Molecular Dynamics of Gd(III) Complexes in Aqueous Solution by HF EPR

Borel, Alain; Helm, Lothar; Merbach, André E.

doi:10.1007/978-1-4757-4379-1_7

Cited by 7 publications

(5 citation statements)

References 52 publications

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“…When the 17 O NMR data are fitted to the Solomon−Bloembergen−Morgan theory, the parameters describing electron spin relaxation are also calculated. The recent development in the field of electronic relaxation of Gd III complexes showed that this model is not really adequate; however, due to its relative simplicity, it remains widely used . Therefore, we do not wish to interpret in details the parameters obtained in our fit.…”

Section: Resultsmentioning

confidence: 99%

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

et al. 2005

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Chiral, bifunctional poly(amino carboxylate) ligands are commonly used for the synthesis of macromolecular, Gd(III)-based MRI contrast agents, prepared in the objective of increasing relaxivity or delivering the paramagnetic Gd(III) to a specific site (targeting). Complex formation with such ligands results in two diastereomeric forms for the complex which can be separated by HPLC. We demonstrated that the diastereomer ratio for Ln(III) DTPA derivatives (approximately 60:40) remains constant throughout the lanthanide series, in contrast to Ln(III) EPTPA derivatives, where it varies as a function of the cation size with a maximum for the middle lanthanides (DTPA(5-) = diethylenetriaminepentaacetate; EPTPA(5-) = ethylenepropylenetriaminepentaacetate). The interconversion of the two diastereomers, studied by HPLC, is a proton-catalyzed process (k(obs) = k(1)[H(+)]). It is relatively fast for [Gd(EPTPA-bz-NH(2))(H(2)O)](2-) but slow enough for [Gd(DTPA-bz-NH(2))(H(2)O)](2-) to allow investigation of pure individual isomers (isomerization rate constants are k(1) = (3.03 +/- 0.07) x 10(4) and 11.6 +/- 0.5 s(-1) M(-1) for [Gd(EPTPA-bz-NH(2))(H(2)O)](2)(-) and [Gd(DTPA-bz-NH(2))(H(2)O)](2-), respectively). Individual water exchange rates have been determined for both diastereomers of [Gd(DTPA-bz-NH(2))(H(2)O)](2-) by a variable-temperature (17)O NMR study. Similarly to Ln(III) EPTPA derivatives, k(ex) values differ by a factor of 2 (k(ex)(298) = (5.7 +/- 0.2) x 10(6) and (3.1 +/- 0.1) x 10(6) s(-1)). This variance in the exchange rate has no consequence on the proton relaxivity of the two diastereomers, since it is solely limited by fast rotation. However, such difference in k(ex) will affect proton relaxivity when these diastereomers are linked to a slowly rotating macromolecule. Once the rotation is optimized, slow water exchange will limit relaxivity; thus, a factor of 2 in the exchange rate can lead to a remarkably different relaxivity for the diastereomer complexes. These results have implications for future development of Gd(III)-based, macromolecular MRI contrast agents, since the use of chiral bifunctional ligands in their synthesis inevitably generates diastereomeric complexes.

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Section: Resultsmentioning

confidence: 99%

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

et al. 2005

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“…This is in qualitative agreement with the NMR data of Muller and coworkers. 10 Using the Solomon-Bloembergen-Morgan model modified by Powell et al 27 to analyze 1 H nuclear magnetic relaxation dispersion (NMRD) and 17 O NMR relaxation rates and chemical shifts, they obtained a transient zero-field splitting magnitude parameters D 2 = 1.2 × 10 20 s −2 and correlation time s v = 12.6 ps. With these numbers, one can calculate the transverse electron spin relaxation rates and the peak-to-peak width.…”

