Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio

Frank A. Dunand; Rachel S. Dickins; David Parker; André E. Merbach

doi:10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2

Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio

Frank A. Dunand, Rachel S. Dickins, David Parker, André E. Merbach^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

88 Citations (Scopus)

Abstract

¹H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu (dota-tetraamide) (H₂O)]³⁺ complexes. The direct ¹H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: k_ex²⁹⁸ = 9.4± 0.2 × 10³ s-1 for [Eu(dotam)(H₂O)]³⁺, 8.2 ± 0.2 × 10³ s^-1 for [Eu(dtma)(H₂O)]³⁺ and 11.2 ± 1.4 × 10³ s^-1 for [Eu(dotmam)-(H₂O)]³⁺; m: k_ex²⁹⁸ = 474 ± 130 × 103 s^-1 for [Eu(dotam)(H₂O]³⁺, 357 ± 92 × 10³S^-1 for [Eu(dtma)(H₂O)³⁺), and proceed through a dissociative mechanism (M isomers: ΔV‡ = + 4.9 cm³ mol^-1 for [Eu(dotam)(H₂O)]³⁺ and + 6.9 cm³ mol^-1 for [Eu(dtma)(H₂O)]³⁺). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by α-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential Gd^III-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

Original language	English
Pages (from-to)	5160-5167
Number of pages	8
Journal	Chemistry - A European Journal
Volume	7
Issue number	23
Early online date	22 Nov 2001
DOIs	https://doi.org/10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2
Publication status	Published - 3 Dec 2001

User-Defined Keywords

Contrast agents
Lanthanides
Ligand design
Magnetic resonance imaging
Solution dynamics
Water exchange

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10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2

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@article{0294061304134a3e97d97b75e1c6f4d7,

title = "Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio",

abstract = "1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu (dota-tetraamide) (H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: kex298 = 9.4± 0.2 × 103 s-1 for [Eu(dotam)(H2O)]3+, 8.2 ± 0.2 × 103 s-1 for [Eu(dtma)(H2O)]3+ and 11.2 ± 1.4 × 103 s-1 for [Eu(dotmam)-(H2O)]3+; m: kex298 = 474 ± 130 × 103 s-1 for [Eu(dotam)(H2O]3+, 357 ± 92 × 103S-1 for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: ΔV‡ = + 4.9 cm3 mol-1 for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol-1 for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by α-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential GdIII-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.",

keywords = "Contrast agents, Lanthanides, Ligand design, Magnetic resonance imaging, Solution dynamics, Water exchange",

author = "Dunand, {Frank A.} and Dickins, {Rachel S.} and David Parker and Merbach, {Andr{\'e} E.}",

note = "Publisher Copyright: {\textcopyright} 2001 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany",

year = "2001",

month = dec,

day = "3",

doi = "10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2",

language = "English",

volume = "7",

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journal = "Chemistry - A European Journal",

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publisher = "John Wiley & Sons Ltd",

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T1 - Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio

AU - Dunand, Frank A.

AU - Dickins, Rachel S.

AU - Parker, David

AU - Merbach, André E.

PY - 2001/12/3

Y1 - 2001/12/3

N2 - 1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu (dota-tetraamide) (H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: kex298 = 9.4± 0.2 × 103 s-1 for [Eu(dotam)(H2O)]3+, 8.2 ± 0.2 × 103 s-1 for [Eu(dtma)(H2O)]3+ and 11.2 ± 1.4 × 103 s-1 for [Eu(dotmam)-(H2O)]3+; m: kex298 = 474 ± 130 × 103 s-1 for [Eu(dotam)(H2O]3+, 357 ± 92 × 103S-1 for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: ΔV‡ = + 4.9 cm3 mol-1 for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol-1 for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by α-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential GdIII-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

AB - 1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu (dota-tetraamide) (H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: kex298 = 9.4± 0.2 × 103 s-1 for [Eu(dotam)(H2O)]3+, 8.2 ± 0.2 × 103 s-1 for [Eu(dtma)(H2O)]3+ and 11.2 ± 1.4 × 103 s-1 for [Eu(dotmam)-(H2O)]3+; m: kex298 = 474 ± 130 × 103 s-1 for [Eu(dotam)(H2O]3+, 357 ± 92 × 103S-1 for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: ΔV‡ = + 4.9 cm3 mol-1 for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol-1 for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by α-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential GdIII-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

KW - Contrast agents

KW - Lanthanides

KW - Ligand design

KW - Magnetic resonance imaging

KW - Solution dynamics

KW - Water exchange

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U2 - 10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2

DO - 10.1002/1521-3765(20011203)7:23<5160::AID-CHEM5160>3.0.CO;2-2

M3 - Journal article

C2 - 11775689

AN - SCOPUS:0035802940

SN - 0947-6539

VL - 7

SP - 5160

EP - 5167

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 23

ER -

Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio

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