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 T. Ma, Philip J. Blower, Valérie C. Pierre, Jerome R. Robinson, Suzanne E. Lapi, Eszter Boros

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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 45Ti 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.

Original languageEnglish (US)
Article numbere202201211
JournalAngewandte Chemie - International Edition
Issue number22
StatePublished - May 23 2022

Bibliographical note

Funding Information:
J.R.R. and E.B. thank Rigaku Americas for the use of the Synergy S and for Dr. Pierre LeMeguerre for collecting the single crystal data for [Ti(def)][ClO]HO. This research was funded in part by the 2019 ERF SNMMI Predoctoral Molecular Imaging Scholar program (IFC). Animal experiments were supported through the UAB Comprehensive Cancer Center P30CA013148. Additional support for this project came from the Department of Radiology at the University of Alabama at Birmingham and the UAB cyclotron facility. Stony Brook University and the Gordon and Betty Moore Foundation (E. B.) are thanked for generous financial support of this work. 3 4 2

Publisher Copyright:
© 2022 Wiley-VCH GmbH.


  • Chelates
  • Coordination Chemistry
  • Hydrolysis
  • Radiochemistry
  • Titanium
  • Organometallic Compounds/chemistry
  • Catalysis
  • Titanium/chemistry
  • Water/chemistry
  • Chelating Agents

PubMed: MeSH publication types

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


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