HNO, NO, and RSNO Formation and Reactivity at Non-Heme Sites

Georgetown University, Washington DC

Investigators

Abstract

This award in the Chemistry of Life Processes (CLP) program supports work by Professor Timothy H. Warren at Georgetown University to carry out fundamental studies on the generation and interconversion of nitric oxide (NO) and its biochemical relatives S-nitrosothiols (RSNO) and nitroxyl (HNO) at copper ions. Despite the established importance of NO and RSNOs in biochemical signaling pathways leading to physiological responses such as vasodilation along with a rapidly growing interest in HNO, enzymatic pathways for the generation and interconversion of these molecules connected to the biology of nitric oxide are not clearly delineated. A synthetic modeling approach will allow for the detailed examination of transformations among these various NO-derivatives promoted by copper ions in nitrogen-rich coordination environments related to those found in biology. Variation of the copper site along with mechanistic and spectroscopic study will reveal specific factors that promote or inhibit these processes. The straightforward synthesis of copper complexes explored in this work will allow students with very limited synthetic experience, or none at all, such as first year undergraduate (or even high school) students, to contribute to the project. This study will lay a firm foundation upon which to assess the role of copper ions in the biological formation and interconversion of NO, RSNOs, and HNO from naturally occurring precursors such as hydroxylamine (H2NOH) and N-hydroxyguanidines. The heme-free approach will illuminate roles that metal ions other than iron play in the biological processing of nitric oxide and its molecular relatives which are involved in a myriad of physiological events.