Regio- and Z-Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro-λ6-Sulfanyl Alkynes under Superbasic,Naked Anion Conditions

Alkyne hydroamination is an effective approach for the production of enamines and enamine-containing N-heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π-system. Herein, we propose a methodology involving β-regio- and Z-selective alkyne hydroamination by using tetrafluoro-λ⁶-sulfanyl (SF₄) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N-heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF₄-linked Z-vinyl enamines with β-regioselectively. Moreover, the method can be extended to the β- and Z-controlled, base-mediated alkyne hydrophenoxylation with phenols to provide SF₄-linked Z-vinyl ethers in high yields. As the SF₄ unit has attracted attention as a bioisostere for alkynes, p-benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF₄-containing molecules.     

A Unique Tryptophan C‐Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway

Cyanobactins are a rapidly growing family of linear and cyclic peptides produced by cyanobacteria. Kawaguchipeptins A and B, two macrocyclic undecapeptides reported earlier from Microcystis aeruginosa NIES‐88, are shown to be products of the cyanobactin biosynthetic pathway. The 9 kb kawaguchipeptin (kgp) gene cluster was identified in a 5.26 Mb draft genome of Microcystis aeruginosa NIES‐88. We verified that this gene cluster is responsible for the production of the kawaguchipeptins through heterologous expression of the kgp gene cluster in Escherichia coli. The KgpF prenyltransferase was overexpressed and was shown to prenylate C‐3 of Trp residues in both linear and cyclic peptides in vitro. Our findings serve to further enhance the structural diversity of cyanobactins to include tryptophan‐prenylated cyclic peptides.     

The dynamical properties of the aromatic hydrogen bond in NH4(C6H5)4B from quasielastic neutron scattering

NH(4)(C(6)H(5))(4)B represents a prototypical system for understanding aromatic H bonds. In NH(4)(C(6)H(5))(4)B an ammonium cation is trapped in an aromatic cage of four phenyl rings and each phenyl ring serves as a hydrogen bond acceptor for the ammonium ion as donor. Here the dynamical properties of the aromatic hydrogen bond in NH(4)(C(6)H(5))(4)B were studied by quasielastic incoherent neutron scattering in a broad temperature range (20< or =T< or =350 K). We show that in the temperature range from 67 to 350 K the ammonium ions perform rotational jumps around C(3) axes. The correlation time for this motion is the lifetime of the "transient" H bonds. It varies from 1.5 ps at T=350 K to 150 ps at T=67 K. The activation energy was found to be 3.14 kJ mol, which means only 1.05 kJ mol per single H bond for reorientations around the C(3) symmetry axis of the ammonium group. This result shows that the ammonium ions have to overcome an exceptionally low barrier to rotate and thereby break their H bonds. In addition, at temperatures above 200 K local diffusive reorientational motions of the phenyl rings, probably caused by interaction with ammonium-group reorientations, were found within the experimental observation time window. At room temperature a reorientation angle of 8.4 degrees +/-2 degrees and a correlation time of 22+/-8 ps were determined for the latter. The aromatic H bonds are extremely short lived due to the low potential barriers allowing for molecular motions with a reorientational character of the donors. The alternating rupture and formation of H bonds causes very strong damping of the librational motion of the acceptors, making the transient H bond appear rather flexible.     

Rotational motion of the water molecules in the superconductor Na0.28CoO$_{\mathsf{2}} \!\cdot \!{\sf y}$H2O

Quasielastic neutron scattering (QENS) has been used to investigate the dynamical behaviour of H₂O in the superconductor Na_0.28CoO₂ .yH₂O. The measurements were obtained at room temperature for a molar concentration of water, y = 1.3. From the analysis of the Q-dependence of the EISF and the line-width we found that the water dynamics can be well described by rotational motion that likely correspond to re-orientation of the H₂O molecule. We were also able to define a rotational correlation time of τ= 1.85 ps.     

Dynamics of Water in NaxCoO2.yH2O

Incoherent inelastic neutron scattering experiments were performed on Na0.7CoO2 and Na0.28CoO2.1.3H2O in order to understand how the dynamics of the hydrogen-bond network of water is modified in the triangular crystalline lattice NaxCoO2.yH2O. Using quasi-elastic neutron scattering (QENS), we were able to differentiate between two types of proton dynamics: a fast process (due to water strongly bound into the sodium cobalt oxyhydrate structure during the hydration process) and a slow process (likely attributable to a collective motion). High-resolution QENS experiments, carried out on Na0.28CoO2.1.3H2O, show that, at temperatures above 310 K, the water dynamics can be well-described by a random jump diffusion model characterized by a diffusion constant equal to 0.9 x 10(-9)m2/s, which is significantly lower than the rate of diffusion for bulk water. Furthermore, our results indicate that, at room temperature, the sodium ions have no influence on the rotational dynamics of the "fast" water molecules.     

Microdrop analysis of a bead-based immunoassay

The progress to electrochemical detection of a microbead-based immunoassay in small volumes has led to a reduced assay time and lower detection limits. Three electrochemical techniques are described for an immunoassay with detection in a microdrop. The techniques are amperometric detection with a rotating disk electrode (RDE), a microelectrode, and an interdigitated array (IDA) electrode. An enzyme-labeled sandwich immunoassay with mouse IgG as the model analyte is used to demonstrate the three techniques. The microbead assay is carried out in a test tube using a magnet to control bead collection. Once the immunocomplex is formed on the microbead, the beads are transferred to a microdrop where the enzyme, either alkaline phosphatase or β-galactosidase, generates 4-aminophenol (PAP). PAP is oxidized at the electrode with an applied potential of +290 mV vs. Ag/AgCl. For all three techniques, the upper limit of the dynamic range was 1000 ng/ml mouse IgG, and the detection limits were: 50 ng/ml for the RDE, 40 ng/ml for the microelectrode, and 26 ng/ml for the IDA electrode.     

Analysis of lipids with desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS) and desorption electrospray ionization-mass spectrometry (DESI-MS)

In this article, the effect of spray solvent on the analysis of selected lipids including fatty acids, fat-soluble vitamins, triacylglycerols, steroids, phospholipids, and sphingolipids has been studied by two different ambient mass spectrometry (MS) methods, desorption electrospray ionization-MS (DESI-MS) and desorption atmospheric pressure photoionization-MS (DAPPI-MS). The ionization of the lipids with DESI and DAPPI was strongly dependent on the spray solvent. In most cases, the lipids were detected as protonated or deprotonated molecules; however, other ions were also formed, such as adduct ions (in DESI), [M-H](+) ions (in DESI and DAPPI), radical ions (in DAPPI), and abundant oxidation products (in DESI and DAPPI). DAPPI provided efficient desorption and ionization for neutral and less polar as well as for ionic lipids but caused extensive fragmentation for larger and more labile compounds because of a thermal desorption process. DESI was more suitable for the analysis of the large and labile lipids, but the ionization efficiency for less polar lipids was poor. Both methods were successfully applied to the direct analysis of lipids from pharmaceutical and food products. Although DESI and DAPPI provide efficient analysis of lipids, the multiple and largely unpredictable ionization reactions may set challenges for routine lipid analysis with these methods.