Mycopyranone: A 8,8ˈ-binaphthopyranone with potent anti-MRSA activity from the fungus Phialemoniopsis sp.

A new 8,8?-binaphthopyranone (mycopyranone, 1) was isolated from a solid fermentation of Phialemoniopsis sp. (fungal strain MSX61662), and the structure was elucidated via analysis of the NMR and HRESIMS data. The axial chirality of 1 was determined to be M by ECD. The central chirality at C-4/C-4? was assigned through a modified Mosher’s method, while the absolute configuration at C-3/C-3? was deduced based on analysis of the ³J_H-3-H-4 values and NOESY correlations. Compound 1 was evaluated for its antimicrobial properties against Staphylococcus aureus SA1199 and a clinically relevant methicillin-resistant S. aureus strain (MRSA USA300 LAC strain AH1263). Compound 1 inhibited the growth of both strains in a concentration dependent manner with IC₅₀ values in the low μM range. Molecular docking indicated that compound 1 binds to the FtsZ (tubulin-like) protein in the same pocket as viriditoxin (2), suggesting that 1 targets bacterial cell division.     

Calculations of electron inelastic mean free paths. XII. Data for 42 inorganic compounds over the 50 eV to 200 keV range with the full Penn algorithm

We have calculated inelastic mean free paths (IMFPs) for 42 inorganic compounds (AgBr, AgCl, AgI, Al₂O₃, AlAs, AlN, AlSb, cubic BN, hexagonal BN, CdS, CdSe, CdTe, GaAs, GaN, GaP, GaSb, GaSe, InAs, InP, InSb, KBr, KCl, MgF₂, MgO, NaCl, NbC_0.712, NbC_0.844, NbC_0.93, PbS, PbSe, PbTe, SiC, SiO₂, SnTe, TiC_0.7, TiC_0.95, VC_0.76, VC_0.86, Y₃Al₅O₁₂, ZnS, ZnSe, and ZnTe) for electron energies from 50 eV to 200 keV. These calculations were made with energy-loss functions (ELFs) obtained from measured optical constants for 15 compounds while calculated ELFs were utilized for the other 27 compounds. Checks based on ELF sum rules showed that the calculated ELFs were superior to the measured ELFs that we had used previously. Our calculated IMFPs could be fitted to a modified form of the relativistic Bethe equation for inelastic scattering of electrons in matter for energies from 50 eV to 200 keV. The average root-mean-square (RMS) deviation in these fits was 0.60%. The IMFPs were also compared with a relativistic version of our predictive Tanuma-Powell-Penn (TPP-2M) equation. The average RMS deviation in these comparisons was 10.7% for energies between 50 eV and 200 keV. This average RMS deviation is almost the same as that found in a similar comparison for a group of 41 elemental solids (11.9%) although relatively large deviations were found for cubic BN (65.6%) and hexagonal BN (34.3%). If these two compounds are excluded in the comparisons, the average RMS deviation becomes 8.7%. We found generally satisfactory agreement between our calculated IMFPs and values from other calculations and from experiments.     

Controlled transport and focusing of laser-accelerated protons with miniature magnetic devices

This Letter demonstrates the transporting and focusing of laser-accelerated 14 MeV protons by permanent magnet miniature quadrupole lenses providing field gradients of up to 500 T/m. The approach is highly reproducible and predictable, leading to a focal spot of (286 x 173) microm full width at half maximum 50 cm behind the source. It decouples the relativistic laser-proton acceleration from the beam transport, paving the way to optimize both separately. The collimation and the subsequent energy selection obtained are perfectly applicable for upcoming high-energy, high-repetition rate laser systems.     

Allylic alkylation and ring-closing metathesis in sequence: a successful cohabitation of Pd and Ru

An allylic alkylation/ring-closing metathesis domino catalytic process, wherein a palladium and a ruthenium catalyst are concomitantly present in the reaction mixture from the outset of the reaction, is developed. Evidence for Grubbs' catalysts activity in allylic alkylation is also reported.     

