Formation of titanium(IV) transferrin by reaction of human serum apotransferrin with titanium complexes

The reaction of human serum apotransferrin with titanium(IV) citrate under physiological conditions results in the formation of a specific bis-titanium(IV) transferrin adduct (Ti₂Tf hereafter) with two titanium(IV) ions loaded at the iron binding sites. The same specific Ti₂Tf complex is formed by reacting apotransferrin with titanium(III) chloride and exposing the sample to air. The derivative thus obtained was characterized by spectroscopic techniques, including absorption, UV difference, circular dichroism and ¹³C NMR spectroscopies, and shown to be stable within the pH range 5.5–9.0. Surprisingly, the reaction of apoTf with titanium(IV) nitrilotriacetate (NTA) does not lead to formation of appreciable amounts of Ti₂Tf, even after long incubation times, although some weak interactions of Ti(IV)NTA with apoTf are spectroscopically detected. Implications of the present results for a role of transferrin in the uptake, transport and delivery of soluble titanium(IV) compounds under physiological conditions are discussed.