Coordination Chemistry of an Emerging Group of Diazeniumdiolate Siderophores: Crystal Structures of M(III)-Gramibactin (M= Fe and Ga)

To overcome iron starvation, microorganisms often produce siderophores─chelators with high affinity and selectivity for Fe(III). The recent discovery of the siderophore gramibactin garnered significant interest, as it added the <i>C</i>-diazeniumdiolate as a new Fe(III)-binding group in siderophores. Gramibactin is a mixed ligand siderophore, comprised of two graminine residues harboring the diazeniumdiolate donors and a β-hydroxy-aspartate donor. Diazeniumdiolate siderophores have so far evaded crystallographic characterization and few structures of synthetic diazeniumdiolate complexes are reported. To address the gap in structural information, the complexes K[M(III)-gramibactin] (M = Fe and Ga) were prepared, crystallized and their structures solved by X-ray diffraction (XRD). The four Fe-O bond lengths in the two diazeniumdiolates are quite similar, ranging from 1.978 Å to 2.059 Å, indicating an equal contribution in bonding. In contrast, the differing Fe-O bond lengths in β-hydroxy-aspartate reflect the relative donor strengths of the carboxylate (1.997 Å) and alkoxide (1.902 Å) groups. Gramibactin coordinates Fe(III) in a Δ-configured distorted octahedral geometry. The diamagnetic nature of Ga(III) is often leveraged in NMR studies to infer the solution structure of the corresponding Fe(III)-siderophores, which are assumed to be identical. The structural similarity of Ga(III)- and Fe(III)-gramibactin is striking and represents the first crystallographic verification of the assumed isostructural relationship between a Ga(III)- and an Fe(III)-siderophore. By providing concrete evidence, this study promotes Ga(III) as a reliable proxy for Fe(III) in siderophore complexes, with implications for solution structure determination of siderophores and design of Ga(III)-siderophore-based theranostics.