| Summary: | Nitric oxide (NO) has been shown to both promote and inhibit tumor growth depending on its concentration. Ruthenium nitrosyl complexes have been suggested as catalytic NO donors. Catalysis may provide prolonged and elevated NO donation, which can lead to tumor regression. The mechanism of NO release and catalytic activity of [Ru(cyclam)(NO(Cl]²⁺ was explored. Spectroscopic (UV-vis, EPR, IR, mass spec) analysis validated the proposed ruthenium-based catalytic cycle. However, detection by chemiluminescence revealed that reduction of [Ru(cyclam)(NO)Cl]²⁺ does not lead to NO release. Crystallographic analysis showed that a dinitrogen dimer, [Cl(cyclam)Ru(μ-N₂)Ru(cyclam)Cl]²⁺ is formed upon reduction, which could explain the lack of NO release. Formation of the dinitrogen bridged dimer is supported by IR spectroelectrochemistry, which shows an N-N stretching frequency at 2050 cm⁻¹ following electrochemical reduction. HNO has recently emerged as an important pharmacological agent, but HNO can be autoxidized to a cytotoxic species. Despite extensive analysis, the identity of the autoxidation product remains unknown. HNO autoxidation is isoelectronic with the physiologically relevant reaction of NO and superoxide (O₂⁻) producing peroxynitrite (ONOO⁻). The reactivity of synthetic ONOO⁻ was compared to that of the products of autoxidation of HNO and nitroxyl (NO⁻) with a dual purpose in mind. The first was to compare the chemistry of HNO and NO⁻ autoxidation, while the second was to compare the chemistry of two preparations of ONOO⁻. Analysis indicates that aerobic decomposition of IPA/NO (Na[(CH₃)₂CHNHN(O)NO], sodium 1 (N isopropylamino)diazen-1-ium-1,2-diolate) in pH 13 provides a more reliable preparation of ONOO⁻ compared to the more common synthetic method. Furthermore, HNO autoxidation leads to an oxidant distinct from ONOO⁻, regardless of formation pathway.
|
|---|
