Reactive oxygen species are integral to many physiological processes. Although their roles are still being elucidated, they seem to be linked to a variety of disorders and may represent promising drug targets. Mimics of superoxide dismutases, which catalyse the decomposition of O2•− to H2O2 and O2, have traditionally used redox-active metals, which are toxic outside of a tightly coordinating ligand. Purely organic antioxidants have also been investigated but generally require stoichiometric, rather than catalytic, doses. Here, we show that a complex of the redox-inactive metal zinc(ii) with a hexadentate ligand containing a redox-active quinol can catalytically degrade superoxide, as demonstrated by both reactivity assays and stopped-flow kinetics studies of direct reactions with O2•− and the zinc(ii) complex. The observed superoxide dismutase catalysis has an important advantage over previously reported work in that it is hastened, rather than impeded, by the presence of phosphate, the concentration of which is high under physiological conditions.
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Crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre, under deposition nos. CCDC 1830122 ([ZnH2qtp1](MeCN)](OTf)2, 3), 1830123 ([Zn(H2qtp1)(OTf)](OTf), 2) and 1830124 (H2qtp1). Copies of the data can be obtained free of charge from www.ccdc.cam.ac.uk/structures/. All other data supporting the findings of this study are available within the Article and its Supplementary Information, and/or from the corresponding authors upon reasonable request
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The authors thank C. Kreitzer and R. Boothe for technical assistance. T. Hutchinson collected the 19F NMR and IR data for 2. E. Hardy assisted with solution of the crystal structure of H2qtp1. The authors thank Auburn University, the Auburn University Research Initiative in Cancer, and the National Science Foundation (NSF-CHE-1662875) for financial support. NSF EPSCoR/AU-CMB summer fellowships provided additional support to M.Y. and M.B.W.
The authors declare no competing interests.
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Experimental section, Supplementary Figures 1–20, SupplementaryTable 1
CIF for ligand H2qtp1; CCDC reference: 1830124
Structure-factor file for ligand H2qtp1; CCDC reference: 1830124
CIF for compound 2; CCDC reference: 1830123
CIF for compound 3; CCDC reference: 1830122
Structure-factor file for compound 3; CCDC reference: 1830122
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Ward, M.B., Scheitler, A., Yu, M. et al. Superoxide dismutase activity enabled by a redox-active ligand rather than metal. Nature Chem 10, 1207–1212 (2018). https://doi.org/10.1038/s41557-018-0137-1
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