Boyd Group Electronegativity Influence on the Parr Global Electrophilicity of Vilsmeier Reagent‐Derived Imidates: New Insights toward Improving Mitsunobu Chemistry

Reactivities of 19 methylated imidate analogs were examined using B3LYP and M06‐2X DFT methods. The resulting HOMO and LUMO energies of each optimized structure were used to calculate corresponding Parr global electrophilicity (ω) values. When the resulting quantities were compared against Boyd group electronegativity (X_G) values, a clear correlation was observed, suggesting that electron‐withdrawing effects influence the reactivity of imidates. These findings represent an important first step in developing a novel method toward improving traditional Mitsunobu functionalization reactions.     

Synthesis of chiral iodo-N,O-acetonide aminal scaffolds via an efficient cascade reaction of amino acid-derived epoxides

Novel amino acid-derived iodo-N,O-acetonide aminals were developed as chiral, non-epimerizable scaffolds to facilitate complex molecule synthesis. These scaffolds are readily prepared from commercially available amino acid derivatives in ?6 steps, contain an orthogonally-protected β-hydroxy amine moiety, and feature a directly reactive alkyl-iodide group for facile substitution chemistry. Further, a novel ring opening/cyclization cascade reaction was developed to prepare these compounds efficiently (59-72%) from readily available epoxide derivatives.     

An ensemble and single-molecule fluorescence microscopy investigation of phase-separated monolayer films stained with Nile Red

Phase-separated Langmuir-Blodgett monolayer films prepared from mixtures of arachidic acid (C19H39COOH) and perfluorotetradecanoic acid (C13F27COOH) were stained via spin-casting with the polarity sensitive phenoxazine dye Nile Red, and characterized using a combination of ensemble and single-molecule fluorescence microscopy measurements. Ensemble fluorescence microscopy and spectromicroscopy showed that Nile Red preferentially associated with the hydrogenated domains of the phase-separated films, and was strongly fluorescent in these areas of the film. These measurements, in conjunction with single-molecule fluorescence imaging experiments, also indicated that a small sub-population of dye molecules localizes on the perfluorinated regions of the sample, but that this sub-population is spectroscopically indistinguishable from that associated with the hydrogenated domains. The relative importance of selective dye adsorption and local polarity sensitivity of Nile Red for staining applications in phase-separated LB films as well as in cellular environments is discussed in context of the experimental results.     

磺基水杨酸修饰电极联吡啶钌电化学发光体系测定可待因的研究

基于磷酸可待因对联吡啶钌在该电极上的电化学及其发光行为的增敏作用,建立了一种直接测定磷酸可待因的电化学发光新方法。在最佳实验条件下,磷酸可待因在1.0×10-4～4.0×10-6mol/L和4.0×10-6～2.0×10-7mol/L与相对发光强度呈线性关系,检出限为1.0×10-7mol/L(S/N=3)。连续测定4.0×10-7mol/l磷酸可待因5次,发光强度的RSD为2.7%。方法用于模拟尿样中磷酸可待因的测定,结果满意。     

Detection of small-molecule enzyme inhibitors with peptides isolated from phage-displayed combinatorial peptide libraries

BACKGROUND: The rapidly expanding list of pharmacologically important targets has highlighted the need for ways to discover new inhibitors that are independent of functional assays. We have utilized peptides to detect inhibitors of protein function. We hypothesized that most peptide ligands identified by phage display would bind to regions of biological interaction in target proteins and that these peptides could be used as sensitive probes for detecting low molecular weight inhibitors that bind to these sites. RESULTS: We selected a broad range of enzymes as targets for phage display and isolated a series of peptides that bound specifically to each target. Peptide ligands for each target contained similar amino acid sequences and competition analysis indicated that they bound one or two sites per target. Of 17 peptides tested, 13 were found to be specific inhibitors of enzyme function. Finally, we used two peptides specific for Haemophilus influenzae tyrosyl-tRNA synthetase to show that a simple binding assay can be used to detect small-molecule inhibitors with potencies in the micromolar to nanomolar range. CONCLUSIONS: Peptidic surrogate ligands identified using phage display are preferentially targeted to a limited number of sites that inhibit enzyme function. These peptides can be utilized in a binding assay as a rapid and sensitive method to detect small-molecule inhibitors of target protein function. The binding assay can be used with a variety of detection systems and is readily adaptable to automation, making this platform ideal for high-throughput screening of compound libraries for drug discovery.     

