IMAGING EPIGENETIC MODIFICATIONS
Epigenetic modifications enable dynamic regulation of gene expression in response to environmental factors without altering the underlying genetic sequence. Known mechanisms include DNA methylation at cytosine and an array of organic modifications to histone N-termini. Such modifications, though necessary (e.g., cellular differentiation), have been implicated in a variety of disease pathologies, including addiction, diabetes, and cancer. Using well-established molecular imaging techniques, we are developing simple, yet innovative tools able to differentiate distinct epigenetic changes noninvasively. The ability to do so will further our understanding regarding these fundamental processes, provide useful prognostic information, and guide future therapeutic designs.
SYNTHETIC IRON(IV)-OXO COMPLEXES
Mononuclear nonheme iron enzymes that activate molecular oxygen catalyze crucial oxidative transformations (e.g., DNA demethylation). Despite their diverse chemistries, these metalloenzymes share a characteristic 2-His-1-carboxylate facial triad that supports a high-spin iron(IV)-oxo intermediate responsible for substrate oxidation. Synthetic strategies to generate this electronic structure include enforcing a trigonal bipyramidal geometry and sterically weakening a pseudo-octahedral ligand field about the metal center. These approaches, however, utilize nitrogen-rich ligand platforms that omit the 2-His-1-carboxylate structural motif. To better understand the features controlling iron(IV)-oxo reactivity, we are constructing weak-field oxygen-rich ligands that will structurally mimic mononuclear nonheme iron enzyme active sites. Select candidates will be applied to the fields of C-H activation and sustainable catalysis.