The application of multiplexed,multi‐dimensional ultra‐high‐performance liquid chromatography/tandem mass spectrometry to the high‐throughput screening of lysosomal storage disorders in newborn dried bloodspots

Lysozomal storage disorders are just beginning to be routinely screened using enzyme activity assays involving dried blood spots and tandem mass spectrometry (MS/MS). This paper discusses some of the analytical challenges associated with published assays including complex sample preparation and potential interference from excess residual substrate. Solutions to these challenges are presented in the form of on‐line two‐dimensional chromatography to eliminate off‐line liquid‐liquid extraction (LLE) and solid‐phase extraction (SPE), the use of ultra‐high‐performance liquid chromatography (UHPLC) to separate excess substrate from all other analytes and multiplexed sample introduction for higher throughput required of a population screening assay. High sensitivity, specificity and throughput were demonstrated using this novel method. Copyright © 2010 John Wiley & Sons, Ltd.     

Potentialtheorie auf dem Sierpinski gasket

Ohne Zusammenfassung     

Symmetry adapted formulation of the generalized Brillouin theorem

The singly excited functions satisfying Brillouin theorem are expressed as linear combinations of configuration-state functions for any spin and spatial symmetries (atomic or molecular) and for any reference wave function. The generality of the formulation is ensured by the use of the irreducible tensor method that can be adapted to any symmetry point group of interest. The expansion coefficients are simply written as products of fractional parentage coefficients, spin- and orbit-recoupling coefficients, and phase factors. The formalism is illustrated for some atomic (K_h) and molecular (C_∞v, C_3v, and T_d) configurations. Group theoretical techniques are also used to correlate the Brillouin conditions within a chain of groups.     

Insights into the Pamamycin Biosynthesis

Pamamycins are macrodiolides of polyketide origin with antibacterial activities. Their biosynthesis has been proposed to utilize succinate as a building block. However, the mechanism of succinate incorporation into a polyketide was unclear. Here, we report identification of a pamamycin biosynthesis gene cluster by aligning genomes of two pamamycin‐producing strains. This unique cluster contains polyketide synthase (PKS) genes encoding seven discrete ketosynthase (KS) enzymes and one acyl‐carrier protein (ACP)‐encoding gene. A cosmid containing the entire set of genes required for pamamycin biosynthesis was successfully expressed in a heterologous host. Genetic and biochemical studies allowed complete delineation of pamamycin biosynthesis. The pathway proceeds through 3‐oxoadipyl‐CoA, a key intermediate in the primary metabolism of the degradation of aromatic compounds. 3‐Oxoadipyl‐CoA could be used as an extender unit in polyketide assembly to facilitate the incorporation of succinate.     

Out of the blue: semiconductor laser pumped visible rare‐earth doped lasers

The rise of semiconductor‐based pump sources such as In_xGa_1‐xN‐laser diodes or frequency‐doubled optically pumped semiconductor lasers with emission wavelengths in the blue encourages a revisitation of the rare‐earth ions Pr³⁺, Sm³⁺, Tb³⁺, Dy³⁺, Ho³⁺ and Er³⁺ with respect to their properties as active ions in crystalline solid‐state laser materials with direct emission in the visible spectral range. Nowadays, some of these blue‐pumped visible lasers compete with Nd³⁺‐lasers in terms of efficiency and direct lasing at various colors from the cyan‐blue to the deep red can be addressed in very simple and compact laser setups. This paper highlights the spectroscopic properties of suitable rare‐earth ions for visible lasing and reviews the latest progress in the field of blue‐pumped visible rare‐earth doped solid‐state lasers.

     

Total synthesis of pamamycin-649B

The first total synthesis of the macrodiolide antibiotic pamamycin-649B (1) was achieved by using sultone methodology. The diethyl substituted larger hydroxy acid fragment was constructed in a concise fashion through domino elimination/alkoxide-directed 1,6-additions of ethyllithium to sultones derived from intramolecular Diels-Alder reaction of furan-containing vinylsulfonates. Intermolecular Yamaguchi esterification of the two hydroxy acid building blocks and subsequent Yamaguchi cyclization eventually provided the target macrocycle 1. Since the final lactonization with formation of the ester linkage between C1' and the C8 oxygen proceeded with complete C2' epimerization, the more readily available C2' epimeric smaller fragment could be used to streamline the synthetic sequence.     

Electronic and vibrational spectroscopy of intermediates in methane-to-methanol conversion by CoO+

At room temperature, cobalt oxide cations directly convert methane to methanol with high selectivity but very low efficiency. Two potential intermediates of this reaction, the [HO-Co-CH(3)](+) insertion intermediate and [H(2)O-Co=CH(2)](+) aquo-carbene complex are produced in a laser ablation source and characterized by electronic and vibrational spectroscopy. Reaction of laser-ablated cobalt cations with different organic precursors seeded in a carrier gas produces the intermediates, which subsequently expand into vacuum and cool. Ions are extracted into a time-of-flight mass spectrometer and spectra are measured via photofragment spectroscopy. Photodissociation of [HO-Co-CH(3)](+) in the visible and via infrared multiple photon dissociation (IRMPD) makes only Co(+) + CH(3)OH, while photodissociation of [H(2)O-Co=CH(2)](+) produces CoCH(2)(+) + H(2)O. The electronic spectrum of [HO-Co-CH(3)](+) shows progressions in the excited state Co-C stretch (335 cm(-1)) and O-Co-C bend (90 cm(-1)); the IRMPD spectrum gives ν(OH) = 3630 cm(-1). The [HO-Co-CH(3)](+)(Ar) complex has been synthesized and its vibrational spectrum measured in the O-H stretching region. The resulting spectrum is sharper than that obtained via IRMPD and gives ν(OH) = 3642 cm(-1). Also, an improved potential energy surface for the reaction of CoO(+) with methane has been developed using single point energies calculated by the CBS-QB3 method for reactants, intermediates, transition states and products.     

Metal π-complexes of benzene derivatives. Part. 38. Pentaphenyltriphosphane(5) as a chelating η12-ligand. Unusual formation of an interannular –(PPh)3–bridge at bis(benzene)chromium

[(l-6):(1′-6′)-η-Pentaphenyltriphosphane(5)]chromium ( 8 ), which is formed from bis(lithio-η⁶-benzene)-chromium and dichlorophenylphosphane, and which is prepared more rationally from bis(chloro-η⁶-benzene)-chromium and K₂P₃Ph₃, is the first sandwich complex featuring an interannular oligophosphane bridge –(PPh)_n-, n ≥ 2; ³¹P{¹H}- and ¹H-NMR spectra suggest that the stereoisomer 8 -meso₁ is formed exclusively and that the –(PPh)₃- link in this triphospha[3]chromocyclophane is non-fluxional in the range 193 < T < 348 K.