My research lies at the interfaces between traditional inorganic chemistry, organic chemistry, and biochemistry. Two diverse goals are pursued: (1) the development of novel methodology for difficult organic transformations and (2) the production of small molecule sensors capable of detecting reactive oxygen species in biological environments.
Tuning the Regioselectivity of C-H Bond Activation:
Most oxidation processes are indiscriminate with respect to the site and extent of oxidation. The lack of selectivity necessitates the subsequent separation of the target molecule from a number of side-products, consuming a researcher’s time, energy, and patience. What selectivity exists normally results from the characteristics of the substrate. Certain C-H bonds, for instance, may be more susceptible to activation due to either electronic or steric effects. The C-H bonds on tertiary carbons are easier to oxidize than those on secondary carbons. Obtaining products that don’t result from these intrinsic preferences is difficult.
The goal of this project is to tune the regioselectivity of C-H activation through the use of sterically encumbered non-heme iron catalysts. The steric bulk that has been installed on these catalysts will interact with bulkier portions of the substrate in order to guide the catalyzed C-H activation towards the less sterically congested secondary and primary carbons of the substrates.
Gallium-Catalyzed Alkene Oxidation:
Group 13 metals are relatively redox-inactive; correspondingly, they have been used sparingly in oxidative catalysis. Most homogeneous catalysts for the oxidation of alkenes to epoxides use transition metal ions. The reactivity of many of these catalysts is believed to proceed through higher-valent intermediates that can also perform allylic C-H activation and dihydroxylation.
The goal of this project is to investigate gallium(III) complexes with neutral ligands as catalysts for alkene epoxidation. These compounds activate terminal oxidants through their ability to act as Lewis Acids. The redox-inactivity of the metal eliminates many of the alternative pathways that result in the side-reactivity observed for many transition metal analogs. This can facilitate the isolation of the desired epoxide product.
Small Molecule Sensors for Reactive Oxygen Species:
Reactive oxygen species (ROSs) have been implicated in a number of health conditions, including numerous inflammatory, cardiovascular, and neurological pathologies (e.g. Huntington’s and Alzheimer’s diseases). The ability to monitor aberrant oxidative activity within living subjects would be a tremendous boon for medicine, with the potential to improve diagnosis and treatment of the associated diseases. Recently, a number of compounds have been developed to detect ROS activity. Most of these rely on a change in the fluorescent properties of the probe to signal the presence of a ROS. The relatively short wavelengths of light needed to excite the fluorophore limit the application of these sensors to cell cultures and thin tissues.
The goal of this project is to develop redox-active contrast agents for magnetic resonance imaging (MRI) that are capable of detecting ROSs within whole-body subjects. The currently explored contrast agents are mononuclear manganese(II) complexes with redox-active ligands. Upon oxidation, the relaxivity of the compound changes, providing a signal that can be detected and quantified by MRI.