Iridium (III) Complexes as Sensors for Cytochrome P450 Enzymes
2022 Undergraduate Research Symposium
Justin Ahrens (chemistry)
Graduate co-author: Maddy Denison
Faculty mentor: Jeremy Kodanko
Abstract
The main goal of this project is to use IrIII complexes to monitor cytochrome P450 (CYP) activity. CYP P450 metabolism determines how quickly drugs are excreted from the body and what kind of dose is required for pharmaceuticals to be effective.
Existing probes for CYPs are non-fluorescent, but when CYPs metabolize them, they are "turned on" and fluoresce. Even though these probes are able to monitor metabolism, once they are metabolized and "turned on" they cannot be reversed or turned off. Therefore, this is no current way to monitor dynamic changes in CYP activity continuously over time.
The Kodanko laboratory is addressing this unmet need by developing IrIII complexes that are reversible sensors of CYP enzymes. A chiral resolution strategy with enantioenriched ligands was used to prepare four analogs of IrIII complexes with different stereochemistry. These complexes were evaluated as emissive sensors in human liver hepatocytes to establish which IrIII complex is the lead compound for sensing CYP in living cells. Results from this multi-disciplinary study will be reported.
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Justin Ahrens and Maddy Denison: Iridium (III) Complexes as Sensors for Cytochrome P450 Enzymes