10.1021/acs.est.6b02608.s001
Kristine H. Wammer
Kristine H.
Wammer
Kyler C. Anderson
Kyler C.
Anderson
Paul R. Erickson
Paul R.
Erickson
Sarah Kliegman
Sarah
Kliegman
Marianna E. Moffatt
Marianna E.
Moffatt
Stephanie M. Berg
Stephanie M.
Berg
Jackie A. Heitzman
Jackie A.
Heitzman
Nicholas C. Pflug
Nicholas C.
Pflug
Kristopher McNeill
Kristopher
McNeill
Dalma Martinovic-Weigelt
Dalma
Martinovic-Weigelt
Ruben Abagyan
Ruben
Abagyan
David M. Cwiertny
David M.
Cwiertny
Edward P. Kolodziej
Edward P.
Kolodziej
Environmental
Photochemistry of Altrenogest: Photoisomerization
to a Bioactive Product with Increased Environmental Persistence via
Reversible Photohydration
American Chemical Society
2016
dehydration
cycloaddition photoproduct
altrenogest
hormone receptor screening
k obs
2 cycloaddition reaction
AR
2016-06-29 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Environmental_Photochemistry_of_Altrenogest_Photoisomerization_to_a_Bioactive_Product_with_Increased_Environmental_Persistence_via_Reversible_Photohydration/3479300
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 <i>k</i><sub>obs</sub> = 2.7 ± 0.2 × 10<sup>–2</sup> s<sup>–1</sup>) were unaffected by changes in pH or temperature but were sensitive
to oxygen concentrations (N<sub>2</sub>-saturated <i>k</i><sub>obs</sub> = 9.10 ± 0.32 × 10<sup>–2</sup> s<sup>–1</sup>; O<sub>2</sub>-saturated <i>k</i><sub>obs</sub> = 1.38 ± 0.11 × 10<sup>–2</sup> s<sup>–1</sup>). 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<sup>4</sup> s<sup>–1</sup>) 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.