and Stereoselective Hydrosilylation of 1,3‐Disubstituted Allenes

Methods for the highly stereoselective and regiodivergent hydrosilylation of 1,3‐disubstituted allenes have been developed. The synthesis of E allylsilanes is accomplished with palladium NHC catalysts, and trisubstituted Z alkenylsilanes are accessed with nickel NHC catalysts. Unsymmetrically substituted allenes are well tolerated with nickel catalysis and afford Z alkenylsilanes. Evidence for a plausible mechanism was obtained through an isotopic double‐labeling crossover study.     

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti‐Cancer Properties

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti‐fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF‐1α) as the primary target for this compound class. Nannocystin A ( 1 ) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti‐cancer compound didemnin B on EF‐1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.     

Synthesis and Evaluation of GdIII‐Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate‐Specific Membrane Antigen

Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight Gd^III‐based PSMA‐targeted contrast agents containing one to three Gd^III chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging.     

Radical Formation in the Gas‐Phase Ozonolysis of Deprotonated Cysteine

Although the deleterious effects of ozone on the human respiratory system are well‐known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys?H]^? are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free‐radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron‐transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys‐containing peptides indicating a possible role for this chemistry in protein ozonolysis.     

The First Crystal Structure of a Reactive Dirhodium Carbene Complex and a Versatile Method for the Preparation of Gold Carbenes by Rhodium‐to‐Gold Transmetalation

The dirhodium carbene derived from bis(4‐methoxyphenyl)diazomethane and [Rh(tpa)₄]?CH₂Cl₂ (tpa=triphenylacetate) was characterized by UV, IR, and NMR spectroscopy, HRMS, as well as by X‐ray diffraction. The isolated complex exhibits prototypical rhodium carbene reactivity in that it cyclopropanates 4‐methoxystyrene at low temperature. Experimental structural information on this important type of reactive intermediate is extremely scarce and thus serves as a reference point for mechanistic discussions of rhodium catalysis in general. Moreover, dirhodium carbenes are shown to undergo remarkably facile carbene transfer on treatment with [LAuNTf₂] (L=phosphine). This formal transmetalation opens a valuable new entry into gold carbene complexes that cannot easily be made otherwise; three fully characterized representatives illustrate this aspect.     

Synthesis,Structure, and Properties of SrC(NH)3, a Nitrogen‐Based Carbonate Analogue with the Trinacria Motif

Strontium guanidinate, SrC(NH)₃, the first compound with a doubly deprotonated guanidine unit, was synthesized from strontium and guanidine in liquid ammonia and characterized by X‐ray and neutron diffraction, IR spectroscopy, and density‐functional theory including harmonic phonon calculations. The compound crystallizes in the hexagonal space group P6₃/m, constitutes the nitrogen analogue of strontium carbonate, SrCO₃, and its structure follows a layered motif between Sr²⁺ ions and complex anions of the type C(NH)₃^2?; the anions adopt the peculiar trinacria shape. A comparison of theoretical phonons with experimental IR bands as well as quantum‐chemical bonding analyses yield a first insight into bonding and packing of the formerly unknown anion in the crystal.     

Biophysical implications of bubble dynamics

Evidence is reviewed, from theory and experiment, that biological systems can be affected by ultrasound at low levels, if resonant gas bodies are present. In a suspension of cells or other particles a pulsating gas bubble causes the particles to migrate toward its surface via radiation force. This motion, in addition to acoustic microstreaming, transports particles into the bubble near-field where they are subjected to highly localized stress fields. In plant leaves containing gas-filled channels, the ultrasonic intensity required to produce cell death varies with frequency, showing minima in ranges corresponding roughly to calculated frequencies for resonance of the channels.     

Analysis methodology for 3C-PIV data of rotary wing vortices

3C-PIV data from tip vortices of either fixed-wing or rotating wing experiments are challenging from an analysis point of view. Model motion, vortex wander, spurious vectors, periodic and aperiodic effects, turbulence, and other disturbing effects are all present in the data. In most cases the vortices are not measured perpendicular to their axis as well. Engineers need time-averaged properties from the vortex in the vortex axis system for a proper modelization within simulation codes. This article describes the methods needed to deal with all the mentioned problem areas, including the conditional averaging and rotation into the vortex axis system. The methods are validated by using numerically generated vortex vector fields, and finally applied to experimental data from a hover condition of a model rotor.     

Heat transfer during dry spinning of fibers

Summary Heat transfer to fibers formed in dry spinning has been subjected to fundamental analysis. Solutions of the equation of energy have been derived and tested with experimental data. Results were deemed satisfactory in view of the accuracy of the experimental data. The present work is believed to yield a good representation of the heat transfer in the dry spinning process.Nomenclature h heat transfer coefficient, cal/cm² °C sec - k thermal conductivity, cal/cm °C sec - r radial distance, cm - t time, sec - Z axial distance, cm - A surface area, cm² - A _n or n-th root of - A ₀ energy required for solvent evaporation, cal/sec cm³ - C _p specific heat cal/gm °C - J ₀ Bessel function of first kind, order zero - J ₁ Bessel function of first kind, order one - J ₂ Bessel function of first kind, order two - N k/(R ² C _p V) - Q volumetric flow rate cm³/sec - R outside radius, cm - T point temperature, °C - T _S surface temperature °C - T ₀ initial fiber temperature °C - T ambient air temperature, °C - average fiber temperature, °C - ₁ average fiber temperature of preceding segment, °C - V average fiber velocity relative to air strean, cm/sec - V _r radial velocity component, cm/sec - V _z axial velocity components, cm/sec - V direction velocity component cm/sec - W weight of solvent evaporated in a given fiber segment, gms - _n a solution of the equation J ₀(X)=0 - heat of vaporization of solvent, cal/gm - dimension - r/R - density, gms/cc