Regioselective [3+3] Cyclization of 1,3‐Bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐Trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones: New and Convenient Synthesis of Functionalized 5‐Alkyl‐3‐(trifluoromethyl)phenols

Functionalized 5‐alkyl‐3‐(trifluoromethyl)phenols were prepared by formal [3+3] cyclization of 1,3‐bis(silyloxy)buta‐1,3‐dienes with 1,1,1‐trifluoro‐4‐(silyloxy)alk‐3‐en‐2‐ones derived from 1,1,1‐trifluoroalkane‐2,4‐diones. The latter were prepared by condensation of the dianion of 1,1,1‐trifluoropentane‐2,4‐dione with alkyl halides.     

Identifying Carbohydrate Ligands of a Norovirus P Particle using a Catch and Release Electrospray Ionization Mass Spectrometry Assay

Noroviruses (NoVs), the major cause of epidemic acute gastroenteritis, recognize human histo-blood group antigens (HBGAs), which are present as free oligosaccharides in bodily fluid or glycolipids and glycoproteins on the surfaces of cells. The subviral P particle formed by the protruding (P) domain of the NoV capsid protein serves as a useful model for the study NoV–HBGA interactions. Here, we demonstrate the application of a catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay for screening carbohydrate libraries against the P particle to rapidly identify NoV ligands and potential inhibitors. Carbohydrate libraries of 50 and 146 compounds, which included 18 and 24 analogs of HBGA receptors, respectively, were screened against the P particle of VA387, a member of the predominant GII.4 NoVs. Deprotonated ions corresponding to the P particle bound to carbohydrates were isolated and subjected to collision-induced dissociation to release the ligands in their deprotonated forms. The released ligands were identified by ion mobility separation followed by mass analysis. All 13 and 16 HBGA ligands with intrinsic affinities >500 M^–1 were identified in the 50 and the 146 compound libraries, respectively. Furthermore, screening revealed interactions with a series of oligosaccharides with structures found in the cell wall of mycobacteria and human milk. The affinities of these newly discovered ligands are comparable to those of the HBGA receptors, as estimated from the relative abundance of released ligand ions.      

Hydration of gas-phase ions formed by electrospray ionization

The hydration of gas-phase ions produced by electrospray ionization was investigated. Evidence that the hydrated ions are formed by two mechanisms is presented. First, solvent condensation during the expansion inside the electrospray source clearly occurs. Second, some solvent evaporation from more extensively solvated ions or droplets is apparent. To the extent that these highly solvated ions have solution-phase structures, then the final isolated gas-phase structure of the ion will be determined by the solvent evaporation process. This process was investigated for hydrated gramicidin S in a Fourier-transform mass spectrometer. Unimolecular dissociation rate constants of isolated gramicidin S ions with between 2 and 14 associated water molecules were measured. These rate constants increased from 16 to 230 s-1 with increasing hydration, with smaller values corresponding to magic numbers.     

Activation energies for dissociation of double strand oligonucleotide anions: evidence for watson-crick base pairing in vacuo

The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)(2) (3-), (CCGG)(2) (3-), (AATTAAT)(2) (3-), (CCGGCCG)(2) (3-), A(7).T(7) (3-), A(7).A(7) (3-), T(7).T(7) (3-), and A(7).C(7) (3-) were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 10(13) to 10(19) s(-1). Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a - base) and w ions. Four pieces of evidence are presented which indicate that Watson-Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A(7).T(7) (3-), to the single strands is significantly higher than that for the related noncomplementary A(7).A(7) (3-) and T(7).T(7) (3-) dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A(7).A(7) (3-) and A(7).C(7) (3-) but not for A(7).T(7) (3-) consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (-DeltaH(d)) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A(7).T(7) (3-) duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent.     

