Synergistic anion-directed coordination of ferric and cupric ions to bovine serum transferrin - An inorganic perspective

A series of new iron(III) and copper(II) complexes of bovine serum transferrin (BTf), with carbonate and/or oxalate as the synergistic anion, are presented. The complexes [Fe₂(CO₃)₂BTf], [Fe₂(C₂O₄)₂BTf], [Cu ₂(CO₃)₂BTf] and [Cu(C₂O ₄)BTf] were prepared by standard titrimetric techniques. The oxalate derivatives were also obtained from the corresponding carbonate complexes by anion-displacement. The site-preference of the transition metal-oxalate synergism has facilitated the preparation and isolation of the mononuclear complex [Cu(C₂O₄)BTf], the mixed-anion complexes [Cu ₂(CO₃)(C₂O₄)BTf] and [Fe ₂(CO₃)(C₂O₄)BTf] and the mixed-metal complex [FeCu(C₂O₄)₂BTf]. The sensitivity of electron paramagnetic resonance (EPR) spectroscopy to the nature of the synergistic anions at the specific-binding sites of the transferrins has made this physical technique particularly indispensable to this study. None of the other members of the transferrin family of proteins has ever been demonstrated to bind the ferric and cupric ions one after the other, each occupying a separate specific-binding site of the same transferrin molecule, as a response to the coordination restrictions imposed by the oxalate ion. The bathochromic shift of the visible p_π-d_π* CT band for iron(III)-BTf and the hypsochromic shift of the p_π-d _σ* CT band for copper(II)-BTf, on replacing carbonate by oxalate as the associated anion, are consistent with the relative positions of these anionic ligands in the spectrochemical series and the nature of the d-type acceptor orbitals involved in the CT transitions. The binding and spectroscopic properties of bovine serum transferrin - a serum transferrin - very nearly mirror those of human serum transferrin, but differ significantly from those of human lactoferrin.