Site-Differentiated MnFe Complex Reproducing the Selective Assembly of Biological Heterobimetallic Mn/Fe Cofactors.

Class Ic ribonucleotide reductases (RNRIc) and R2-like ligand-binding oxidases (R2lox) are known to contain heterobimetallic MnFe cofactors. How these enzymes assemble MnFe cofactors has been a long-standing puzzle due to the weaker binding affinity of Mn versus Fe. In addition, the heterobimetallic selectivity of RNRIc and R2lox has yet to be reproduced with coordination complexes, leading to the hypothesis that RNRIc and R2lox overcome the thermodynamic preference for coordination of Fe over Mn with their carefully constructed three-dimensional protein structures. Herein, we report the selective formation of a heterobimetallic MnFe complex accomplished in the absence of a protein scaffold. Treatment of the ligand PyDMcT () with equimolar amounts of Fe and Mn along with two equivalents of acetate (OAc) affords [MnFe (OAc)(OTf)] () in 80% yield, while the diiron complex [FeFe(OAc)(OTf)] () is produced in only 8% yield. The formation of is favored regardless of the order of addition of Fe and Mn sources. X-ray diffraction (XRD) of single crystals of reveals an unsymmetrically coordinated carboxylate ligand─a primary coordination sphere feature shared by both RNRIc and R2lox that differentiates the two metal binding sites. Anomalous XRD studies confirm that exhibits the same site selectivity as R2lox and RNRIc, with the Fe (d) center preferentially occupying the distorted octahedral site. We conclude that the successful assembly of originates from (1) Fe-deficient conditions, (2) site differentiation, and (3) the inability of ligand to house a dimanganese complex.