Journal article
Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration
Environmental science & technology, Vol.50(14), pp.7480-7488
07/19/2016
DOI: 10.1021/acs.est.6b02608
PMID: 27356268
Abstract
Despite its wide use as a veterinary pharmaceutical, environmental fate data is lacking for altrenogest, a potent synthetic progestin. Here, it is reported that direct photolysis of altrenogest under environmentally relevant conditions was extremely efficient and rapid (half-life ∼25 s). Photolysis rates (observed rate constant kobs = 2.7 ± 0.2 × 10(-2) s(-1)) were unaffected by changes in pH or temperature but were sensitive to oxygen concentrations (N2-saturated kobs = 9.10 ± 0.32 × 10(-2) s(-1); O2-saturated kobs = 1.38 ± 0.11 × 10(-2) s(-1)). The primary photoproduct was identified as an isomer formed via an internal 2 + 2 cycloaddition reaction; the triplet lifetime (8.4 ± 0.2 μs) and rate constant (8 × 10(4) s(-1)) of this reaction were measured using transient absorption spectroscopy. Subsequent characterization determined that this primary cycloaddition photoproduct undergoes photohydration. The resultant photostable secondary photoproducts are subject to thermal dehydration in dark conditions, leading to reversion to the primary cycloaddition photoproduct on a time scale of hours to days, with the photohydration and dehydration repeatable over several light/dark cycles. This dehydration reaction occurs more rapidly at higher temperatures and is also accelerated at both high and low pH values. In vitro androgen receptor (AR)-dependent gene transcriptional activation cell assays and in silico nuclear hormone receptor screening revealed that certain photoproducts retain significant androgenic activity, which has implications for exposure risks associated with the presence and cycling of altrenogest and its photoproducts in the environment.
Details
- Title: Subtitle
- Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration
- Creators
- Kristine H Wammer - Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United StatesKyler C Anderson - Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United StatesPaul R Erickson - Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, SwitzerlandSarah Kliegman - Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, SwitzerlandMarianna E Moffatt - Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United StatesStephanie M Berg - Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United StatesJackie A Heitzman - Department of Biology, University of St. Thomas , St. Paul, Minnesota 55105, United StatesNicholas C Pflug - Department of Chemistry, University of Iowa , Iowa City, Iowa 52242, United StatesKristopher McNeill - Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, SwitzerlandDalma Martinovic-Weigelt - Department of Biology, University of St. Thomas , St. Paul, Minnesota 55105, United StatesRuben Abagyan - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , 9500 Gilman, La Jolla, California 92093-0747, United StatesDavid M Cwiertny - Department of Civil and Environmental Engineering, University of Iowa , Iowa City, Iowa 52242, United StatesEdward P Kolodziej - Department of Civil and Environmental Engineering, University of Washington , Seattle, Washington 98195-2700 United States
- Resource Type
- Journal article
- Publication Details
- Environmental science & technology, Vol.50(14), pp.7480-7488
- DOI
- 10.1021/acs.est.6b02608
- PMID
- 27356268
- NLM abbreviation
- Environ Sci Technol
- ISSN
- 1520-5851
- eISSN
- 1520-5851
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS
- Language
- English
- Date published
- 07/19/2016
- Academic Unit
- Center for Health Effects of Environmental Contamination; Civil and Environmental Engineering; Public Policy Center (Archive); Chemical and Biochemical Engineering
- Record Identifier
- 9983992001302771
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