Class Ib Ribonucleotide Reductases: Activation of a Peroxido-Mn II Mn III to Generate a Reactive Oxo-Mn III Mn IV Oxidant.

In the postulated catalytic cycle of class Ib Mn 2 ribonucleotide reductases (RNRs), a Mn II 2 core is suggested to react with superoxide (O 2 ·- ) to generate peroxido-Mn II Mn III and oxo-Mn III Mn IV entities prior to proton-coupled electron transfer (PCET) oxidation of tyrosine. There is limited experimental support for this mechanism. We demonstrate that [Mn II 2 (BPMP)(OAc) 2 ](ClO 4 ) ( 1 , HBPMP = 2,6-bis[(bis(2 pyridylmethyl)amino)methyl]-4-methylphenol) was converted to peroxido-Mn II Mn III ( 2 ) in the presence of superoxide anion that converted to (μ-O)(μ-OH)Mn III Mn IV ( 3 ) via the addition of an H + -donor ( p- TsOH) or (μ-O) 2 Mn III Mn IV ( 4 ) upon warming to room temperature. The physical properties of 3 and 4 were probed using UV-vis, EPR, X-ray absorption, and IR spectroscopies and mass spectrometry. Compounds 3 and 4 were capable of phenol oxidation to yield a phenoxyl radical via a concerted PCET oxidation, supporting the proposed mechanism of tyrosyl radical cofactor generation in RNRs. The synthetic models demonstrate that the postulated O 2 /Mn 2 /tyrosine activation mechanism in class Ib Mn 2 RNRs is plausible and provides spectral insights into intermediates currently elusive in the native enzyme.