A homologous series of eunicellin-based diterpenes from Acalycigorgia sp. characterised by tandem mass spectrometry

The discovery and structure determination of a homologous series of eunicellin-based diterpenes from the gorgonian Acalycigorgia sp. is described. Extensive use was made of 1D and 2D NMR data to determine the structure of the diterpene skeleton. The relative stereochemistry was confirmed via the use of NOE data in conjunction with molecular modelling. A series of homologues were identified using a combination of product and precursor ion scanning modes in tandem mass spectrometry. This powerful technique afforded excellent clarification to aid the analysis of the complex mass spectral data.     

Enantioselectivity and cis/trans-Selectivity in Dirhodium(II)-Catalyzed addition of diazoacetates to olefins

The Rh¹¹-catalyzed carbenoid addition of diazoacetates to olefins was investigated with [Rh₂{(4S)-phox}₄] ( 1 ;phox = tetrakis[(4S)-tetrahydro-4-phenyloxazol-2-one]), [Rh₂{(2S)-mepy}₄] ( 2 ; mepy = tetrakis[methyl (2S)-tetrahydro-5-oxopyrrole-2-carboxylate]), and [Rh₂(OAc)₄] ( 3 ). While catalysis with 2 and 3 afford preferentially trans-cyclopropanecarboxylates, the cis-isomers are the major products with 1 . In general, the enantioselectivities achieved with 1 and 2 are comparable. Additions catalyzed by 1 are strongly sensitive to steric effects. Highly substituted olefins afford cyclopropanes in only poor yield. The preferential cis-selectivity observed in reactions catalyzed by 1 is attributed to dominant interactions between the ligand of the catalyst and the substituents of both olefin and diazoacetate, which overrule the steric interactions between olefin and diazoacetate in the transition state for carbene transfer.     

Reporting of variations in the natural isotopic composition of mercury

High-precision measurements of natural variations in the stable isotopic composition of mercury show great promise as a new tracer of mercury sources and chemical transformations in the environment. We strongly suggest that all laboratories adopt a common means of data correction, standardization, and nomenclature in order to ensure that data from various laboratories can be easily evaluated and compared. We make suggestions for mass bias correction, reporting of mass-dependent and mass-independent isotope variations, and a standard protocol for reporting analytical uncertainties. We also present our measured values for isotope ratios in several mercury standard solutions.     

Small-molecule fluorophores to detect cell-state switching in the context of high-throughput screening

A small molecule capable of distinguishing the distinct states resulting from cellular differentiation would be of enormous value, for example, in efforts aimed at regenerative medicine. We screened a collection of fluorescent small molecules for the ability to distinguish the differentiated state of a mouse skeletal muscle cell line. High-throughput fluorescence-based screening of C2C12 myoblasts and myotubes resulted in the identification of six compounds with the desired selectivity, which was confirmed by high-content screening in the same cell states. The compound that resulted in the greatest fluorescence intensity difference between the cell states was used as the screening agent in a pilot screen of 84 kinase inhibitors, each present in four doses, for inhibition of myogenesis. Of the kinase inhibitors, 17 resulted in reduction of fluorescence at one or more concentrations; among the "hits" included known inhibitors of myogenesis, confirming that this compound is capable of detecting the differentiated myotube state. We suggest that the strategy of screening for screening agents reported here may be extended more broadly in the future.     

Analysis of transition-metal acetylacetonate complexes by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Transition-metal acetylacetonate complexes of the form Metal(acac)(2), where Metal = Fe(II), Co(II), Ni(II), Cu(II), and Zn(II), and Metal(acac)(3), where Metal = V(III), Cr(III), Mn(III), Fe(III), and Co(III), were investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The data was acquired using the aprotic, electron transfer matrix, 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB), and the observation of positive radical ions is shown clearly to depend on the metal element and the oxidation state it occupies. The ionization energy of DCTB was calculated to be 8.08 eV by density functional theory methods, which is notably lower than the experimental value, but within the range of other computational values. This value is very close to those of the analytes, so the existing electron transfer mechanism which is based on the ionization energies of the matrix and analyte, cannot be used predictively. Similarly, the data neither proves nor disproves the validity of the existing electron transfer ionization mechanism, with respect to metal coordination complexes without strong chromophores. In this case, periodic trends may be more useful in explaining the observed species and the prediction of species from sets of similar complexes. The addition of a sodium salt benefits the MALDI-TOFMS characterization of certain compounds studied, but the benefit of the addition of ammonium or silver salts is negligible.     

Block liposomes from curvature-stabilizing lipids: connected nanotubes, -rods, or -spheres

We report on the discovery of block liposomes, a new class of chain-melted (liquid) vesicles, with membranes comprised of mixtures of the membrane-curvature-stabilizing multivalent lipid MVLBG2 of colossal charge +16 e and neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). In a narrow MVLBG2 composition range (8-10 mol%), cryo-TEM revealed block liposomes consisting of distinctly shaped, yet connected, nanoscale spheres, pears, tubes, or rods. Unlike typical liposome systems, where spherical vesicles, tubular vesicles, and cylindrical micelles are separated on the macroscopic scale, within a block liposome, shapes are separated on the nanometer scale. Diblock (pear-tube) and triblock (pear-tube-pear) liposomes contain nanotubes with inner lumen diameter of 10-50 nm. Diblock (sphere-rod) liposomes were found to contain micellar nanorods approximately 4 nm in diameter and several micrometers in length, analogous to cytoskeletal filaments of eukaryotic cells. Block liposomes may find a range of applications in chemical and nucleic acid delivery and as building blocks in the design of templates for hierarchical structures.     

Crystallization and orientation of isotactic poly(propylene) in cylindrical nanopores

The crystallization of polymers in cylindrical geometries is important as interest in polymer nanowires and nanostructures grows. Here, semicrystalline isotactic poly(propylene) (iPP) is shown to crystallize in a homogeneous, low‐dimensional fashion when confined in cylindrical pores as small as 15 nm. A strong dependence on pore diameter is demonstrated. Isothermal crystallization studies suggest a reduced Avrami exponent as pore diameter decreases and as crystallization time increases. Complementary X‐ray diffraction with tilt (texture analysis) reveals one‐dimensional ordering of iPP crystals within pores of 40 nm diameter or less in which crystals preferentially orient, perpendicular to the pore wall. These findings demonstrate that the origin of this orientation is related to the impingement of crystals against the pore wall, thus “freezing out” polymer crystallizing in nonpreferred directions. These results show that curvature‐directed crystallization is one potential means to control a polymer's crystallization rate and orientation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1412–1419     

A concise synthesis of the aporhoeadane skeleton

A concise synthesis of the isoindolobenzazepine aporhoeadane core is achieved in four steps from homoveratrylamine and ninhydrin.