Using Electronic Theory To Identify Metabolites Present in 17α-Ethinylestradiol Biotransformation Pathways

Abstract

This research used electronic theory to model the biotransformation of 17α-ethinylestradiol (EE(2)) under aerobic conditions in mixed culture. The methodology involved determining the Frontier Electron Density (FED) for EE(2) and various metabolites, as well as invoking well-established degradation rules to predict transformation pathways. We show that measured EE(2) metabolites are in good agreement with what is expected based on FED-based modeling. Initiating reactions occur at Ring A, producing metabolites that have been experimentally detected. When OH-EE(2) and 6AH-EE(2) are transformed, Ring A is cleaved before Ring B. The metabolites involved in these pathways have different estrogenic potentials, as implied by our analysis of the log P values and the hydrogen bonding characteristics. The OH-EE(2) and 6AH-EE(2) transformation pathways also show redox-induced electron rearrangement (RIER), where oxidation reactions lead to the reduction of carbon units present along the bond axis. Sulfo-EE(2) appears to be difficult to biotransform. These findings clarify theoretical and practical aspects of EE(2) biotransformation.

Catalytic oxidative degradation of 17α-ethinylestradiol by FeIII-TAML/H2O2: Estrogenicities of the products of partial, and extensive oxidation

“…The EE 2 molecular structure is similar to E 2 , and the ethynyl group does not affect the frontier electron densities much, suggesting that EE 2 should behave in a similar manner. Using electronic theory to model the biotransformation of EE 2 under aerobic conditions, Barr et al also proposed that Ring A is cleaved before Ring B (Barr et al, 2011). The present study uses the UHF method to calculate the FED of EE 2 .…”

Using Electronic Theory to Examine Horseradish Peroxidase-Mediated Coupling of Estradiol

“…This is redox-induced electron rearrangement (RIER), which happens when nearby electron orbitals reconfigure so that the FED of a particular carbon atom may increase. RIER has been observed computationally in previous efforts [11], but this account is the first in which RIER is shown to happen during the course of an oxidative polymerization.…”

“…Most recently Harper [10] successfully predicted where ethinyl estradiol would be degraded by first determining the electron distribution. Yi [11] carried out a similar study with trimethoprim. This recent work is now showing that biologically-mediated electron transfer reactions can be understood using FED-based approaches and this means that we are close to being able to carry out a priori predictions concerning how steroidal compounds will be transformed in the environment.…”

Aerobic Biodegradation of Four Groups of Steroid Hormones in Activated Sludge

“…Microbial processes play an essential role in steroid degradation. Such processes have been particularly well documented for the microbiological degradation of estrogens and androgens [14][15][16][17][18][19]. However, for progestogens and glucocorticoids, most studies have been mainly concerned about their concentrations in WWTP influents and effluents and receiving waters.…”