C−H Activation by a Mononuclear Manganese(III) Hydroxide Complex: Synthesis and Characterization of a Manganese-Lipoxygenase Mimic?

Lipoxygenases are mononuclear non-heme metalloenzymes that regio- and stereospecifically
convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is
generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an
active metal(III)-hydroxide species to give a metal(II)-water species and an organic radical. All known plant
and animal lipoxygenases contain iron as the active metal; recently, however, manganese was found to
be the active metal in a fungal lipoxygenase. Reported here are the synthesis and characterization of a
mononuclear Mn(III) complex, [MnIII(PY5)(OH)](CF3SO3)2 (PY5 = 2,6-bis(bis(2-pyridyl)methoxymethane)pyridine), that reacts with hydrocarbon substrates in a manner most consistent with hydrogen atom
abstraction and provides chemical precedence for the proposed reaction mechanism. The neutral penta-pyridyl ligation of PY5 endows a strong Lewis acidic character to the metal center allowing the Mn(III)
compound to perform this oxidation chemistry. Thermodynamic analysis of [MnIII(PY5)(OH)]2+ and the
reduced product, [MnII(PY5)(H2O)]2+, estimates the strength of the O−H bond in the metal-bound water in
the Mn(II) complex to be 82 (±2) kcal mol-1, slightly less than that of the O−H bond in the related reduced
iron complex, [FeII(PY5)(MeOH)]2+. [MnIII(PY5)(OH)]2+ reacts with hydrocarbon substrates at rates
comparable to those of the analogous [FeIII(PY5)(OMe)]2+ at 323 K. The crystal structure of [MnIII(PY5)(OH)]2+ displays Jahn−Teller distortions that are absent in [MnII(PY5)(H2O)]2+, notably a compression along
the Mn(III)−OH axis. Consequently, a large internal structural reorganization is anticipated for hydrogen
atom transfer, which may be correlated to the lessened dependence of the rate of substrate oxidation on
the substrate bond dissociation energy as compared to other metal complexes. The results presented
here suggest that manganese is a viable metal for lipoxygenase activity and that, with similar coordination
spheres, iron and manganese can oxidize substrates through a similar mechanism.