Source: Dissertation Abstracts International, Volume: 73-05, Section: B, page: .

Adviser: Ann Valentine.

Under the present common biological conditions, that is, in aerobic aqueous solution at circumneutral pH, titanium predominantly exists in the Ti(IV) oxidation state. The speciation of Ti(IV) in biological systems is assumed to be dominated by hydrolysis products with very low aqueous solubility. The biological availability of an element is a function of its solubility in water; therefore, titanium is generally considered to be a biologically inert element. The physical properties of the crystalline final hydrolysis product of Ti(IV), titanium dioxide (TiO2), make it useful as a white pigment and as a photocatalyst. The assumption of its biological inertness along with its useful properties have been the driving forces in the ever-increasing production and use of titanium dioxide materials, which can impact the levels and speciation of titanium in the environment.

There are, however, several lines of evidence that indicate that titanium may be biologically active. For example, certain titanium complexes have anti-cancer activity. Driven by these observations and by the chemical similarities between Ti(IV) and the biologically-relevant, well-studied, hydrolysis-prone metal ion Fe(III), this work was carried out to elucidate the fundamental aqueous coordination chemistry and photochemistry of titanium with biological molecules in an effort to better understand the role of titanium in biology. Evaluation of the literature shows that hydrolysis species of Ti(IV) are surprisingly soluble in water even in the absence of complexing ligands, and even higher concentrations of Ti(IV) are supported in aqueous solution in the presence of complexing ligands.

The experiments presented here demonstrated that Ti(IV) is protected from hydrolysis and stabilized in aqueous solution by complexation with members of a class of biological molecules known as the siderophores. Siderophores are low molecular weight Fe(III)-complexing molecules that are synthesized and exported under low-available-iron conditions by certain organisms, including plants, fungi, yeast, algae, bacteria, and archaea, to solubilize and sequester Fe(III) from the environment.

Specifically, the interactions of titanium and the trishydroxamic acid siderophore desferrioxamine B, the mixed alpha-hydroxy carboxylic acid/bishydroxamic acid siderophore aerobactin, and the alpha-hydroxy carboxylic acid siderophore citric acid were studied under biologically relevant conditions. In addition to the ability of siderophores to support high concentrations of Ti(IV) in aqueous solution (up to 0.6 mM Ti(IV) was observed), three additional modes of reactivity of aqueous Ti(IV)-siderophore complexes were observed. First, the aqueous solubility of both the anatase and rutile crystalline polymorphs of titanium dioxide was significantly increased in the presence of desferrioxamine B. Second, irradiation of the alpha-hydroxy carboxylic acid-to-Ti(IV) charge transfer bands of aqueous complexes of Ti(IV) aerobactin and Ti(IV) citrate, which absorb wavelengths of light that correspond to UVB sunlight, gave oxidative decarboxylation of the complexing molecules and concomitant reduction of Ti(IV) to Ti(III). Third, when Ti(III) was generated in this way from Ti(IV)-bound aerobactin, Ti(III) reduced one of the hydroxamic acid functionalities of the decarboxylated aerobactin to an amide. When Ti(III) was generated in this way from Ti(IV) citrate in the presence of desferrioxamine B, it similarly reduced one of the hydroxamic acids of desferrioxamine B to an amide.

This work adds to the fundamental understanding of the aqueous coordination chemistry and photochemistry of titanium, and the results presented here have implications for the speciation and the chemical reactivity of dissolved titanium in the surface waters of the ocean. Perhaps siderophores aid in the dissolution of Ti(IV) from Ti(IV) oxides deposited in the oceanic surface waters by aeolian deposition of dust. And perhaps the photochemical reactivity of Ti(IV) bound by alpha-hydroxy carboxylic acids leads to the destruction of the metal-binding ability of certain siderophores, thus affecting the biogeochemical cycling of iron in the photosynthetically active oceanic surface waters. Furthermore, a better fundamental understanding of the aqueous chemistry of titanium will aid in the development of titanium-based anti-cancer treatments.