Mechanistic Insights into Superoxide Dismutation Driven by Dinuclear Manganese Complexes: The Role of the Mn2-Core

The dinuclear Mn-2(II,II)L-2-core (HL = 2-{[[di(2-pyridyl)methyl](methyl)amino]-methyl}phenol)has been recently reported to be the most active dual superoxide dismutase(SOD) and catalase (CAT) functional analogue, enabling cascade detoxificationof the superoxide radical anion. Here, we investigated the mechanismof catalytic O-2 (center dot-) decompositionby two stereoisomers with the Mn-2(II,II)L-2-core, Mn ( 2 ) L ( 2 ) Ac and Mn ( 2 ) L ( 2 ), in order to (i) preciselydetermine the catalytic SOD activity of the complexes, (ii) characterizethe key intermediates involved in the dismutation process, and (iii)discriminate between single- and di-Mn center catalysis in relationto the configuration of the Mn-2-core. The conclusions drawnfrom low-temperature mass spectrometry, stopped-flow kinetics, cyclicvoltammetry, water exchange O-17 nuclear magnetic resonance(NMR), and electron paramagnetic resonance (EPR) analyses were supportedby the structural characterization and quantum chemical analysis ofthe proposed reaction intermediates. This study allows us to determine k (cat) for Mn ( 2 ) L ( 2 ) Ac and Mn ( 2 ) L ( 2 ) (4.6 x 10(7) and 2.2 x 10(7) M-1 s(-1), respectively, in 3-(N-morpholino)propanesulfonic acid (MOPS) at pH = 7.4) anddetect the key intermediates involved in the catalytic cycle drivenby these Mn-2-SOD mimics, highlighting the formation ofa side-on eta(2)-Mn-2(III,II)-peroxo,as an initial intermediate. The effects of the Mn-2(II,II)-coreconfiguration on the SOD activity were discussed.

Automated summary

The most active dual superoxide dismutase (SOD) and catalase (CAT) functional analogue, the dinuclear Mn-2(II,II)L-2-core, was investigated for its catalytic O-2 (center dot-) decomposition mechanism. Two stereoisomers were studied to determine their SOD activity, characterize the intermediates involved, and differentiate between single- and di-Mn center catalysis. Structural characterization, quantum chemical analysis, and various analytical techniques supported the conclusions drawn from this study. The effects of the Mn-2(II,II)-core configuration on the SOD activity were discussed.