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

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

Chemistry (Twin Cities)

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	e202201211
Journal	Angewandte Chemie - International Edition
Volume	61
Issue number	22
DOIs	https://doi.org/10.1002/anie.202201211
State	Published - 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.

Keywords

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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10.1002/anie.202201211

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Koller, A. J., Saini, S., Chaple, I. F., Joaqui-Joaqui, M. A., Paterson, B. M., Ma, M. T., Blower, P. J., Pierre, V. C., Robinson, J. R., Lapi, S. E., & Boros, E. (2022). A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes. Angewandte Chemie - International Edition, 61(22), [e202201211]. https://doi.org/10.1002/anie.202201211

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

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 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.",

keywords = "Chelates, Coordination Chemistry, Hydrolysis, Radiochemistry, Titanium, Organometallic Compounds/chemistry, Catalysis, Titanium/chemistry, Water/chemistry, Chelating Agents",

author = "Koller, {Angus J.} and Shefali Saini and Chaple, {Ivis F.} and Joaqui-Joaqui, {M. Andrey} and Paterson, {Brett M.} and Ma, {Michelle T.} and Blower, {Philip J.} and Pierre, {Val{\'e}rie C.} and Robinson, {Jerome R.} and Lapi, {Suzanne E.} and Eszter Boros",

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: {\textcopyright} 2022 Wiley-VCH GmbH.",

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doi = "10.1002/anie.202201211",

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T1 - A General Design Strategy Enabling the Synthesis of Hydrolysis-Resistant, Water-Stable Titanium(IV) Complexes

AU - Koller, Angus J.

AU - Saini, Shefali

AU - Chaple, Ivis F.

AU - Joaqui-Joaqui, M. Andrey

AU - Paterson, Brett M.

AU - Ma, Michelle T.

AU - Blower, Philip J.

AU - Pierre, Valérie C.

AU - Robinson, Jerome R.

AU - Lapi, Suzanne E.

AU - Boros, Eszter

N1 - 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.

PY - 2022/5/23

Y1 - 2022/5/23

N2 - 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.

AB - 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.

KW - Chelates

KW - Coordination Chemistry

KW - Hydrolysis

KW - Radiochemistry

KW - Titanium

KW - Organometallic Compounds/chemistry

KW - Catalysis

KW - Titanium/chemistry

KW - Water/chemistry

KW - Chelating Agents

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DO - 10.1002/anie.202201211

M3 - Article

C2 - 35263017

AN - SCOPUS:85127291842

SN - 1433-7851

VL - 61

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 22

M1 - e202201211

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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