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CHO+ ions are made by electron impact on CD3OH in the source (ICR1) of a tandem ion cyclotron resonance spectrometer. These ions are injected into a differentially pumped analysis cell (ICR2) where they are reacted with a number of small molecules. The internal energy distribution in the CHO+ ions is obtained using total reactivity studies with neutral molecules of varying proton affinities. About 40% of the CHO+ ions react with D2 either by proton transfer to form D2H+ or isotopic exchange to form CDO+ ions. A series of experiments are performed that conclusively show these ions are the HOC+ isomer and the exchange is due to the catalytic isomerization reaction HOC++D2→DCO++HD which is approximately 37 kcal/mol exothermic. The product DCO+ ions are vibrationally cool indicating the reaction releases most of its energy as kinetic energy. Absolute rate constants for reactions of CHO+ ions with the neutrals 13CO, 15N2, CO2, O2, D2, and Ar are reported. HOC+ reacts with D2 at about 30% of the collision rate. This rate decreases with increasing HOC+ kinetic energy in the range 0.025 to 0.44 eV. The two products of the reaction are D2H+/CO and DCO+/HD with DCO+/HD comprising ∼42% of the products for the HOC+ ions formed from CD3OH. Phase space theory calculations are performed to determine the barrier to catalytic isomerization. The data are best fit with a barrier between 0.0 and -0.05 eV relative to the HOC+/D2 asymptotic energy. A barrier of this magnitude yields reaction rate constants at interstellar temperatures of at least 10% of the collision rate constant (i.e., k>1×10-10 cm3/s), and could explain why so little HOC+ is observed in interstellar clouds. [ABSTRACT FROM AUTHOR]

1. Ponesimod [(R)-5-[3-chloro-4-(-2,3-dihydroxy-propoxy)-benzylidene]-2-propylimino-3-o-tolyl-thiazolidin-4-one] is an orally administered, selective S1P1 receptor modulator that blocks the egress of lymphocytes from lymphoid organs and reduces the availability of circulating effector T/B-cells. 2. The mass balance, pharmacokinetics and metabolism of 40 mg 14C-ponesimod were investigated in six healthy male subjects. The total radioactivity in whole blood, plasma, urine, faeces and expired CO2 was determined by liquid scintillation counting. Metabolite profiling was performed by high-performance liquid chromatography and detection by mass spectrometry. 3. The majority of the radioactivity (% of administered dose) was recovered in faeces (57.3-79.6%), followed by urine (10.3-18.4%) and a small proportion in CO2 from expired air (0.6-1.9%). The average cumulative recovery (mass balance) of 14C-associated radioactivity in faeces and urine was 77.9% of the administered dose. Unchanged ponesimod made up 25.9% of total radioactivity in faeces; none was detected in urine. Ponesimod was extensively metabolised and two pharmacologically inactive metabolites, M12 (ACT-204426) and M13 (ACT-338375), were detected in the circulation. M12 corresponded to 8.1% and M13 to 25.7% of the total drug-related radioactive exposure (AUC0-∞) in plasma. M12 was highly abundant in faeces (22.3% of total radioactivity) and to a smaller extent in urine (2.5% of total radioactivity). [ABSTRACT FROM AUTHOR]

Using the relative abundance of metastable ions, collisional activation spectra, field ionization kinetic measurements, isotopic labelling, appearance energy and kinetic energy release data, it is shown that linear alkyne radical cations with more than six carbon atoms do not isomerize to equilibrating structures prior to decomposition. At the shortest ion lifetimes the molecular ions of linear alkynes decompose mainly by simple β-bond fission which allows an unequivocal localization of the triple bond. At medium ion lifetimes fragmentation occurs predominantly via a McLafferty rearrangement, while at long ion lifetimes competing alkyl losses prevail. These alkyl losses occur via cyclic intermediates leading to thermochemically stable cycloalkenyl ions. All these reactions occur with a high specificity with respect to the carbon and hydrogen atoms involved and are preceded by little or no hydrogen exchange reactions. [ABSTRACT FROM AUTHOR]

1. Ponesimod [(R)-5-[3-chloro-4-(-2,3-dihydroxy-propoxy)-benzylidene]-2-propylimino-3-o-tolyl-thiazolidin-4-one] is an orally administered, selective S1P1 receptor modulator that blocks the egress of lymphocytes from lymphoid organs and reduces the availability of circulating effector T/B-cells. 2. The mass balance, pharmacokinetics and metabolism of 40 mg (14)C-ponesimod were investigated in six healthy male subjects. The total radioactivity in whole blood, plasma, urine, faeces and expired CO2 was determined by liquid scintillation counting. Metabolite profiling was performed by high-performance liquid chromatography and detection by mass spectrometry. 3. The majority of the radioactivity (% of administered dose) was recovered in faeces (57.3-79.6%), followed by urine (10.3-18.4%) and a small proportion in CO2 from expired air (0.6-1.9%). The average cumulative recovery (mass balance) of (14)C-associated radioactivity in faeces and urine was 77.9% of the administered dose. Unchanged ponesimod made up 25.9% of total radioactivity in faeces; none was detected in urine. Ponesimod was extensively metabolised and two pharmacologically inactive metabolites, M12 (ACT-204426) and M13 (ACT-338375), were detected in the circulation. M12 corresponded to 8.1% and M13 to 25.7% of the total drug-related radioactive exposure (AUC0-∞) in plasma. M12 was highly abundant in faeces (22.3% of total radioactivity) and to a smaller extent in urine (2.5% of total radioactivity).