Ligands Designed for Ruthenium Nitrosyl Transport

Since the award of the Nobel Prize for the discovery that endothelium-derived relaxing factor is nitric oxide, there has been an enormous amount of research into its role in other physiological processes. Nitric oxide has been shown to be involved in neurotransmission, respiration and fighting infection, among many other functions. While nitric oxide is essential to life, its overproduction can be deadly. For example, toxic shock results from overproduction of nitric oxide during infection and can cause a fatal drop in blood pressure. Since many of nitric oxide's biological functions involve iron complexes, our initial goals were to investigate iron complexes that might be used as nitric oxide scavengers. Since nitric oxide is also inhibits the growth of certain types of tumors, we are interested in developing ruthenium nitrosyl complexes that can transport nitric oxide to a tumor site and release NO photolytically. This document describes the preparation and characterization of several bis-carboxamido bis-pyridyl and bis-carboxamido bis-pyrazyl ligands. The deprotonated carboxamido group is expected to activate the RuNO moiety to photolytic loss of nitric oxide and then stabilize the ruthenium-solvent complex that remains after photolysis. The pyridyl/pyrazyl groups will enforce chelation. Systematic variation of the ligand backbone will provide insight into the factors that govern photolytic loss of nitric oxide. Characterization of some of the respective ruthenium nitrosyl complexes is discussed