Effect of (5'S)-5',8-cyclo-2'-deoxyadenosine on the conformation of di and trinucleotides. A NMR and DFT study

5',8-Purine cyclonucleosides constitute an important class of oxidatively generated tandem lesions whose formation involves initial hydroxyl radical-mediated hydrogen atom abstraction from the 5-hydroxymethyl group of 2-deoxyribose followed by intramolecular cyclization. The present study deals with the synthesis of the 5'S diastereomer of 5',8-cyclo-2'-deoxyadenosine containing di- and tri-oligodeoxynucleotides as an attempt to delineate the conformational changes induced in the DNA fragments by the presence of a rigid modified nucleoside. For this purpose, extensive 1D and 2D NMR measurements that were completed by DFT theoretical calculations were performed. As a striking result, it was found that the covalent bond between C(5') and C(8) in the investigated purine cyclonucleoside induces an unusual West ((0)T(1)) conformation of the furanose ring. Thus it can be postulated that the rigid structure of the tandem lesion would strongly perturb the global geometry of oligonucleotides at the site of the modification and therefore affect the enzymatic activity of DNA polymerases and repair enzymes.     

Modification of membrane heterogeneity by antipsychotic drugs: an X-ray diffraction comparative study

Lipid mixtures are used to mimic biological membranes as they allow characterization of lipid lateral domains defined by their specific lipid molecular organization. Therapeutic agents such as antipsychotic drugs (AP) that may interact with lipids arrangement are likely to modify membrane biological properties. The present study describes the effect of 2 typical and 5 atypical antipsychotic drugs on an aqueous co-dispersion of a lipid mixture made of egg phosphatidylcholine (PC)/brain sphingomyelin (SM)/cholesterol (1/1/1 mol/mol/mol). Lamellar liquid-ordered (Lo) and liquid-disordered (Ld) phase coexistence was identified in the control and antipsychotic-added mixtures at 37 degrees C using synchrotron small-angle X-ray scattering methods (XRD). Intensity of the Bragg peaks was used to generate electron density profiles (EDP) allowing bilayer thickness calculation. All antipsychotic except from amisulpride induced a Lo phase bilayer thickness (d(pp)) decrease. Chlorpromazine, haloperidol, amisulpride and 9-0H-risperidone induced a Ld d(pp) increase while ziprazidone, risperidone and clozapine induced a Ld d(pp) decrease, indicating that antipsychotic atypicality is not associated with a specific d(pp) modification on our lipid model mixture. Results are discussed in terms of competition of antipsychotic compounds with cholesterol and mode of reorganization of lateral domains. A pharmacological relevance of these changes is also discussed.     

Synthesis, characterization, and DFT/TD-DFT calculations of highly phosphorescent blue light-emitting anionic iridium complexes

Highly phosphorescent blue-light-emitting anionic iridium complexes (C4H9)4N[Ir(2-phenylpyridine)2(CN)2] (1), (C4H9)4N[Ir(2-phenyl-4-dimethylaminopyridine)2(CN)2] (2), (C4H9)4N[Ir(2-(2,4-difluorophenyl)-pyridine)2(CN)2] (3), (C4H9)4N[Ir(2-(2,4-difluorophenyl)-4-dimethylaminopyridine)2(CN)2] (4), and (C4H9)4N[Ir(2-(3,5-difluorophenyl)-4-dimethylaminopyridine)2(CN)2] (5) were synthesized and characterized using NMR, UV-vis absorption, and emission spectroscopy and electrochemical methods. In these complexes color and quantum yield tuning aspects are demonstrated by modulating the ligands with substituting donor and acceptor groups on both the pyridine and phenyl moieties of 2-phenylpyridine. Complexes 1-5 display intense photoluminescence maxima in the blue region of the visible spectrum and exhibit very high phosphorescence quantum yields, in the range of 50-80%, with excited-state lifetimes of 1-4 micros in acetonitrile solution at 298 K. DFT and time dependent-DFT calculations were performed on the ground and excited states of the investigated complexes to provide insight into the structural, electronic, and optical properties of these systems.