Tetrameric Cubic Structures of Two Solvated Lithium Enolates

The structures of the crystalline lithium enolates derived from 3, 3-dimethyl-2-butanone and from cyclopentanone have been determined by X-ray analysis. Both structures are tetrameric aggregates based on a Li₄O₄-cube, each Li⁺-ion being additionally bonded to the O-atom of a tetrahydrofuran solvent molecule.     

Triangles and tetrahedra: metal directed self-assembly of metallo-supramolecular structures incorporating bis-beta-diketonato ligands

The interaction of six aryl-linked bis-beta-diketones, including a new naphthylene linked species, with copper(II), iron(III) and, in one instance gallium(III), has been investigated with the aim of obtaining metallo-supramolecular assemblies exhibiting different geometries. New examples of two assembly types incorporating the above bis-beta-diketones (L) were generated. The first type is represented by a range of molecular triangles of formula [Cu(3)(L-H(2))(3)](solvent)(n) while the second is given by a corresponding selection of less-common neutral molecular tetrahedra of formula [Fe(4)(L-H(2))(6)](solvent)(n) as well as [Ga(4)(L-H(2))(6)].8.5THF.0.5H(2)O; an example of each type has been characterised by X-ray crystallography. A magnetochemical investigation of [Fe(4)(-H(2))(6)].6THF is reported. The susceptibility is Curie like and consistent with very weak coupling occurring between the iron(III) d(5)(high spin) centres. The X-ray structures of two trinuclear copper(II) as well as a tetranuclear iron(III) and a tetranuclear gallium(III) assembly confirm their discrete triangular and tetrahedral geometries, respectively. The structure of the gallium(III) species is closely related to that of the corresponding iron(III) species. The tetrahedral structures provide rare examples of such assemblies encapsulating guest solvent molecules--in each case tetrahydrofuran is incorporated in the central cavity.     

Application of affinity selection-mass spectrometry assays to purification and affinity-based screening of the chemokine receptor CXCR4

Affinity selection-mass spectrometry (AS-MS) is a sensitive technology for identifying small molecules that bind to target proteins, and assays enabled by AS-MS can be used to delineate relative binding affinities of ligands for proteins. 'Indirect' AS-MS assays employ size-exclusion techniques to separate target-ligand complexes from unbound ligands, and target-associated ligands are then specifically detected by liquid chromatography mass spectrometry. We report how indirect AS-MS binding assays with known reference control compounds were used as guideposts for development of an optimized purification method for CXCR4, a G-protein coupled chemokine receptor, for which we sought novel antagonists. The CXCR4 purification method that was developed was amenable to scale-up and enabled the screening of purified recombinant human CXCR4 against a large combinatorial library of small molecules by high throughput indirect AS-MS. The screen resulted in the discovery of new ligands that competed off binding of reference compounds to CXCR4 in AS-MS binding assays and that antagonized SDF1α-triggered responses and CXCR4-mediated HIV1 viral uptake in cell-based assays. This report provides a methodological paradigm whereby indirect AS-MS-based ligand binding assays may be used to guide optimal integral membrane protein purification methods that enable downstream affinity selection-based applications such as high throughput AS-MS screens.     

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1, ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.     

High-performance liquid chromatography systems for the separation of benzodiazepines and their metabolites

The high-performance liquid chromatographic (HPLC) retention characteristics of 21 benzodiazepine drugs and some of their metabolites have been examined on both silica and ODS-silica packing materials. Four HPLC systems have been considered and retention data are presented for the drugs on these systems. The correlation of retention data on the systems is considered with reference to the problem of identifying unknown benzodiazepines.     

Field-portable, high-speed GC/TOFMS

This work is focused on developing a fast gas chromatograph, time-of-flight mass spectrometer (GC/TOFMS) for man-portable field use. The goal is to achieve a total system solution for meeting performance, size, weight, power, cost, and ruggedness requirements for a laboratory in the field. The core technology will also be adaptable to specific applications including real-time point detection for hazardous chemical releases (e.g., chemical weapons), for biological agent signature identification, and for mobile monitoring platforms (e.g., air, ship, truck). Previously we presented results of a feasibility demonstration for a 30-lb field-portable TOFMS system. In this work we present recent progress in integrating a low-power, high-speed GC and show the capability for accurately recording fast GC transients for targeted compound detection using a quadrupole ion trap, time-of-flight instrument (QitTof).     

Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α‐Arylation of Alcohols through Photoredox,HAT, and Nickel Catalysis

The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α‐hydroxy C?H bonds. This approach employs zinc‐mediated alcohol deprotonation to activate α‐hydroxy C?H bonds while simultaneously suppressing C?O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn‐based Lewis acids also deactivates other hydridic bonds such as α‐amino and α‐oxy C?H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3‐step synthesis of the drug Prozac exemplifies the utility of this new method.