Prediction of Gd(III) complex thermodynamic stability

Uzal-Varela, Rocío; Rodríguez-Rodríguez, Aurora; Wang, Huan; Esteban‐Gómez, David; Brandariz, Isabel; Gale, Eric M.; Caravan, Peter; Platas‐Iglesias, Carlos

doi:10.1016/j.ccr.2022.214606

Cited by 11 publications

(21 citation statements)

References 150 publications

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“…Figure 4 provides a comparison of the contributions of the different structural descriptors to Mn(II) and Gd(III) 30 complex stabilities. The Δlog K values of most structural descriptors fall close to the line of identity, indicating that they contribute to a similar extent to Gd(III) and Mn(II) complex stability.…”

Section: Resultsmentioning

confidence: 99%

“…Structural Descriptors. The descriptors used to predict the thermodynamic stability of Mn(II) complexes are essentially those used previously for Gd(III) 30 and are listed in Table 3. Linear polyaminopolycarboxylate ligands are described by the corresponding number of amine N atoms, denoted as N, and the number of acetic acid groups C. For instance, H 4 EDTA is described as nN = 2 + nC = 4, where n indicates the number of groups of a given class.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…In a recent paper, we proposed an empirical correlation to predict and rationalize the thermodynamic stabilities of Gd(III) complexes with polyaminopolycarboxylate ligands . We showed that the thermodynamic stability constants and pGd values can be approximated to a good accuracy using structural descriptors.…”

Section: Introductionmentioning

confidence: 99%

“…20−29 In a recent paper, we proposed an empirical correlation to predict and rationalize the thermodynamic stabilities of Gd(III) complexes with polyaminopolycarboxylate ligands. 30 We showed that the thermodynamic stability constants and pGd values can be approximated to a good accuracy using structural descriptors. The contribution of each structural descriptor (ligand motif) to complex stability was obtained by a least-squares fitting procedure to stability data reported in the literature.…”

Section: ■ Introductionmentioning

confidence: 99%

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Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors

et al. 2022

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We present a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes, defined by the equilibrium constants (log K MnL values) and the values of pMn obtained as −log[Mn] free for total metal and ligand concentrations of 1 and 10 μM, respectively. We used structural descriptors to analyze the contributions to complex stability of different structural motifs in a quantitative way. The experimental log K MnL and pMn values can be predicted to a good accuracy by adding the contributions of the different motifs present in the ligand structure. This allowed for the identification of features that provide larger contributions to complex stability, which will be very helpful for the design of efficient chelators for Mn(II) complexation. This issue is particularly important to develop Mn(II) complexes for medical applications, for instance, as magnetic resonance imaging (MRI) contrast agents. The analysis performed here also indicates that coordination number eight is more common for Mn(II) than is generally assumed, with the highest log K MnL values generally observed for hepta- and octadentate ligands. The X-ray crystal structure of [Mn 2 (DOTA)(H 2 O) 2 ], in which eight-coordinate [Mn(DOTA)] 2– units are bridged by six-coordinate exocyclic Mn(II) ions, is also reported.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors

et al. 2022

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“…Thus, the combined effects of the replacement of ether oxygen atoms in H 4 EGTA with the (stronger) N donor atoms of phenanthroline and of the rigidity of the tricyclic aromatic system appear to have a beneficial effect on the thermodynamic stability of the corresponding Gd(III) complex. An empirical correlation developed recently to predict the stability of Gd(III) complexes (using structural descriptors) 46 determined experimentally, while the experimental stability constant obtained for the complex with [Gd(FENTA)] − is 1.6 log K units higher than that predicted by the empirical correlation. This likely reflects a certain ligand pre-organization associated with the presence of a rigid phenantroline unit, which contributes to an increased complex stability.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Physico-Chemical Characterization of a Highly Rigid Gd(III) Complex Formed with a Phenanthroline Derivative Ligand

et al. 2022

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The discovery of the nephrogenic systemic fibrosis (NSF) and its link with the in vivo dissociation of certain Gd(III)-based contrast agents (CAs) applied in the magnetic resonance imaging (MRI) induced a still growing research to replace the compromised agents with safer alternatives. In recent years, several ligands were designed to exploit the luminescence properties of the lanthanides, containing structurally constrained aromatic moieties, which may form rigid Gd(III) complexes. One of these ligands is (1,10-phenanthroline-2,9-diyl)bis(methyliminodiacetic acid) (H 4 FENTA) designed and synthesized to sensitize Eu(III) and Tb(III) luminescence. Our results show that the conditional stability of the [Gd(FENTA)] − chelate calculated for physiological pH (pGd = 19.7) is similar to those determined for [Gd(DTPA)] 2− (pGd = 19.4) and [Gd(DOTA)] − (pGd = 20.1), routinely used in the clinical practice. The [Gd(FENTA)] − complex is remarkably inert with respect to its dissociation (t 1/2 = 872 days at pH = 7 and 25 °C); furthermore, its relaxivity values determined at different field strengths and temperatures (e.g., r 1p = 4.3 mM −1 s −1 at 60 MHz and 37 °C) are ca. one unit higher than those of [Gd(DTPA)] 2− (r 1p = 3.4 mM −1 s −1 ) and [Gd(DOTA)] − (r 1p = 3.1 mM −1 s −1 ) under the same conditions. Moreover, significant improvement on the relaxivity was observed in the presence of serum proteins (r 1p = 6.9 mM −1 s −1 at 60 MHz and 37 °C). The luminescence lifetimes recorded in H 2 O and D 2 O solutions indicate the presence of a water molecule (q = 1) in the inner sphere of the complex directly coordinated to the metal ion, possessing a relatively high water exchange rate (k ex 298 = 29(2) × 10 6 s −1 ). The acceleration of the water exchange can be explained by the steric compression around the water binding site due to the rigid structure of the complex, which was supported by DFT calculations. On the basis of these results, ligands containing a phenanthroline platform have great potential in the design of safer Gd(III) agents for MRI.

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Structural Changes to the Gd‐DTPA Complex at Varying Ligand Protonation State

Summers,

O'Brien,

Sobrinho

et al. 2023

Eur J Inorg Chem

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Diethylenetriaminepentaacetic acid (DTPA) is a chelating agent whose complex with the Gd3+ ion is used in medical imaging. DTPA is also used in lanthanide‐actinide separation processes. As protonation of the DTPA ligand can facilitate dissociation of the Gd3+ ion from the Gd‐DTPA complex, this work investigates the coordination structures of the aqueous Gd3+ ion and its environment when chelated by DTPA in eight different DTPA protonation states. Both classical and ab initio molecular dynamics (MD) simulations are conducted to model the solvated complexes. Extended X‐ray absorption fine structure (EXAFS) measurements of the Gd3+aqua ion, and the Gd‐DTPA complex at pH 1 and 11, are compared to EXAFS spectra predicted from the MD simulations to verify the accuracy of the MD structures. The findings of this work provide atomic‐level details into the fluctuating Gd‐DTPA complex environment as the DTPA ligand gradually detaches from the Gd3+ ion with increased protonation.

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Prediction of Gd(III) complex thermodynamic stability

Cited by 11 publications

References 150 publications

Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors

Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors

Physico-Chemical Characterization of a Highly Rigid Gd(III) Complex Formed with a Phenanthroline Derivative Ligand

Structural Changes to the Gd‐DTPA Complex at Varying Ligand Protonation State

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