O2-binding properties of double-sided porphinatoiron(II)s with polar substituents and their human serum albumin hybrids

Article abstract of DOI:10.1246/bcsj.74.1695

Double-sided porphinatoiron(II)s with polar substituents [R; hydroxy (FeDP(OH)), methoxy (FeDP(OMe)), and acetoxy (FeDP(OAc))] on the 2,2-dimethylpropanoyloxy-fence groups have been synthesized. FeDP(OMe) and FeDP(OAc) formed five-N-coordinated high-spin Fe²⁺ complexes with an intramolecularly bound axial imidazole in toluene (or CH₂Cl₂) under an N₂ atmosphere. Upon the addition of O₂, they produced stable O₂ adducts at 25 °C; their half-lives in water-saturated toluene (50-77 h) are 2-3 fold longer compared to that of the single-face encumbered porphinatoiron(II) (FeP). Their O₂-binding parameters are almost identical to that of FeDP(H), which has nonpolar substituents on the fences. In contrast, FeDP(OH) showed a significantly low O₂-binding affinity and was immediately oxidized to the Fe³⁺ state after contact with bubbling O₂ gas. The incorporation of these FeDPs into the human serum albumin (HSA) provided artificial hemoproteins, which can reversibly bind and release O₂ under physiological conditions (in aqueous media, pH 7.3, 37 °C) like hemoglobin and myoglobin. The half-life of the dioxygenated HSA-FeDP(H) reached 5 h (37 °C). This corresponded to a 2.5-fold increase compared to that of HSA-FeP. The time dependences of the absorption changes accompanying the O_2- and CO-rebindings to the HSA-FeDPs after laser flash photolysis were composed of two phases. These observations indicate that the recombination of O₂ and CO to the central Fe²⁺ ion is affected by the microenvironments around the FeDPs in the HSA structure, e.g. a steric hindrance of the amino acid residue and a difference in polarity. Furthermore, FeDP(H) incorporated into HSA showed a high stability against H₂O₂.