Stepwise delivery of two methoxy groups of arylaldehyde acetals across the phenyl ring. Vacant site-controlled palladium catalysis

A new catalytic cyclization of o-alkynylbenzaldehyde acetals 1 to the functionalized indenes 2 was found to be strictly controlled by the number of triphenylphosphine ligands on the Pd catalyst. Only complexes with three available coordination sites on Pd catalyze this reaction. Mechanistic study suggests that pi-coordination of Pd to the benzene ring is a key step controlled by the number of vacant coordination sites.     

Calculation of diatomic van der Waals systems inert gas Atom-Halogen type inert gas ion in the ground state

Interatomic potentials are calculated for the systems inert gas ion in the ground state-inert gas atom Ne⁺, Xe⁺ -Ne, Ar, Kr, Xe, Fr. The calculation is performed by the effective pseudopotential method using the new form of the polarization interaction potential obtained by calculating the most important polarization diagrams of perturbation theory in the Thomas-Fermi approximation. The quasimolecular states of these van der Waals systems are calculated to refine the available data; some data are obtained for the first time. Translated fromZhumal Strukturnoi Khimii, Vol. 39, No. 4, pp. 591–595, July–August, 1998.     

High-resolution electron spin resonance spectroscopy of XeF* in solid argon. The hyperfine structure constants as a probe of relativistic effects in the chemical bonding properties of a heavy noble gas atom

Xenon fluoride radicals were generated by solid-state chemical reactions of mobile fluorine atoms with xenon atoms trapped in Ar matrix. Highly resolved electron spin resonance spectra of XeF* were obtained in the temperature range of 5-25 K and the anisotropic hyperfine parameters were determined for magnetic nuclei 19F, 129Xe, and 131Xe using naturally occurring and isotopically enriched xenon. Signs of parallel and perpendicular hyperfine components were established from analysis of temperature changes in the spectra and from numerical solutions of the spin Hamiltonian for two nonequivalent magnetic nuclei. Thus, the complete set of components of hyperfine- and g-factor tensors of XeF* were obtained: 19F (Aiso=435, Adip=1249 MHz) and 129Xe (Aiso=-1340, Adip=-485 MHz); g(parallel)=1.9822 and g(perpendicular)=2.0570. Comparison of the measured hyperfine parameters with those predicted by density-functional theory (DFT) calculations indicates, that relativistic DFT gives true electron spin distribution in the 2Sigma+ ground-state, whereas nonrelativistic theory underestimates dramatically the electron-nuclear contact Fermi interaction (Aiso) on the Xe atom. Analysis of the obtained magnetic-dipole interaction constants (Adip) shows that fluorine 2p and xenon 5p atomic orbitals make a major contribution to the spin density distribution in XeF*. Both relativistic and nonrelativistic calculations give close magnetic-dipole interaction constants, which are in agreement with the measured values. The other relativistic feature is considerable anisotropy of g-tensor, which results from spin-orbit interaction. The orbital contribution appears due to mixing of the ionic 2Pi states with the 2Sigma+ ground state, and the spin-orbit interaction plays a significant role in the chemical bonding of XeF*.     

Synthesis of new tropinone derivatives by palladium-catalyzed couplings of 8-azabicyclo[3.2.1]oct-2-enyl nonaflates

Whereas tropinone derived nonaflate 3 was no suitable precursor for Heck-reactions, the related carbamate 7 was an excellent substrate for palladium-catalyzed processes. Nonaflate 7 was either isolated in excellent yield by LDA treatment of ketone 5 followed by trapping with NfF (nonafluorobutanesulfonyl fluoride) or generated in situ by fluoride-catalyzed reaction of silyl enol ether 6 with NfF. The desired 1,3-diene 8 was prepared by conventional Heck-reaction of nonaflate 7 with methyl acrylate in almost quantitative yield. Alternatively, the one-pot nonaflation-Heck protocol starting from silyl enol ether 6 provided 8 in good yield. The couplings of acrylonitrile or phenyl vinyl sulfone were also performed with in situ generated 7 and they afforded the expected 1,3-dienes 9 and 10 in good yields. The Sonogashira-reaction with phenylacetylene also started from silyl enol ether 6 and provided enyne 11 via 7 in good yield. A Diels-Alder reaction of 1,3-diene 8 with N-phenyl maleimide at 100 °C furnished tetracyclic adduct 12 in good yield, with excellent diastereofacial selectivity, but with low endo-exo-selectivity. Nonaflate 14 was easily obtained from the corresponding unsaturated bicyclic ketone 13. It behaved differently in an attempted Heck-reaction and mainly led to fragmentation products 15 and 16, whereas the expected 1,3-diene 17 was formed only as minor component. However, 14 could successfully be used in a Sonogashira-reaction with phenylacetylene to afford compound 18. These transformations demonstrate the great potential of tropinone derived alkenyl nonaflates for diversity oriented syntheses of interesting compounds containing an 8-azabicyclo[3.2.1]octane scaffold.     

