Energetics of the metabolic production of (E,E)-muconaldehyde from benzene via the intermediates 2,3-epoxyoxepin and (Z,Z)- and (E,Z)-muconaldehyde: Ab initio molecular orbital calculations

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00035a016· OSTI ID:6848458

Greenberg, A ^[1]; Bock, C W ^[2]; George, P; Glusker, J P ^[3]

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1. Rutgers Univ., New Brunswick, NJ (United States)
2. Philadelphia College of Textiles and Science, PA (United States)
3. Fox Chase Cancer Center, Philadelphia, PA (United States)

To assess the feasibility of the pathway set out in the title, we have carried out ab initio molecular orbital calculations of the energies of cisoid- and transoid-2,3-epoxyoxepin and the eZzZz-, eZeZz-, eEeZe-, eEeEz-, and eEeEe-conformers of muconaldehyde at the MP2/6-31G[sup *] (frozen core, valence orbitals active) level with full geometry optimization using the split-valence RHF/6-31G[sup *]//RHF/6-31G[sup *] level, reaction energies (that would correspond to gas phase data at 298 K) have been evaluated. The muconaldehyde conformers are lower in energy than the epoxyoxepin, i.e., are formed exothermically, and in accord with experiment, the Z,Z-conformers are less stable than the E,Z, and the E,Z less stable than the E,E. In addition, we have characterized the transition state for the fission of the C-O bond in the epoxy ring and the C-O bond in the oxepin ring of transoid-2,3-epoxyoxepin, thereby generating eZzZz-muconaldehyde. With an activation energy of 16.5 kcal mol[sup [minus]1] the half-life of the epoxy-oxepin is very short at the temperatures employed in the experiments, less than 1 min, which explains why it has not been detected. To gain some insight into the isomerization about the carbon-carbon double bonds in the muconaldehyde conformers, we have examined the possible involvement of 2-formyl-2H-pyran and cyclobutene-3,4-dicarboxyaldehyde as intermediates. In model reactions simulating the microsomal monooxygenase system, the formation of benzene oxide and of the epoxyoxepin are found to be very favorable exothermic processes. 60 refs., 4 figs., 2 tabs.

• OSTI ID: 6848458
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 6:5; ISSN 0893-228X; ISSN CRTOEC
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTIVATION ENERGY
ALDEHYDES
AROMATICS
BENZENE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
CHEMICAL ANALYSIS
CHEMICAL BONDS
CHEMICAL REACTIONS
DOUBLE BONDS
ENERGY
HYDROCARBONS
ISOMERIZATION
KINETICS
METABOLISM
ORGANIC COMPOUNDS
QUALITATIVE CHEMICAL ANALYSIS
REACTION INTERMEDIATES
REACTION KINETICS
TOXICITY