A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes.

Despite its prevalence in the environment, the chemistry of the Ti 4+ ion has long been relegated to organic solutions or hydrolyzed TiO 2 polymorphs. A knowledge gap in stabilizing molecular Ti 4+ species in aqueous environments has prevented the use of this ion for various applications such as radioimaging, design of water-compatible metal-organic frameworks (MOFs), and aqueous-phase catalysis applications. Herein, we show a thorough thermodynamic screening of bidentate chelators with Ti 4+ in aqueous solution, as well as computational and structural analyses of key compounds. In addition, the hexadentate analogues of catechol (benzene-1,2-diol) and deferiprone (3-hydroxy-1,2-dimethyl-4(1H)-pyridone), TREN-CAM and THP Me respectively, were assessed for chelation of the 45 Ti isotope (t 1/2 =3.08 h, β + =85 %, E β+ =439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit-formulation, and [ 45 Ti]Ti-TREN-CAM was found to have remarkable stability in vivo.