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

doi:10.1002/anie.202201211

Original language	English
Article number	e202201211
Journal	Angewandte Chemie - International Edition
Volume	61
Issue number	22
DOIs	https://doi.org/10.1002/anie.202201211
Accepted/In press	2022
Published	23 May 2022
Additional links	Link to publication in Scopus

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 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)3][ClO4]H2O. 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. Publisher Copyright: © 2022 Wiley-VCH GmbH.

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 THP^Me respectively, were assessed for chelation of the ⁴⁵Ti 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 [⁴⁵Ti]Ti-TREN-CAM was found to have remarkable stability in vivo.

King's College London

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