Manganese(III) Complexes of Bis-Hydroxyphenyldipyrromethenes are Potent Orally Active Peroxynitrite Scavengers

摘要

We report a new series of bis-cyclohexano-fused Mn(III) complexes of bis-hydroxyphenyl-dipyrromethenes (DIPYs) >4a–c as potent and orally active peroxynitrite scavengers. Complexes >4a–c have been shown to reduce peroxynitrite through a 2-electron mechanism thereby forming the corresponding Mn(V)O species, which have been characterized by UV, NMR, and LCMS methods. Mn(III) complex >4b and its strained BODIPY analogue >9b have been analyzed by x-ray crystallography. Finally, complex >4a has been shown to be an orally active and potent analgesic in a model carrageenan-induced hyperalgesia known to be driven by the overproduction of peroxynitrite.