Markell Lomax

In the Jackson research group, we are interested in understanding the reactivity of metal ions in biology, particularly metal-oxygen intermediates in enzymes. Our approach is to synthesize and study models of enzymatic intermediates in order to understand geometric and electronic structure contributions to reactivity. My project is to generate models of intermediates in the enzymes manganese superoxide dismutase (MnSOD) and manganese lipoxygenase (MnLOX). MnSOD is responsible for the disproportionation of superoxide to oxygen and hydrogen peroxide in mitochondria. This reaction is crucial to break down radicals that can be toxic to cells. MnLOX converts polyunsaturated fatty acids to alkyl hydroperoxides through C-H bond activation. Both the MnSOD and MnLOX active sites manage proton-electron transfer reactions using a MnII-OH2/MnIII-OH couple.  In both enzymes the H2O/OH ligands hydrogen bond to nearby amino acids. Though there is hydrogen bonding, the role of these hydrogen bonds on reactivity have been relatively unexplored, so there are gaps in our understanding of the enzymes. I work with model complexes designed to closely resemble the enzyme active site by introducing hydrogen bonding capabilities. Previously, our group compared the kinetic reactivity of systems with a controlled model system without hydrogen bonding to a model system with hydrogen bonding. The goal of my research is to understand more about the thermodynamic properties and reactivity of these model complexes. Using phenolic substrates, I can compare the properties and reactivity of the MnIII-hydroxo complexes and their MnIII-aqua analogues to probe reactivity.