Infrared-infrared double resonance spectroscopy of the isomers of acetylene-HCN and cyanoacetylene-HCN in helium nanodroplets

Infrared-infrared double resonance spectroscopy is used to probe the vibrational dynamics of molecular complexes solvated in helium nanodroplets. We report results for the acetylene-HCN and cyanoacetylene-HCN binary complexes, each having two stable isomers. We find that vibrational excitation of an acetylene-HCN complex results in a population transfer to the other isomer. Photoinduced isomerization is found to be dependent on both the initially excited vibrational mode and the identity of the acetylene-HCN isomer. However, population transfer is not observed for the cyanoacetylene-HCN complexes. The results are rationalized in terms of the ab initio intermolecular potential energy surfaces for the two systems with particular emphasis on the long-range barriers to rearrangement.     

Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: asymmetric glycolate aldol reactions and biological evaluation

The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10:1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.     

Highly enantioselective copper-bisoxazoline-catalyzed allylic oxidation of cyclic olefins with tert-butyl p-nitroperbenzoate

Catalytic asymmetric allylic oxidation of cyclic olefins ocurrs for the first time in very high (94-99% ee) enantioselectivity using copper(I) complexes of malonyl derived bisoxazolines and tert-butyl p-nitroperbenzoate giving allyl benzoates in moderate yield. The copper complex, 15 mol %, was used in acetonitrile at -20 degrees C over an extended period, 5-12 d, with excess olefin together with one equivalent of perester. The S-esters were generated in accord with the model proposed previously for the (S,S)-bisoxazoline ligand. An eta2 intermediate was ruled out using low-temperature 13C NMR with the complex in the presence of olefin.     

Impact of Gd3+ on DNP of [1-13C]pyruvate doped with trityl OX063, BDPA, or 4-oxo-TEMPO

Hyperpolarized [1-(13)C]pyruvate has become an important diagnostic tracer of normal and aberrant cellular metabolism for in vitro and in vivo NMR spectroscopy (MRS) and imaging (MRI). In pursuit of achieving high NMR signal enhancements in dynamic nuclear polarization (DNP) experiments, we have performed an extensive investigation of the influence of Gd(3+) doping, a parameter previously reported to improve hyperpolarized NMR signals, on the DNP of this compound. [1-(13)C]Pyruvate samples were doped with varying amounts of Gd(3+) and fixed optimal concentrations of free radical polarizing agents commonly used in fast dissolution DNP: trityl OX063 (15 mM), 4-oxo-TEMPO (40 mM), and BDPA (40 mM). In general, we have observed three regions of interest, namely, (i) a monotonic increase in DNP-enhanced nuclear polarization P(dnp) upon increasing the Gd(3+) concentration until a certain threshold concentration c(1) (1-2 mM) is reached, (ii) a region of roughly constant maximum P(dnp) from c(1) until a concentration threshold c(2) (4-5 mM), and (iii) a monotonic decrease in P(dnp) at Gd(3+) concentration c > c(2). Of the three free radical polarizing agents used, trityl OX063 gave the best response to Gd(3+) doping, with a 300% increase in the solid-state nuclear polarization, whereas addition of the optimum Gd(3+) concentration on BDPA and 4-oxo-TEMPO-doped samples only yielded a relatively modest 5-20% increase in the base DNP-enhanced polarization. The increase in P(dnp) due to Gd(3+) doping is ascribed to the decrease in the electronic spin-lattice relaxation T(1e) of the free radical electrons, which plays a role in achieving lower spin temperature T(s) of the nuclear Zeeman system. These results are discussed qualitatively in terms of the spin temperature model of DNP.     

Theoretical simulation of backscattered electron images of Si/SixGe1-x structures with a scanning electron microscope

In this work, we report on a theoretical study of the contrast formation at Si/Si_xGe_1–x interfaces in backscattered electron images of a scanning electron microscope. The contrast at the heterointerface is calculated for different atomic concentrations (0 < × < 1) and energies (E₀ = 10 and 20 keV). The electron scattering phenomenon is simulated by employing a Monte Carlo method by using a single scattering approach. The signal intensity close to the interface shows a peak on the alloy side and a dip on the Si side. We explain this phenomenon by using the diffusion theory of the backscattered electrons. The spatial resolution increases by decreasing the Si concentration in the alloy side and by decreasing the beam energy.     

Palladium-imidazolium carbene catalyzed Mizoroki-Heck coupling with aryl diazonium ions

[reaction: see text] Catalyst formed from N,N-bis(2,6-diisopropylphenyl)dihydroimidazolium chloride and palladium(II) acetate (2 mol %) was used, without added base, to efficiently produce Heck coupled products with olefins and aryl diazonium tetrafluoroborate substrates. The reactions were performed at room temperature, giving product in 2-4 h with 80-90% yields for isolated materials. Diazonium ions, formed in situ directly from anilines, also couple under these conditions.     

Solution and crystallographic studies of branched multivalent ligands that inhibit the receptor-binding of cholera toxin

The structure-based design of multivalent ligands offers an attractive strategy toward high affinity protein inhibitors. The spatial arrangement of the receptor-binding sites of cholera toxin, the causative agent of the severe diarrheal disease cholera and a member of the AB(5) bacterial toxin family, provides the opportunity of designing branched multivalent ligands with 5-fold symmetry. Our modular synthesis enabled the construction of a family of complex ligands with five flexible arms each ending with a bivalent ligand. The largest of these ligands has a molecular weight of 10.6 kDa. These ligands are capable of simultaneously binding to two toxin B pentamer molecules with high affinity, thus blocking the receptor-binding process of cholera toxin. A more than million-fold improvement over the monovalent ligand in inhibitory power was achieved with the best branched decavalent ligand. This is better than the improvement observed earlier for the corresponding nonbranched pentavalent ligand. Dynamic light scattering studies demonstrate the formation of concentration-dependent unique 1:1 and 1:2 ligand/toxin complexes in solution with no sign of nonspecific aggregation. This is in complete agreement with a crystal structure of the branched multivalent ligand/toxin B pentamer complex solved at 1.45 A resolution that shows the specific 1:2 ligand/toxin complex formation in the solid state. These results reiterate the power of the structure-based design of multivalent protein ligands as a general strategy for achieving high affinity and potent inhibition.     

Borylation of aryldiazonium ions with N-heterocyclic carbene-palladium catalysts formed without added base

[reaction: see text] A highly efficient catalytic borylation process with aryldiazonium ions was developed using a carbene-palladium catalyst formed in situ to give arylpinacolatoborane products. An X-ray structure for the N-heterocyclic carbene-palladium complex, used as the catalyst formed from bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolium chloride, was obtained without added base.