Dinuclear heme and non-heme metal complexes as bioinspired catalysts for oxidation reactions

Abstract

Inspired by catalytic sites of cytochrome c oxidase (CcO) and nitric oxide reductase (NOR), a new series of dinuclear heme–non-heme complexes is described. The complexes are derived from the association between an iron(III)–protoporphyrin IX containing a covalently attached Gly-L-His-OMe residue to one propionic acid substituent (HMGH) and a metal complex with a tridentate amino-bis(benzimidazole) (BBH) ligand, mimicking the tris-histidine coordination of Fe_B and Cu_B in NOR and CcO, respectively. Besides the coordination of Fe^III and Cu^II with the BBH ligand, we also explored the role of “non-biomimetic” metals, such as Co^II, Mn^II, or Zn^II, in order to establish the priority among the ancillary metal ions in cooperating with the ferric heme and promoting its catalytic activity in oxidation reactions. pH-spectrophotometric titrations show that the presence of the non-heme metal decreases the pK_a of water-bound to hemin (pK_a = 8.4 ± 0.1), with a larger effect with iron(III), copper(II) and zinc(II) complexes (pK_a of 6.4 ± 0.1, 6.0 ± 0.1 and 6.5 ± 0.1, respectively), which suggests that an interaction with the non-heme metal center takes place also at a micromolar range. NMR spectra indicate that the interaction between hemin and the non-heme center is not strong enough to convert the high spin configuration of Fe^III–heme to low spin as observed for CcO and NOR enzymes. The dinuclear complex enhances the peroxidase-like activity of heme in kinetic studies performed at pH 5.5, 7.0 (using 3-(4-hydroxyphenyl)-propanoic acid as the substrate) and 9.0 (using o-phenylenediamine). In particular, the stronger effects are observed with Fe^III, Cu^II, and Co^II complexes, which increase the turnover rates of hemin throughout the pH range analyzed. At neutral and basic pH the K_M value decreases up to one fourth indicating a positive cooperation between HMGH and [M(BBH)]ⁿ⁺ in binding the substrates. Moreover, the presence of the non-heme center facilitates the binding of H₂O₂ and formation of high valent ˙PFe^IVO species. These data show that interaction between the two metal centers occurs with heme in several oxidation states.