Structural and compositional mapping of a phase-separated Langmuir–Blodgett monolayer by X-ray photoelectron emission microscopy

The structure and composition of phase-separated Langmuir–Blodgett monolayer films comprised of mixtures of arachidic acid (C₁₉H₃₉COOH) and perfluorotetradecanoic acid (C₁₃F₂₇COOH) were characterized using a combination of X-ray photoelectron emission microscopy (X-PEEM), secondary electron emission microscopy (SEEM) and atomic force microscopy (AFM). X-PEEM provides high lateral spatial resolution and is directly sensitive to the elemental and chemical (functional group) composition of these ultrathin films through the chemical sensitivity of NEXAFS spectroscopy; AFM provides high-resolution imaging, both in terms of lateral and vertical (height) film topography. SEEM provides additional structural and electronic information through work function and electron scattering effects. The combination is used for chemical mapping of the phase-separated domains in the monolayer film. Our results directly confirm previous AFM measurements that suggested that the discontinuous domains are enriched in arachidic acid, whereas the surrounding continuous domain is a mixture of both arachidic acid and perfluorotetradecanoic acid.     

Kinetics of desorption of ions from quartz and mica surfaces

As part of an investigation concerning the fate of²²⁶Ra during uranium ore milling and long-term taillings storage we have investigated the kinetics of the desorption of alkaline earth, lead and sulfate ions from quartz and mica surfaces into water and dilute nitric acid using a radio-tracer technique. The retention times are sufficiently long to permit the growth of the surface deposits hypothesized in the HILEMAN-SNODGRASS model. The kinetics of desorption of most of these ions is found to agree with the model for rate-limiting desorption proposed by CEREFOLINI. In the case of the desorption of Ba²⁺ from mica surfaces the data suggest some degree of integration of the Ba²⁺ into the mica.     

Cyclopropylcarbinyl-type ring openings. Reconciling the chemistry of neutral radicals and radical anions

Cyclopropylcarbinyl --> homoallyl and related rearrangements of radical ions (a) are frequently used as mechanistic "probes" to detect the occurrence of single electron transfer in chemical and biochemical processes, (b) provide the basis for mechanism-based drug design, and (c) are important tools in organic synthesis. Unfortunately, these rearrangements are poorly understood, especially with respect to the effect of substrate structure on reactivity. Frequently, researchers assume that the same factors which govern the reactivity of neutral free radicals also pertain to radical ions. The results reported herein demonstrate that in some cases structure-reactivity trends in radical ion rearrangements are very different from neutral radicals. For radical ions, delocalizations of both charge and spin are important factors governing their reactivity.     

Total synthesis and structure confirmation of the annonaceous acetogenins 30(S)-hydroxybullatacin,uvarigrandin a,and 5(R)-uvarigrandin a (narumicin I?)

A synthesis of the bistetrahydrofuran Annonaceous acetogenins 30(S)-hydroxybullatacin, uvarigrandin A, and 5(R)-uvarigrandin A through application of a previously disclosed four-component modular approach is described in which extended core segments are coupled to a C4- or C5-hydroxy butenolide terminus. The butenolide termini segments were prepared from (S)- or (R)-malic acid. Spectral properties of synthetic 30(S)-hydroxybullatacin and uvarigrandin A, as well as their Mosher ester derivatives, were in close agreement to the reported values for the natural substances. The synthetic 5(R)-uvarigrandin A is possibly identical to narumicin I, but subtle differences in the reported NMR spectra prevented an unambiguous assessment of this point.