Step-Economic Total Synthesis of Melosatin A from Eugenol.

An efficient and straightforward route toward the isatin-type natural product melosatin A is reported, employing a trisubstituted aniline as a key intermediate. The latter was synthesized in 4 steps and 60% overall yield from eugenol, through its regioselective nitration, sequentially followed by a Williamson methylation, an olefin cross-metathesis with 4-phenyl-1-butene and the simultaneous reduction of olefin and nitro groups. The final step, a Martinet cyclocondensation of the key aniline with diethyl 2-ketomalonate, provided the natural product with 68% yield.

Changes in Oxygen Saturation During Fiberoptic Bronchoscopy: High-Flow Nasal Cannula versus Standard Oxygen Therapy.

BACKGROUND: Hypoxemia is a relatively common complication in stable patients during fiberoptic bronchoscopy (FOB). To prevent this complication, high-flow nasal cannula (HFNC) has been described as an alternative to standard oxygen therapy. However, the advantages of HFNC over standard oxygen therapy in acute care patients receiving supplemental oxygen before FOB performed with an oral approach are unknown. METHODS: We conducted an observational study that involved subjects with a presumptive diagnosis of pneumonia and a clinical indication for a bronchial aspirate sample. The type of oxygen support (standard oxygen therapy vs HFNC) was selected according to availability. The oxygen flow in the HFNC group was 60 L/min. In both groups, the FIO2 was set at 0.40. Hemodynamic, respiratory dynamics, and gas exchange data were collected at baseline, before, during, and 24 h after FOB. RESULTS: Forty subjects were included, 20 in each group (HFNC and standard oxygen therapy). The study was performed on day 5 of hospitalization in the HFNC group and on day 4 in the standard oxygen therapy group (P = .10). No significant between-group differences in baseline characteristics were observed. HFNC vs standard oxygen therapy was associated with a smaller decrease in SpO2 levels during the procedure (94% vs 90%; P = .040, respectively) and with less variation between the last SpO2 measured before FOB and the lowest SpO2 during FOB (Δ SpO2 ): 2% versus 4.5% (P = .01, respectively). CONCLUSIONS: In acute subjects who required oxygen support before FOB, the use of HFNC during FOB with an oral approach was associated with a smaller decrease in SpO2 and lower Δ SpO2 compared with standard oxygen therapy.

Functional modeling of the MnCAT active site with a dimanganese(III) complex of an unsymmetrical polydentate N3O3 ligand.

A new diMnIII complex, [Mn2L(OAc)2(H2O)](BPh4)·3H2O (1), obtained with the unsymmetrical N3O3-ligand H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(benzyl)amino]propan-2-ol, has been prepared and characterized. The unsymmetrical hexadentate ligand L3- leads to coordination dissymmetry (dissimilar donor atoms) around each Mn ion (N2O4 and NO4(solvent), respectively) leaving one labile site on one of the two Mn ions that facilitates interaction of the metal center with H2O2, as in Mn catalase. 1 is able to catalyze H2O2 disproportionation in acetonitrile, with second-order rate constant kcat = 23.9(2) M-1 s-1. The accessibility of the MnII2 state and the closeness of the two one-electron reduction processes suggest 1 employs MnIII2/MnII2 oxidation states for catalysis.

Crystal structure of cis-1-phenyl-8-(pyridin-2-ylmeth-yl)dibenzo[1,2-c:2,1-h]-2,14-dioxa-8-aza-1-borabi-cyclo-[4.4.0]deca-3,8-diene.

The title compound, C26H23BN2O2, was obtained as by product during synthetic attempts of a complexation reaction between the tripodal ligand H2L [N,N-bis-(2-hy-droxy-benz-yl)(pyridin-2-yl)methyl-amine] and manganese(III) acetate in the presence of NaBPh4. The isolated B-phenyl dioxaza-borocine contains an N→B dative bond with a cis conformation. In the crystal, C-H⋯O hydrogen bonds define chains parallel to the b-axis direction. A comparative analysis with other structurally related derivatives is also included, together with a rationalization of the unexpected production of this zwitterionic heterocycle.

Localized Subcarinal Adenitis following Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure for the diagnosis of mediastinal lymph nodes and masses. Its complications are rare and include hemorrhage, pneumothorax and infections such as mediastinitis. We report the case of a 51-year-old patient who presented with a localized subcarinal adenitis after EBUS-TBNA. Germs colonizing the oropharynx may have been dragged along by the echobronchoscope, inoculating the punctured mediastinal lymph node.

A new mononuclear manganese(III) complex of an unsymmetrical hexadentate N3O3 ligand exhibiting superoxide dismutase and catalase-like activity: synthesis, characterization, properties and kinetics studies.