Detecting Protein–Glycolipid Interactions Using CaR-ESI-MS and Model Membranes: Comparison of Pre-loaded and Passively Loaded Picodiscs

Catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS), implemented using model membranes (MMs), is a promising approach for the discovery of glycolipid ligands of glycan-binding proteins (GBPs). Picodiscs (PDs), which are lipid-transporting complexes composed of the human sphingolipid activator protein saposin A and phospholipids, have proven to be useful MMs for such studies. The present work compares the use of conventional (pre-loaded) PDs with passively loaded PDs (^PLPDs) for CaR-ESI-MS screening of glycolipids against cholera toxin B subunit homopentamer (CTB₅). The pre-loaded PDs were prepared from a mixture of purified glycolipid and phospholipid or a mixture of lipids extracted from tissue, while the ^PLPDs were prepared by incubating PDs containing only phospholipid with glycolipid-containing lipid mixtures in aqueous solution. Time-dependent changes in the composition of the ^PLPDs produced by incubation with glycomicelles of the ganglioside GM1 were monitored using collision-induced dissociation of the gaseous PD ions and from the extent of ganglioside binding to CTB₅ measured by ESI-MS. GM1 incorporation into PDs was evident within a few hours of incubation. At incubation times ≥ 10 days, GM1 binding to CTB₅ was indistinguishable from that observed with pre-loaded PDs produced directly from GM1 at the same concentration. Comparison of ganglioside binding to CTB₅ measured for pre-loaded PDs and ^PLPDs prepared from glycolipids extracted from pig and mouse brain revealed that the ^PLPDs allow for the detection of a greater number of ganglioside ligands. Together, the results of this study suggest ^PLPDs may have advantages over conventionally prepared PDs for screening glycolipids against GBPs using CaR-ESI-MS.

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Interpretation of harmonic structure in solar type II radio bursts

Spectrographic and partly imaging observations of three Type II solar radio bursts displaying three drifting bands with frequencies related as 1?2?3 are discussed. The radio data of two of these events were simultaneousely recorded by the digital radiospectrograph of the Observatory of Solar Radioastronomy in Potsdam-Tremsdorf and the radioheliograph of the Paris-Meudon Observatory in Nan?ay. The data allow the brightness temperatures of radio emission in the three frequency bands to be determined. The second harmonic is traditionally explained as a result of coalescence of two plasma waves into an electromagnetic wave at twice the plasma frequency. Two nonlinear merging processes—the coalescence of three plasma waves, and of a plasma wave and an electromagnetic wave at twice the plasma frequency—are considered to explain the occurrence of the third harmonic on Type II dynamic spectra. The analysis shows that both processes can fit the observed brightness temperatures of the second and third harmonic. The first process acts preferably at low phase velocities of plasma waves and sharp electron density gradients in the source, and the second process dominates in the case of high plasma wave phase velocities. It is shown that the occurrence of the third harmonic in type II bursts due to nonlinear processes in the coronal plasma indicates not only a powerful event but also some specific conditions in the shock or foreshock region. Finally, we propose a method to distinguish between the two invoked nonlinear processes by a statistical investigation of Type II burst data. Institute of Applied Physics, Russian Academy of Sciences, Nizhny Novgorod, Russia; Astrophysical Institute, Potsdam, Germany; Paris-Meudon Observatory, France. Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Radiofizika, Vol. 41, No. 1, pp. 61–83, January, 1998.     

Chemical and microstructural study of the oxygen passivation behaviour of nanocrystalline Mg and MgH2

Nanocrystalline Mg and MgH₂ samples have been prepared by high-energy ball milling and gas phase condensation methods. Starting from these materials in their “as received” state without air exposure, a study of the oxygen and air passivation behaviour was carried out by “in situ” analysis of the samples by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The binding energy and photoemission Auger parameters have been determined for metallic magnesium as well as for magnesium hydride, oxide and hydroxide species. Values of the MgH₂ material were reported for the first time. The study clearly shows the formation of an oxide passivation layer of ca. 3-4 nm in thickness for all the nanocrystalline magnesium samples handled under controlled inert gas atmospheres. A hydroxide like amorphous layer is formed at the topmost surface layers of the nanocrystalline Mg and MgH₂ samples. The implication of these studies for H₂ storage and transport applications of nanocrystalline magnesium is discussed.