Journal article
Reversible Photohydration of Trenbolone Acetate Metabolites: Mechanistic Understanding of Product-to-Parent Reversion through Complementary Experimental and Theoretical Approaches
Environmental science & technology, Vol.50(13), pp.6753-6761
07/05/2016
DOI: 10.1021/acs.est.5b03905
PMID: 26800354
Abstract
Photolysis experiments (in H2O and D2O) and quantum chemical calculations were performed to explore the pH-dependent, reversible photohydration of trenbolone acetate (TBA) metabolites. Photohydration of 17α-trenbolone (17α-TBOH) and 17β-trenbolone (17β-TBOH) occurred readily in simulated sunlight to yield hydrated products with incorporated H(+) at C4 and OH(-) at either C5 (5-OH-TBOH) or C12 (12-OH-TBOH) in the tetracyclic steroid backbone. Although unable to be elucidated analytically, theory suggests preferred orientations of cis-12-OH-TBOH (relative to C13 methyl) and trans-5-OH-TBOH, with the former most thermodynamically stable overall. Both experiment and theory indicate limited stability of trans-5-OH-TBOH at acidic pH where it undergoes concurrent, carbocation-mediated thermal rearrangement to cis-12-OH-TBOH and dehydration to regenerate its parent structure. Experiments revealed cis-12-OH-TBOH to be more stable at acidic pH, which is the only condition where its reversion to parent TBA metabolite occurred. At basic pH cis-12-OH-TBOH decayed quickly via hydroxide/water addition, behavior that theory attributes to the formation of a stable enolate resistant to dehydration but prone to thermal hydration. In a noteworthy deviation from predicted theoretical stability, 17α-TBOH photohydration yields major trans-5-OH-TBOH and minor cis-12-OH-TBOH, a distribution also opposite that observed for 17β-TBOH. Because H(+) and OH(-) loss from adjacent carbon centers allows trans-5-OH-TBOH to dehydrate at all pH values, the presumed kinetically controlled yield of 17α-TBOH photohydrates results in a greater propensity for 17α-TBOH reversion than 17β-TBOH. Additional calculations explored minor, but potentially bioactive, trenbolone analogs that could be generated via alternative rearrangement of the acidic carbocation intermediate.
Details
- Title: Subtitle
- Reversible Photohydration of Trenbolone Acetate Metabolites: Mechanistic Understanding of Product-to-Parent Reversion through Complementary Experimental and Theoretical Approaches
- Creators
- Jonas Baltrusaitis - College of Public Health, University of Iowa , Iowa City, Iowa 52242, United StatesEric V Patterson - Department of Chemistry, Stony Brook University , Stony Brook, New York 11794, United StatesMeghan O'Connor - Department of Civil and Environmental Engineering, University of Iowa , 4105 Seamans Center for the Engineering Arts and Sciences, Iowa City, Iowa 52242, United StatesShen Qu - Department of Civil and Environmental Engineering, University of Iowa , 4105 Seamans Center for the Engineering Arts and Sciences, Iowa City, Iowa 52242, United StatesEdward P Kolodziej - Civil and Environmental Engineering, University of Washington , Seattle, Washington 98195, United StatesDavid M Cwiertny - Department of Chemical and Biochemical Engineering, University of Iowa , Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Environmental science & technology, Vol.50(13), pp.6753-6761
- Publisher
- United States
- DOI
- 10.1021/acs.est.5b03905
- PMID
- 26800354
- ISSN
- 0013-936X
- eISSN
- 1520-5851
- Grant note
- P30 ES005605 / NIEHS NIH HHS
- Language
- English
- Date published
- 07/05/2016
- Academic Unit
- Center for Health Effects of Environmental Contamination; Civil and Environmental Engineering; Public Policy Center (Archive); Chemical and Biochemical Engineering
- Record Identifier
- 9983993026602771
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