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The first direct syntheses, structural characterizations, and reactivity studies of multinuclear iron–phenyl species formed upon reaction of Fe(acac)3 and PhMgBr in THF are described., The first direct syntheses, structural characterizations, and reactivity studies of iron–phenyl species formed upon reaction of Fe(acac)3 and PhMgBr in THF are presented. Reaction of Fe(acac)3 with 4 equiv. PhMgBr in THF leads to the formation of [FePh2(μ-Ph)]22– at –80 °C, which can be stabilized through the addition of N-methylpyrrolidone. Alternatively, at –30 °C this reaction leads to the formation of the tetranuclear iron–phenyl cluster, Fe4(μ-Ph)6(THF)4. Further synthetic studies demonstrate that analogous tetranuclear iron clusters can be formed with both 4-F-PhMgBr and p-tolylMgBr, illustrating the generality of this structural motif for reactions of simple ferric salts and aryl Grignard reagents in THF. Additional studies isolate and define key iron species involved in the synthetic pathway leading to the formation of the tetranuclear iron–aryl species. While reaction studies demonstrate that [FePh2(μ-Ph)]22– is unreactive towards electrophile, Fe4(μ-Ph)6(THF)4 is found to rapidly react with bromocyclohexane to selectively form phenylcyclohexane. Based on this reactivity, a new catalytic reaction protocol has been developed that enables efficient cross-couplings using Fe4(μ-Ph)6(THF)4, circumventing the current need for additives such as TMEDA or supporting ligands to achieve effective cross-coupling of PhMgBr and a secondary alkyl halide.

Magnetic circular dichroism studies of Fe(ii) binding to human calprotectin demonstrate the nature of Fe(ii) coordination at two different Fe(ii)-binding sites and provide insight into how Ca(ii) modulates Fe(ii) coordination., Calprotectin (CP) is an abundant metal-chelating protein involved in host defense, and the ability of human CP to bind Fe(ii) in a calcium-dependent manner was recently discovered. In the present study, near-infrared magnetic circular dichroism spectroscopy is employed to investigate the nature of Fe(ii) coordination at the two transition-metal-binding sites of CP that are a His3Asp motif (site 1) and a His6 motif (site 2). Upon the addition of sub-stoichiometric Fe(ii), a six-coordinate (6C) Fe(ii) center associated with site 2 is preferentially formed in the presence of excess Ca(ii). This site exhibits an exceptionally large ligand field (10D q = 11 045 cm–1) for a non-heme Fe(ii) protein. Analysis of CP variants lacking residues of the His6 motif supports that CP coordinates Fe(ii) at site 2 by employing six His ligands. In the presence of greater than one equiv. of Fe(ii) or upon mutation of the His6 motif, the metal ion also binds at site 1 of CP to form a five-coordinate (5C) Fe(ii)–His3Asp motif that was previously unidentified in this system. Notably, the introduction of His-to-Ala mutations at the His6 motif results in a mixture of 6C (site 2) and 5C (site 1) signals in the presence of sub-stoichiometric Fe(ii). These results are consistent with a reduced Fe(ii)-binding affinity of site 2 as more weakly coordinating water-derived ligands complete the 6C site. In the absence of Ca(ii), both sites 1 and 2 are occupied upon addition of sub-stoichiometric Fe(ii), and a stronger ligand field is observed for the 5C site. These spectroscopic studies provide further evaluation of a unique non-heme Fe(ii)–His6 site for metalloproteins and support the notion that Ca(ii) ions influence the Fe(ii)-binding properties of CP.