Section: Epr Spectroscopymentioning

confidence: 99%

The effect of pyridinecarboxylate chelating groups on the stability and electronic relaxation of gadolinium complexes

et al. 2005

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The ligand N,N -bis [(6-carboxy-2-pyridylmethyl]ethylenediamine-N,N -diacetic acid (H 4 bpeda) was synthesised using an improved procedure which requires a reduced number of steps and leads to a higher yield with respect to the published procedure. It was obtained in three steps from diethylpyridine-2,6-dicarboxylate and commercially available ethylenediamine-N,N -diacetic acid with a total yield of ∼20%. The crystal structure of the hexa-protonated form of the ligand which was determined by X-ray diffraction shows that the four carboxylates and the two amines are protonated. The crystal structure of the polynuclear complex [Gd(bpeda)(H 2 O) 2 ] 3 [Gd(H 2 O) 6 ] 2 Cl 3 (2), isolated by slow evaporation of a 1 : 1 mixture of GdCl 3 and H 4 bpeda at pH ∼ 1, was determined by X-ray diffraction. In complex 2 three [Gd(bpeda)(H 2 O) 2 ] units, containing a Gd(III) ion ten-coordinated by the octadentate bpeda and two water molecules, are connected in a pentametallic structure by two hexa-aquo Gd 3+ cations through four carboxylato bridges. The protonation constants (pK a1 = 2.9(1), pK a2 = 3.5(1), pK a3 = 5.2(2), and pK a4 = 8.5(1)) and the stability constants of the complexes formed between Gd(III) and Ca(II) ions and H 4 bpeda (log b GdL = 15.1(3); log b CaL = 9.4(1)) were determined by potentiometric titration. The unexpected decrease in the stability of the gadolinium complex and of the calcium complex of the octadentate ligand bpeda 4− with respect to the hexadentate ligand edta 4− has been interpreted in terms of an overall lower contribution to stability of the metal-nitrogen interactions. The EPR spectra display very broad lines (apparent DH pp ∼800-1200 G at X-band and 90-110 G at Q-band depending on the temperature), indicating a rapid transverse electron spin relaxation. At X-band, Gd(bpeda) is among the fastest relaxing Gd 3+ complexes to date suggesting that the presence of pyridinecarboxylate chelating groups in itself does not lead to slow electron relaxation.

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“…[9][10][11] Other experimental techniques are oxygen-17 NMR, [7] deuterium NMR, [12] and electron spin resonance spectroscopy. [13] Besides the critical question of the validity of the theoretical model for the description of spin relaxation, [14] a satisfactory analysis of the experimental data is hampered by the large number of parameters entering the models. A more reliable data analysis is obtained by performing a simultaneous fit of all experimental data together; [15] but nevertheless, the correlation between certain parameters remains high in general.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Spin Relaxation Parameters of MRI Contrast Agents – Insight from Quantum Mechanical Calculations

Yazyev

Helm

2007

Eur J Inorg Chem

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Keywords: Relaxivity / Hyperfine interactions / Quantum chemistry / Gadolinium / MRI contrast agent Nuclear magnetic relaxation in the presence of paramagnetic centres has gained increasing interest in recent years partly due to its importance for contrast agents in magnetic resonance imaging. Rational design of new more efficient agents is possible as a result of a better understanding of the underlying relaxation mechanisms. Quantum chemical calculations together with molecular dynamics simulations allow obtaining fundamental parameters such as quadrupole coupling constants and hyperfine interaction tensors directly at a molecular level. Recent results are presented on gadolinium(III) ions in aqueous solution and on [Gd(DOTA)(H 2 O)] -, a commercial MRI contrast agent. Isotropic hyperfine coupling

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Molecular Dynamics of Gd(III) Complexes in Aqueous Solution by HF EPR

Cited by 7 publications

References 52 publications

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

The effect of pyridinecarboxylate chelating groups on the stability and electronic relaxation of gadolinium complexes

Nuclear Spin Relaxation Parameters of MRI Contrast Agents – Insight from Quantum Mechanical Calculations

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Molecular Dynamics of Gd(III) Complexes in Aqueous Solution by HF EPR

Cited by 7 publications

References 52 publications

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

The effect of pyridinecarboxylate chelating groups on the stability and electronic relaxation of gadolinium complexes

Nuclear Spin Relaxation Parameters of MRI Contrast Agents – Insight from Quantum Mechanical Calculations

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Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics

Separation and Characterization of the Two Diastereomers for [Gd(DTPA-bz-NH₂)(H₂O)]^2-, a Common Synthon in Macromolecular MRI Contrast Agents: Their Water Exchange and Isomerization Kinetics