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Unsymmetric bimetallic centres in metalloproteins and synthetic models

Nature Reviews Chemistry (2025)Cite this article

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Abstract

Many biological bimetallic active sites exhibit unsymmetric coordination environments, allowing the two metal centres to perform distinct catalytic roles. By contrast, most synthetic homogeneous catalysts rely on symmetric ligand frameworks for ease of synthesis. This represents a considerable divergence between natural and synthetic catalysts, leaving the functional importance of unsymmetric arrangement largely underexplored. In this Review, we highlight biological examples of unsymmetric bimetallic centres and their roles in catalysis. We examine how the inherent lack of symmetry — achieved through ligand differentiation or heterobimetallic design — has been used to mimic nature’s bimetallic sites. We also discuss recent advances that show how an unsymmetric environment can lower the barriers of bond activation and outline current challenges in probing the function of unsymmetric features, along with strategies to overcome them.

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Fig. 1: Examples and classification of unsymmetric bimetallic centres.
Fig. 2: Comparison of O2 activation at symmetric versus unsymmetric bimetallic sites.
Fig. 3: Structures of unsymmetric bimetallic sites and the proposed reaction mechanisms.
Fig. 4: Examples of heterobimetallic cofactors.
Fig. 5: Examples of unsymmetric di-Cu complexes.
Fig. 6: Examples of unsymmetric di-Cu complexes.
Fig. 7: Examples of unsymmetric di-Fe complexes.
Fig. 8: Examples of unsymmetric di-Ni and heterobimetallic FeMn complexes.

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Acknowledgements

This work was supported by the National Science Foundation under Grant No. CHE-2246440.

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    Saikat Mondal, Preston Myers & Shiyu Zhang

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Mondal, S., Myers, P. & Zhang, S. Unsymmetric bimetallic centres in metalloproteins and synthetic models. Nat Rev Chem (2025). https://doi.org/10.1038/s41570-025-00781-9

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