A General Design Strategy Enabling the Synthesis of Hydrolysis‐Resistant, Water‐Stable Titanium(IV) Complexes
Angus J. Koller, Shefali Saini, Ivis F. Chaple, M. Andrey Joaqui‐Joaqui, Brett M. Paterson, Michelle Ma, Philip J. Blower, Valérie C. Pierre, Jerome R. Robinson, Suzanne E. Lapi, Eszter Boros
Abstract
Abstract 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(1 H )‐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.