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

Angew Chem Int Ed Engl. 2022 May 23;61(22):e202201211. doi: 10.1002/anie.202201211. Epub 2022 Mar 29.

Abstract

Despite its prevalence in the environment, the chemistry of the Ti4+ ion has long been relegated to organic solutions or hydrolyzed TiO2 polymorphs. 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 THPMe respectively, were assessed for chelation of the 45 Ti 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 [45 Ti]Ti-TREN-CAM was found to have remarkable stability in vivo.

Keywords: Chelates; Coordination Chemistry; Hydrolysis; Radiochemistry; Titanium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Chelating Agents
  • Hydrolysis
  • Organometallic Compounds* / chemistry
  • Titanium* / chemistry
  • Water / chemistry

Substances

  • Chelating Agents
  • Organometallic Compounds
  • Water
  • Titanium