title: Environmental Photochemistry of Altrenogest: Photoisomerization to a Bioactive Product with Increased Environmental Persistence via Reversible Photohydration.
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.
authors.affiliation: Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Kristine H
authors.initials: KH
authors.lastname: Wammer
authors.affiliation: Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Kyler C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, Switzerland.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Erickson
authors.affiliation: Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kliegman
authors.affiliation: Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Marianna E
authors.initials: ME
authors.lastname: Moffatt
authors.affiliation: Department of Chemistry, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Berg
authors.affiliation: Department of Biology, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Heitzman
authors.affiliation: Department of Chemistry, University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Pflug
authors.affiliation: Institute of Biogeochemistry and Pollutant Dynamics, ETH Zürich , CH-8092 Zürich, Switzerland.
authors.forename: Kristopher
authors.initials: K
authors.lastname: McNeill
authors.affiliation: Department of Biology, University of St. Thomas , St. Paul, Minnesota 55105, United States.
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinovic-Weigelt
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , 9500 Gilman, La Jolla, California 92093-0747, United States.
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.affiliation: Department of Civil and Environmental Engineering, University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Cwiertny
authors.affiliation: Interdisciplinary Arts and Sciences, University of Washington, Tacoma , Tacoma, Washington 98402 United States.|Department of Civil and Environmental Engineering, University of Washington , Seattle, Washington 98195-2700 United States.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Kolodziej
mesh_terms: D004777:Environment; D006207:Half-Life; D010777:Photochemistry; D010782:Photolysis; D013696:Temperature