Styrene is oxidized to styrene oxide and benzaldehyde when incubated with horseradish peroxidase, H2O2, and 4-methylphenol. Styrene oxide is not formed in the absence of any of these reaction components or of molecular oxygen. The coupling products 2-(4-methylphenoxy)-1-phenylethane, 2-(4-methylphenoxy)-1-phenylethan-1-ol, and 2-(4-methylphenoxy)-2-phenylethan-1-ol are not formed, but the ortho-linked dimer of 4-methylphenol is a major product. The epoxide oxygen is labeled in the presence of 18O2 but not H218O2. Styrene oxide formation is not inhibited by mannitol or superoxide dismutase. The stereochemistry of trans-[1-2H]styrene is partially scrambled in the epoxide product. EPR signals attributable to the 2,4-dihydroxy-5-methylphenoxy radical, a product of the oxidation of 4-methylcatechol, are observed if Zn2+ is added to stabilize the radical. This radical is only detected in the presence of styrene. The results imply that styrene is epoxidized by the hydroperoxy radical generated by addition of molecular oxygen to the 4-methylphenoxy radical. The epoxidation mimics the chemistry proposed to occur in the protein-mediated cooxidation of styrene by hemoglobin and myoglobin.

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IntroductionImproving postoperative patient recovery after cardiac surgery is a priority, but our current understanding of individual variations in recovery and factors associated with poor recovery is limited. We are using a health-information exchange platform to collect patient-reported outcome measures (PROMs) and wearable device data to phenotype recovery patterns in the 30-day period after cardiac surgery hospital discharge, to identify factors associated with these phenotypes and to investigate phenotype associations with clinical outcomes.Methods and analysisWe designed a prospective cohort study to enrol 200 patients undergoing valve, coronary artery bypass graft or aortic surgery at a tertiary centre in the USA. We are enrolling patients postoperatively after the intensive care unit discharge and delivering electronic surveys directly to patients every 3 days for 30 days after hospital discharge. We will conduct medical record reviews to collect patient demographics, comorbidity, operative details and hospital course using the Society of Thoracic Surgeons data definitions. We will use phone interview and medical record review data for adjudication of survival, readmission and complications. We will apply group-based trajectory modelling to the time-series PROM and device data to classify patients into distinct categories of recovery trajectories. We will evaluate whether certain recovery pattern predicts death or hospital readmissions, as well as whether clinical factors predict a patient having poor recovery trajectories. We will evaluate whether early recovery patterns predict the overall trajectory at the patient-level.Ethics and disseminationThe Yale Institutional Review Board approved this study. Following the description of the study procedure, we obtain written informed consent from all study participants. The consent form states that all personal information, survey response and any medical records are confidential, will not be shared and are stored in an encrypted database. We plan to publish our study findings in peer-reviewed journals.

Incubation of 3-(2-phenylethyl)-4-methylsydnone (PMS) with liver microsomes from phenobarbital-pretreated rats or with reconstituted cytochrome P-450b results in loss of the enzyme chromophore. Chromophore loss is NADPH-dependent even though the sydnone decomposes by an oxygen- but not enzyme-dependent process to give pyruvic acid and, presumably, the (2-phenylethyl)diazonium cation. N-(2-Phenylethyl)protoporphyrin IX and N-(2-phenylethenyl)protoporphyrin IX have been isolated from the livers of rats treated with PMS. Both deuteriums are retained in the N-(2-phenylethyl) adduct derived from 3-(2-phenyl[1,1-2H]ethyl)-4-methylsydnone, but one deuterium is lost in the N-(2-phenylethenyl) adduct. The N-(2-phenylethyl) to N-(2-phenylethenyl) adduct ratio is increased by deuterium substitution. No spectroscopically detectable intermediates precede chromophore loss in incubations of reconstituted cytochrome P-450b with PMS. Electron paramagnetic resonance (EPR)-spin trapping studies show that carbon radicals are formed in incubations of the sydnones with liver microsomes but by a process that is independent of chromophore destruction. It is proposed that the 2-phenylethyl radical formed by electron transfer to the sydnone-derived (2-phenylethyl)diazonium cation adds to the prosthetic heme group to give the N-(2-phenylethyl) adduct. This alkylation reaction is similar to that observed with (2-phenylethyl)hydrazine. Autoxidation of the Fe-CH(CH2Ph)-N bridged species expected from insertion of 2-phenyldiazoethane into one of the heme Fe-N bonds is proposed to explain the unprecedented introduction of a double bond into the N-(2-phenylethenyl) adduct.

3‐[2‐(2,4,6‐Trimethylphenyl)thioethyl]‐4‐methylsydnone was shown to be a potent porphyrinogenic agent in chick embryo liver cells. The accumulation of protoporphyrin IX was consistent with the finding that ferrochelatase activity was inhibited. 3‐Benzyl‐4‐phenylsydnone did not inhibit ferrochelatase activity and protoporphyrin IX was found to constitute only a minor fraction of the porphyrins. These results support the idea that the porphyrinogenicity of 3‐[2‐(2,4,6‐trimethylphenyl)thioethyl]‐4‐methylsydnone is due to its catalytic activation by cytochrome P‐450 leading to heme alkylation and formation of N‐vinylprotoporphyrin IX which inhibits ferrochelatase.