Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.

The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process.

Formation of carbon-carbon bonds in the photochemical alkylation of polycyclic aromatic hydrocarbons.

The reaction of polycyclic aromatic hydrocarbons (PAHs) with alkanes was examined in the presence of ultraviolet (UV) light under model prebiotic Earth and interstellar medium (ISM) conditions. We observed the formation of alkylated PAHs from a variety of PAHs and alkanes, which was caused by the absorption of UV light by the PAH molecule. Photoalkylation occurred in PAHs and alkanes in solution, in thin films in contact with simulated ocean water, and in matrices simulating ISM conditions. Photoalkylation occurred readily, with significant product yields within 5 h of irradiation. Because alkanes and PAHs are presumed to be part of the organic inventory in the ISM and on the early Earth, we propose that this photoalkylation reaction is a plausible pathway for the formation of carbon-carbon bonds in both these environments.

PAH sorption mechanism and partitioning behavior in lampblack-impacted soils from former oil-gas plant sites.

This study assessed polycyclic aromatic hydrocarbon (PAH) association and aqueous partitioning in lampblack-impacted field soils from five sites in California that formerly housed oil-gas process operations. Lampblack is the solid residue resulting from the decomposition of crude oil at high temperatures in the gas-making operation and is coated or impregnated with oil gasification byproducts, among which PAHs are the compounds of the greatest regulatory concern. A suite of complementary measurements investigated the character of lampblack particles and PAH location and the associated effects on PAH partitioning between lampblack and water. PAH analyses on both whole samples and density-separated components demonstrated that 81-100% of PAHs in the lampblack-impacted soils was associated with lampblack particles. FTIR, 13C NMR, and SEM analyses showed that oil-gas lampblack solids comprise primarily aromatic carbon with soot-like structures. A free-phase aromatic oil may be present in some of the lampblack soils containing high PAH concentrations. Comparable long-term aqueous partitioning measurements were obtained with an air-bridge technique and with a centrifugation/alum flocculation procedure. Large solid/water partition coefficient (Kd) values were observed in samples exhibiting lower PAH and oil levels, whereas smaller Kd values were measured in lampblack samples containing high PAH levels. The former result is in agreement with an oil-soot partitioning model, and the latter is in agreement with a coal tar-water partitioning model. Lampblack containing high PAH levels appears to exhaust the sorption capacity of the soot-carbon, creating a free aromatic oil phase that exhibits partitioning behavior similar to PAHs in coal tar. This study improves mechanistic understanding of PAH sorption on aged lampblack residuals at former oil-gas sites and provides a framework for mechanistic assessment of PAH leaching potential and risk from such site materials.