A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity

► Mn porphyrin-based SOD mimic, MnTnHex-2-PyP5+, was optimized to reduce its toxicity. ► Introduction of oxygen atoms into all 4 hexyl chains gave rise to the superb SOD mimic MnTnBuOE-2-PyP5+. ► Positioning of oxygen atoms deep within hexyl chains preserved the lipophilic character of MnTnHex-2-PyP5+. ► MnTnBuOE-2-PyP5+ is twice more potent SOD mimic, but few-fold less toxic, than MnTnHex-2-PyP5+.