@unpublished{pittir10546,
           month = {January},
           title = {Predicting Biological Degradation and Toxicity of Steroidal Estrogens},
          author = {William Barr},
            year = {2012},
            note = {The document itself counting copyright and thesis data (counted as roman numerals) is 101 pages.  The actual thesis is 87 pages},
        keywords = {ethinylestradiol, molecular orbital theory, estrogenicity, human estrogen receptor, biodegradation, estrogen receptor enzyme},
             url = {http://d-scholarship-dev.library.pitt.edu/10546/},
        abstract = {This study was to construct a model to predict a variety of biological transformations of Ethinylestradiol
(EE2) using electronic theory and to analyze the estrogenic potential of EE2 and its metabolites. As a
secondary goal, Frontier Electron Density (FED) theory was applied to the natural steroidal estrogens,
estrone (E1), estradiol (E2) and estriol (E3) to determine if similar initiating reactions could be expected.
Electron density profiles were calculated for EE2 metabolites to determine possible metabolic pathways
up to the cleavage of the first ring. The pathways predicted in this study assume that enzymes commonly
found in wastewater treatment systems will be available to attack EE2 and each metabolite. Predictive
pathways were generated for EE2 based on the electron density and well established degradation rules. A
number of metabolites were shown to be consistent with FED theory.
There are many methods available for effectively calculating the electron density of a given molecule.
Calculations were carried out on the Pittsburgh Supercomputer (PSC) using the computational chemistry
software Gaussian 03. Two molecular orbital theories available for use in Gaussian 03 were used and
results compared to determine if the level of theory significantly affected the accuracy of the electron
density calculations. In the beginning of this study only one theory was used but after studying the
available theories in more detail I implemented a theory that was shown to be more accurate in literature.
Using this information and well established degradation rules, metabolic pathways leading up to the first
ring cleavage were predicted. Experimentally measured metabolites appear in the predicted pathways.
In order to evaluate the environmental impacts of steroidal estrogens and their subsequent metabolites the
estrogenic potential is calculated using chemaxon software. The estrogenic potential was estimated for
EE2 and each of its metabolites both predicted and experimental as well as E1, E2 and E3 and known
experimentally measured metabolites that are similar to EE2. In all cases the estrogenic potential of the
metabolites indicate that they have a lower toxicity than the parent compounds but may still retain
estrogenic potential after biotransformation.}
}