A mononuclear Mn(III) complex MnL·4H2O (H3L=1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(4-methylbenzyl)amino]propan-2-ol) has been prepared and characterized. This complex catalyzes the dismutation of superoxide efficiently, with catalytic rate constant kcat=1.7×10(6)M(-1)s(-1) and IC50 1.26µM, obtained through the nitro blue tetrazolium photoreduction inhibition superoxide dismutase assay, in aqueous solution of pH7.8. MnL is also able to disproportionate more than 300 equivalents of H2O2 in CH3CN, with initial rate of H2O2 decomposition given by ri=kcat [MnL](2) [H2O2] and kcat=1.32(2)mM(-2)min(-1). The accessibility of the Mn(IV) state (E(p)=0.53V vs. saturated calomel electrode), suggests MnL employs a high-valent catalytic cycle to decompose O2(-) and H2O2.

Trinuclear manganese complexes of unsymmetrical polypodal diamino N3O3 ligands with an unusual [Mn3(µ-OR)4]5+ triangular core: synthesis, characterization, and catalase activity.

Two new tri-Mn(III) complexes of general formula [Mn3L2(µ-OH)(OAc)]ClO4 (H3L = 1-[N-(2-pyridylmethyl),N-(2-hydroxybenzyl)amino]-3-[N'-(2-hydroxybenzyl),N'-(4-X-benzyl)amino]propan-2-ol; 1ClO4, X = Me; 2ClO4, X = H) have been prepared and characterized. X-ray diffraction analysis of 1ClO4 reveals that the complex cation possesses a Mn3(µ-alkoxo)2(µ-hydroxo)(µ-phenoxo)(4+) core, with the three Mn atoms bound to two fully deprotonated N3O3 chelating L(3-), one exogenous acetato ligand, and one hydroxo bridge, the structure of which is retained upon dissolution in acetonitrile or methanol. The three Mn atoms occupy the vertices of a nearly isosceles triangle (Mn1···Mn3 = 3.6374(12) Å, Mn2···Mn3 3.5583(13) Å, and Mn1···Mn2 3.2400(12) Å), with one substitution-labile site on the apical Mn ion occupied by terminally bound monodentate acetate. Temperature-dependent magnetic susceptibility studies indicate the presence of predominant antiferromagnetic intramolecular interactions between Mn(III) ions in 1ClO4. Complexes 1ClO4 and 2ClO4 decompose H2O2 at comparable rates upon initial binding of peroxide through acetate substitution, with retention of core structure during catalysis. Kinetic and spectroscopic studies suggest that these complexes employ the [Mn-(µ-oxo/aquo)-Mn](4+) moiety to activate peroxide, with the additional (µ-alkoxo)(µ-phenoxo)Mn(µ-alkoxo) metallobridge carrying out a structural function.

Alternative ground states enable pathway switching in biological electron transfer.

Electron transfer is the simplest chemical reaction and constitutes the basis of a large variety of biological processes, such as photosynthesis and cellular respiration. Nature has evolved specific proteins and cofactors for these functions. The mechanisms optimizing biological electron transfer have been matter of intense debate, such as the role of the protein milieu between donor and acceptor sites. Here we propose a mechanism regulating long-range electron transfer in proteins. Specifically, we report a spectroscopic, electrochemical, and theoretical study on WT and single-mutant Cu(A) redox centers from Thermus thermophilus, which shows that thermal fluctuations may populate two alternative ground-state electronic wave functions optimized for electron entry and exit, respectively, through two different and nearly perpendicular pathways. These findings suggest a unique role for alternative or "invisible" electronic ground states in directional electron transfer. Moreover, it is shown that this energy gap and, therefore, the equilibrium between ground states can be fine-tuned by minor perturbations, suggesting alternative ways through which protein-protein interactions and membrane potential may optimize and regulate electron-proton energy transduction.

Electronic structure of the ground and excited states of the Cu(A) site by NMR spectroscopy.

The electronic properties of Thermus thermophilus Cu(A) in the oxidized form were studied by (1)H and (13)C NMR spectroscopy. All of the (1)H and (13)C resonances from cysteine and imidazole ligands were observed and assigned in a sequence-specific fashion. The detection of net electron spin density on a peptide moiety is attributed to the presence of a H-bond to a coordinating sulfur atom. This hydrogen bond is conserved in all natural Cu(A) variants and plays an important role for maintaining the electronic structure of the metal site, rendering the two Cys ligands nonequivalent. The anomalous temperature dependence of the chemical shifts is explained by the presence of a low-lying excited state located about 600 cm(-1) above the ground state. The room-temperature shifts can be described as the thermal average of a sigma(u)* ground state and a pi(u) excited state. These results provide a detailed description of the electronic structure of the Cu(A) site at atomic resolution in solution at physiologically relevant temperature.