Water-soluble titanocene complexes with sulfur-containing amino acids: synthesis, spectroscopic, electrochemical and Ti(IV)-transferrin interaction studies

Three new water soluble titanocene-amino acid complexes have been synthesized via the reaction of Cp(2)TiCl(2) and two equivalents of amino acid (L) in methanol, affording [Cp(2)TiL(2)]Cl(2), L = L-cysteine (2), D-penicillamine (3) and L-methionine (4). These complexes have been characterized by (1)H, IR and UV-Vis spectroscopies, elemental analysis and cyclic voltammetry. Kinetic studies of ligand hydrolysis have been monitored at low pH using UV-Vis and (1)H NMR spectroscopies to assess their stability in aqueous solution. At low pH, amino acid ligands are lost one order of magnitude faster than cyclopentadienyl. However, at physiological pH, in Tris buffer solution, the complexes decompose rapidly to form an insoluble titanium compound. The affinity of these complexes to apo-transferrin was also investigated to elucidate how the ancillary amino acid ligands affect the titanium intake by apo-transferrin.