The support provided by the Chemical Synthesis Program of the Chemistry Division allows the research group of Professor David Goldberg in the Department of Chemistry at Johns Hopkins University to develop a new family of iron-containing compounds that activating nitrogen oxide or NOx species. The chemical changes of NOx species, including nitric oxide and its related molecules nitroxyl (HNO) and nitrite ion (NO2-), are critically important for a number of biochemical processes, including cell signaling, immune response, and therapeutic strategies. Nitric oxide is a key neurotransmitter in the brain and throughout the nervous system. There is also significant current interest in the role of HNO in the brain and how it is generated. In this project, Dr. Goldberg and his group construct new iron complexes that bind and react with NOx species. They carry out chemical changes on these molecules related to enzymatic processes. Graduate and undergraduate students are educated and trained in experimental chemical science. An outreach program for students underrepresented in science involving a Baltimore City high school is underway.
The synthesis of a new family of polydentate ligands and their related nonheme iron complexes is under investigation for the binding and activation of NOx species. The oxidative and reductive transformations of several forms of NOx are examined. The observed reactivity is related to enzymatic processes that occur in iron-containing nitric oxide reductases, nitrite reductases, and nitric oxide dioxygenases. In addition, the fundamental reactivity of NOx species, which are potent signaling molecules, is important to a range of processes in the brain and nervous system. Through ligand design, the steric and electronic properties at the metal center are controlled. The study of these complexes may provide insights regarding how structure relates to function in iron-mediated NOx reactivity. Specific efforts will focus on the reduction of NO to NO-/HNO and N2O, the oxidation of NO to NO2- and NO3-, and the reduction of nitrite (NO2-) by biologically relevant reducing agents. The educational plans include an outreach program to a local Baltimore City high school that provides a hands-on laboratory experience.
