Peroxynitrite is a powerful cytotoxic agent that is known to participate in deleterious nitration and oxidation reactions. Recent studies have classified peroxynitrite as a potent mediator to several disease states, including atherosclerosis, arthritis, amyotrophic lateral sclerosis, and Alzheimer's disease. There are no known natural scavengers of peroxynitrite that can effectively compete with its rapid formation and inhibit its fast reaction with cellular components. Thus, there exists a strong desire to develop non-toxic agents that can rapidly catalyze the decomposition of peroxynitrite for use as therapeutic drugs. Metalloporphyrin complexes have recently been shown to catalyze the decomposition of peroxynitrite. While they are among the most active catalysts reported for peroxynitrite decomposition, metalloporphyrins are short of ideal and do not effectively scavenge all available peroxynitrite. It is now proposed that bimetallic expanded prophyrin analogues be prepared and investigated for their reactivity towards peroxynitrite. The added structural flexibility of these larger ligands and the introduction of a second metal center are expected to significantly decrease activation barriers for peroxynitrite decomposition. The three types of expanded porphyrin ligands and several synthetic methodologies are proposed to produce new bimetallic complexes. Characterization and evaluation of new complexes by analytical and physical methods are also discussed.
| Liem, Edwin B; Lin, Chun-Ming; Suleman, Mohammad-Irfan et al. (2004) Anesthetic requirement is increased in redheads. Anesthesiology 101:279-83 |