Structural characterization of a lanthanum bistriflimide complex, La(N(SO2CF3)2)3(H2O)3, and an investigation of La, Sm, and Eu electrochemistry in a room-temperature ionic liquid, [Me3N(n)Bu][N(SO2CF3)2

The reduction of selected lanthanide cations to the zerovalent state in the room-temperature ionic liquid [Me3N(n)Bu][TFSI] is reported (where TFSI = bistriflimide, [N(SO2CF3)2]-). The lanthanide cations were introduced to the melt as the TFSI hydrate complexes [Ln(TFSI)3(H2O)3] (where Ln = La(III), Sm(III) or Eu(III)). The lanthanum compound [La(TFSI)3(H2O)3] has been crystallographically characterized, revealing the first structurally characterized f-element TFSI complex. The lanthanide in all three complexes was shown to be reducible to the metallic state in [Me3N(n)Bu][TFSI]. For both the Eu and Sm complexes, reduction to the metallic state was achieved via divalent species, and there was an additional observation of the electrodeposition of Eu metal.     

Designed helical peptides inhibit an intramembrane protease

gamma-Secretase cleaves the transmembrane domain of the amyloid precursor protein, a process implicated in the pathogenesis of Alzheimer's disease, and this enzyme is a founding member of an emerging class of intramembrane proteases. Modeling and mutagenesis suggest a helical conformation for the substrate transmembrane domain upon initial interaction with the protease. Moreover, biochemical evidence supports the presence of an initial docking site for substrate on gamma-secretase that is distinct from the active site, a property predicted to be generally true of intramembrane proteases. Here we show that short peptides designed to adopt a helical conformation in solution are inhibitors of gamma-secretase in both cells and enzyme preparations. Helical peptides with all d-amino acids are the most potent inhibitors and represent potential therapeutic leads. Subtle modifications that disrupt helicity also substantially reduce potency, suggesting that this conformation is critical for effective inhibition. Fluorescence lifetime imaging in intact cells demonstrates that helical peptides disrupt binding between substrate and protease, whereas an active site-directed inhibitor does not. These findings are consistent with helical peptides interacting with the initial substrate docking site of gamma-secretase, suggesting a general strategy for the development of potent and specific inhibitors of intramembrane proteases.     

Nucleophilic substitution reactions in tetranitrodibenzo-18-crown-6

The nature of the reaction of a reagent with tetranitrodibenzo-18-crown-6 was found to depend on its basicity. This behavior was interpreted in the framework of the theory of hard and soft acids and bases.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 605–608, May, 1992.     

Structural elucidation of metabolites of ritonavir and indinavir by liquid chromatography-mass spectrometry

The structural elucidation of metabolites of ritonavir and indinavir, HIV-protease inhibitor drugs, by liquid chromatography-electrospray ionization mass spectrometry is described. Ritonavir and indinavir were biotransformed separately by incubation with transplant quality human liver microsomes. The incubation mixture was then analyzed by HPLC coupled to ion trap (ITMS) and triple quadrupole mass analyzers. The metabolites retained most of the structural features of the parent molecules. Baseline chromatographic resolution of isobaric species by gradient elution HPLC permitted rapid structural identification of these metabolites. Both drugs were biotransformed primarily by oxidative and hydrolytic pathways to numerous metabolites that retained many of the features of the parent molecules. Triple quadrupole and ion trap mass spectrometry were applied jointly to thoroughly detect and thoroughly characterize these metabolites. Furthermore, retention-time and data-dependent scanning assured acquisition of detailed MS-MS spectra for rapid detection of metabolic pathways of ritonavir and indinavir. Comparison of the ITMS and triple quadrupole data showed qualitative and quantitative differences in the mass spectral patterns, suggesting that these instruments should be used in parallel to ensure comprehensive metabolite detection and characterization by LC-MS.     

NMR studies of solid state—solvent and H/D isotope effects on hydrogen bond geometries of 1:1 complexes of collidine with carboxylic acids

¹H and ¹⁵N NMR spectra of 10 complexes exhibiting strong OHN hydrogen bonds formed by ¹⁵N-labeled collidine and different proton donors, partially deuterated in mobile proton sites, have been observed by low-temperature NMR spectroscopy using a low-freezing CDF₃/CDF₂Cl mixture as polar aprotic solvent. The following proton donors have been used: HCl, formic acid, acetic acid, various substituted benzoic acids and HBF₄. The slow hydrogen bond exchange regime could be reached below 140 K, which allowed us to resolve ¹⁵N signal splittings due to H/D isotopic substitution. The valence bond order model is used to link the observed NMR parameters to hydrogen bond geometries. The results are compared to those obtained previously [Magn. Reson. Chem. 39 (2001) S18] for the same complexes in the organic solids. The increase of the dielectric constant from the organic solids to the solution (30 at 130 K) leads to a change of the hydrogen bond geometries along the geometric correlation line towards the zwitterionic structures, where the proton is partially transferred from oxygen to nitrogen. Whereas the changes of spectroscopic and, hence, geometric parameters are small for the systems which are already zwitterionic in the solid state, large changes are observed for molecular complexes which exhibit almost a full proton transfer from oxygen to nitrogen in the polar liquid solvent.