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

Abstract

AbstractDespite its prevalence in the environment, the chemistry of the Ti4+ion has long been relegated to organic solutions or hydrolyzed TiO2polymorphs. A knowledge gap in stabilizing molecular Ti4+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 Ti4+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 THPMerespectively, were assessed for chelation of the45Ti isotope (t1/2=3.08 h, β+=85 %, Eβ+=439 keV) towards positron emission tomography (PET) imaging applications. Both were found to have excellent capacity for kit‐formulation, and [45Ti]Ti‐TREN‐CAM was found to have remarkable stability in vivo.