Planar-chiral cyrhetrenes for the rhodium-catalyzed asymmetric 1,4-addition and the hydrogenation of enamides

[reaction: see text] The syntheses of novel cyrhetrenes 7a-c and 8a,b are described. These planar-chiral, mono- and diphosphines have been applied as ligands in the Rh-catalyzed 1,4-addition reaction to activated olefins and in the Rh-catalyzed hydrogenation of enamide 12, giving the corresponding products with up to 97 and 93% ee, respectively.     

Role of Gold in Inflammation and Tristetraprolin Activity

The zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulating cytokine mRNAs. Misregulation results in arthritis, sepsis and cancer, and there is an interest in modulating TTP activity with exogenous agents. Gold has anti-inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP, suggesting that TTP may be a target of gold. The reactivity of [Au^III(terpy)Cl]Cl₂ with TTP was investigated by UV/Vis spectroscopy, spin-filter inductively coupled plasma mass spectrometry, X-ray absorption spectroscopy and native electrospray ionization mass spectrometry. Au^III was found to replace zinc in the protein active site in the reduced Au^I form, with the Au^I ion coordinated to two cysteine residues in a linear geometry. The replacement of Zn^II with Au^I results in loss of both secondary structure and RNA binding function. In contrast, when Zn^IITTP is bound to its RNA target, no replacement of Zn^II with Au^I is observed, even in the presence of excess Au^IIIterpy. This discovery of differential reactivity of gold with TTP versus TTP/RNA offers a potential strategy for selective targeting with gold complexes to control inflammation.     

Gas-Phase reactions of O 2 −. with alkyl and aryl esters of benzenedicarboxylic acids

The reactions of O ₂ ^?. with alkyl and aryl esters of benzenedicarboxylic acids have been studied under negative-ion chemical ionization (NICI) conditions via a conventional chemical ionization source. Reaction mechanisms have been elucidated by using ion isolation techniques on a Fourier transform ion cyclotron resonance mass spectrometer. In addition, ¹⁸O ₂ ^?. has been used as the reagent and the products of competitive reactions that involve the mixed esters of benzenedicarboxylic acids have been studied. O ₂ ^?. reactions with the alkyl esters of 1,2- and l,3-benzenedicarboxylic acids are attributed to S_N2 displacement at the O-alkyl carbon. The spectra of mixed alkyl esters show that O ₂ ^?. attack is reduced at sterically hindered alkyl groups. In contrast with the spectra of 1,2- and l,3-benzenedicarboxylic acids, the spectra of 1,4-benzenedicarboxylic acids are dominated by M^?. production. Reactions of O ₂ ^?. with phenyl benzoates and the aryl esters of benzenedicarboxylic acids proceed via addition-elimination pathways. Experiments with mixed alkyl-aryl benzenedicarboxylic acid esters show that the addition-elimination reaction pathway is preferred over O-alkyl S_N2 displacement. The O₂/ Ar-NICI mass spectra show features that can be used to distinguish 1,2-, 1,3-, and 1/4-benzenedicarboxylic acid esters. Molecular and fragment ions provide structural information complementary to that generated under electron ionization and chemical ionization conditions.     

Interlaboratory comparison of limits of detectic in negative chemical ionization mass spectrometry

Data are presented on the limits of detection for a series of nine compounds in negative chemical ionization (NCI) mass spectra obtained in five different mass spectrometers: Finnigan 4000 with a 4500 ion source, Kratos MS-80, Hewlett-Packard 5985 and two Finnigan 4500s. The nine compounds undergo either resonance capture or dissociative capture of an electron at optimum energies ranging from 0.0 to 1.1 eV. The limits of detection generally increased with increasing optimum electron energy. The limit of detection as a function of optimum electron capture energy is expected to provide information about the electron energy distribution in the ion sources. The data showed scatter within and between instruments. The scatter is believed to be due primarily to reactions with low levels of adventitious gases such as oxygen in the ion source. The data also suggested wide variations in electron energies between the instruments. The variation in the electron energy distribution is thought to have been caused by variations in the ion optical fields within the instruments. These results suggest that the requirements for reproducibility in NCI mass spectra at the limit of detection are rigorous control of trace gases in the ion source, control of the electric fields within the source including ion optical fields that penetrate the source aperture control of pressure, temperature and other factors that influence NCI mass spectra.     

Polymorphisms in the interleukin-8 gene in patients with chronic obstructive pulmonary disease

Airway inflammation is the main pathophysiological feature of patients with chronic obstructive pulmonary disease (COPD). Interleukin-8 (IL-8) is a potent chemoattractant for neutrophils and eosinophils. Increased IL-8 levels were observed in bronchoalveolar lavage (BAL) and induced sputum in patients with COPD. To evaluate the role of the IL-8 gene, we genotyped blood samples of 122 COPD-patients and 385 healthy controls for a known polymorphism in the promoter region (-251 A/T) of the IL-8 gene. Additionally, we screened the coding region for further polymorphisms by SSCP analyses. Comparison of the allele and genotype frequencies among each group revealed no significant differences between patients and controls. Although IL-8 plays an important role in the chemotaxis of inflammatory cells, the polymorphisms investigated here do not seem to be involved in the genetic predisposition to COPD.     

Negative ions generated by reactions with oxygen in the chemical ionization source. II. The use of wall-catalyzed oxidation reactions for differentiation of polycyclic aromatic hydrocarbons and their methyl derivatives

Polycyclic aromatic hydrocarbons (PAH) undergo wall-catalyzed oxidation reactions, in conjunction with electron-and ion-molecule reactions, when oxygen is present in the chemical ionization source. Under conditions that promote these wall-catalyzed oxidation reactions (addition of oxygen, elevated ion source temperature) oxidized products are easily detected by measurement of the negative ion chemical ionization (NICI) mass spectra. The NICI mass spectra are dominated by ions that result from electron-capture ionization of oxidation products such as ketones, quinones and anhydrides. In this study the NICI mass spectra of 30 PAH and 46 methyl-substituted PAH were measured. These spectra can be used to differentiate certain isomeric PAH based upon differences in molecular structure. Of particular interest are ions that appear in the spectra of methyl-substituted PAH, which can provide information regarding the position of methyl substituents.     

Infrared molecular beam depletion spectroscopy of size-selected methanol clusters

Molecular beam depletion spectroscopy has been employed to study the dissociation of small methanol clusters in the spectral region between 1000 and 1100 cm^?1 which covers thev ₈ CO stretch (1033.5 cm^?1) and thev ₇ CH₃ rock (1074.5 cm^?1) monomer vibrations. Size selection has been achieved by dispersing the (CH₃OH) _n cluster beam by a secondary He beam. Aside from the recently published CH₃OH dimer absorption bands at 1026.5 and 1051.6 cm^?1 which are assigned to the excitation of the CO stretching vibrations in the non-equivalent subunits of the hydrogen-bonded complex, a previously unobserved band was found at 1071.3 cm^?1. This absorption band is attributed to the excitation of the CH₃ rocking vibration in the dimer. It appears that this transition which is very weak in the free methanol monomer receives substantial oscillator strength due to the intermolecular interaction in the complex. A splitting of this band could not be observed. The trimer and tetramer spectra feature single peaks for the CO stretching vibration being centered at 1042.2 cm^?1 and 1044.0 cm^?1, respectively. This observation is consistent with the cyclic structures of these species. The trimer and tetramer rocking vibrations are observed near 1060.5 cm^?1 but cannot be localized exactly, due to a gap in the CO₂ laser tuning range.