Site-Differentiated Mn II Fe II 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 Mn II Fe II cofactors. How these enzymes assemble Mn II Fe II cofactors has been a long-standing puzzle due to the weaker binding affinity of Mn II versus Fe II . 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 II over Mn II with their carefully constructed three-dimensional protein structures. Herein, we report the selective formation of a heterobimetallic Mn II Fe II complex accomplished in the absence of a protein scaffold. Treatment of the ligand Py 4 DMcT ( L ) with equimolar amounts of Fe II and Mn II along with two equivalents of acetate (OAc) affords [ L Mn II Fe II (OAc) 2 (OTf)] + ( Mn II Fe II ) in 80% yield, while the diiron complex [ L Fe II Fe II (OAc) 2 (OTf)] + ( Fe II Fe II ) is produced in only 8% yield. The formation of Mn II Fe II is favored regardless of the order of addition of Fe II and Mn II sources. X-ray diffraction (XRD) of single crystals of Mn II Fe II 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 Mn II Fe II exhibits the same site selectivity as R2lox and RNRIc, with the Fe II (d 6 ) center preferentially occupying the distorted octahedral site. We conclude that the successful assembly of Mn II Fe II originates from (1) Fe-deficient conditions, (2) site differentiation, and (3) the inability of ligand L to house a dimanganese complex.