title: 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.
authors: Department of Civil and Environmental Engineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States.
authors: William J
authors: WJ
authors: Barr
authors: Taewoo
authors: T
authors: Yi
authors: Diana
authors: D
authors: Aga
authors: Orlando
authors: O
authors: Acevedo
authors: Willie F
authors: WF
authors: Harper
mesh_terms: D003198:Computer Simulation; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D015394:Molecular Structure
chemical_list: D004798:Enzymes; D004997:Ethinyl Estradiol