Preparation of Liposomes Surface-Loaded with Cationic Manganese Porphyrins as SOD Mimics

A water-soluble cationic 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphinatomanganese(III) ion (MnT4MPyP) and water-insoluble 5,10,15,20-tetrakis(N-3-furyl)porphinatomanganese(III) ion (MnT3FuP) were prepared and ion-complexed with an anionic phospholipid membrane to enhance the circulation persistence of the porphyrin complexes in vivo. Fluorescence spectra and fluorescence depolarization experiments indicated MnT3FuP to be situated within the hydrophobic interior of the vesicle composed of the phospholipid membrane, while MnT4MPyP was anchored to the membrane by lipophilic tails with the metalloporphyrin head-group located on the interface between the membrance and aqueous solvent. SOD activity was determined by stopped-flow analysis and cytochrome c assay, which allowed the determination of IC₅₀ and k_cat values for the reaction of the metalloporphyrins with superoxide anion radical (O₂^-·). Sodium stearate-linked MnT4MPyP was the most effective catalyst as an SOD mimic to decompose O₂^-· at a second-order rate constant of 1.9 × 10⁷ M^-1s^-1 in dimyristoylphosphatidylcholine (DMPC) liposomes. SOD activity of MnT3FuP was less than that of MnT4MPyP.