Site-Differentiated MnIIFeII 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 MnIIFeII cofactors. How these enzymes assemble MnIIFeII cofactors has been a long-standing puzzle due to the weaker binding affinity of MnII versus FeII. 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 FeII over MnII with their carefully constructed three-dimensional protein structures. Herein, we report the selective formation of a heterobimetallic MnIIFeII complex accomplished in the absence of a protein scaffold. Treatment of the ligand Py4DMcT (L) with equimolar amounts of FeII and MnII along with two equivalents of acetate (OAc) affords [LMnIIFeII (OAc)2(OTf)]+ (MnIIFeII) in 80% yield, while the diiron complex [LFeIIFeII(OAc)2(OTf)]+ (FeIIFeII) is produced in only 8% yield. The formation of MnIIFeII is favored regardless of the order of addition of FeII and MnII sources. X-ray diffraction (XRD) of single crystals of MnIIFeII 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 MnIIFeII exhibits the same site selectivity as R2lox and RNRIc, with the FeII (d6) center preferentially occupying the distorted octahedral site. We conclude that the successful assembly of MnIIFeII originates from (1) Fe-deficient conditions, (2) site differentiation, and (3) the inability of ligand L to house a dimanganese complex.