Recent discoveries in the roles of nitric oxide in humans have generated tremendous interest in biologically active transition metal nitrosyl complexes. Among them, the non-heme iron nitrosyl complexes have been identified as products of biosynthetic evolution of nitric oxide, suggested as nitric oxide storage, and found to be responsible for several important biological functions. However, these studies were limited to EPR and IR identification of these complexes in solution and the structures of these compounds were not well characterized and understood. The proposed research is to synthesize non-heme iron nitrosyl compounds that mimic biologically active non-heme iron nitrosyls by using specially selected ligands that are soluble in water and have the potential to interact with DNA. The reaction mechanisms and structures of these complexes will be studied using a combination of spectroscopic methods, such as FT-IR, EPR, NMR, UV-vis, X-ray crystallography and electrochemical techniques. Chemical, photolytic and electrochemical methods will be used to achieve the NO release from these complexes and the quantitative NO release kinetics will be investigated by applying nanosecond laser photolysis techniques. Potential biological activities will also be tested. These results will provide information on the structures of biologically activ non-heme iron nitrosyls, thus helping the neuroscience, physiology and medicinal research communities understand the diverse biological functions of nitric oxide and its metal complexes, some of which include controlling blood pressure, preventing platelet aggregation, acting as biological messengers and immune system cytotoxic agents, and playing a role in long-term memory. The kinetic data and the biological activity testing results will be used to identify the NO-releasing metal complexes, which can be used in cardiovascular muscle relaxation, cancer therapy, pharmacokinetic studies, and other medicinal applications.
The proposed research is to synthesize and isolate compounds that mimic biologically active non-heme iron-nitrosyl complexes, study their structures, investigate the conditions for NO release, and test their biological activities. The knowledge generated from this study will assist in selecting NO releasing agents, which can not only be used in pharmacological studies by biologists, but can also be used as medicine in smooth muscle relaxation, inhibiting platelet aggregation, regulating cardiac function, and cancer therapy.
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