Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

Porcar-Tost, Oriol; Olivares, José A.; Pallier, Agnès; Esteban‐Gómez, David; Illa, Ona; Platas‐Iglesias, Carlos; Tóth, Éva; Ortuño, Rosa M.

doi:10.1021/acs.inorgchem.9b02044

Cited by 11 publications

(5 citation statements)

References 69 publications

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“…However, they agree well with the relaxivity of the rigid, monohydrated [Gd(CBDDADPA)(H 2 O)] − complex, r 1p = 5.6 mM –1 s –1 (Scheme S1). The r 1p values of [Gd(FENTA)] − decrease by increasing the temperature from 25 to 37 °C at both magnetic fields, indicating that the relaxivity is controlled by fast rotation, as it has earlier been reported for several low molecular weight Gd(III) complexes . To get information on the relaxivity of the [Gd(FENTA)] − complex in human serum, we performed measurements for both field strengths at 25 and 37 °C.…”

Section: Resultssupporting

confidence: 73%

“…DFT predicted similar Gd-N phenanthroline distances (2.64 and 2.67 Å) and bite-angle of the phenanthroline moiety (61.2°) compared to those reported for a bis(phenanthroline)-gadolinium(III) complex (2.60 and 2.57 Å and 63.5°) . The Gd-N amine distances are calculated to be 2.67 and 2.73 Å, which are shorter than those of highly rigid open-chain gadolinium(III) complexes possessing a cyclobutene ring in the ligand backbone . Thus, it is reasonable to assume that the rigid phenanthroline backbone pre-organizes the coordination cavity and, as a result, enhances the inertness of the complex.…”

Section: Resultssupporting

confidence: 60%

“…61 The Gd-N amine distances are calculated to be 2.67 and 2.73 Å, which are shorter than those of highly rigid open-chain gadolinium-(III) complexes possessing a cyclobutene ring in the ligand backbone. 62 Thus, it is reasonable to assume that the rigid phenanthroline backbone pre-organizes the coordination cavity and, as a result, enhances the inertness of the complex. The distance between the Gd 3+ and coordinated water molecule is 2.45 Å, which falls into the range of the first coordination shell of water.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 73%

Section: Resultssupporting

confidence: 60%

Section: ■ Results and Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Encouraged by the results, the Cu 2+ transmetallation was also evaluated as the Cu 2+ was involved in many physiological processes and empirically displayed strong coordinating capability. [ 27 ] As implied in Figure 3g, the T 1 of fe Gd‐N x C maintained well for two months, on the contrary, Gd‐DTPA displayed an obvious Gd 3+ leakage, namely, the initial T 1 value of Gd‐DTPA (0.95 s) quickly reduced to 0.36 s in the following days. These results suggested that the Gd 3+ in fe Gd‐N x C was more resistant to dissociation under physiological conditions than that of Gd‐DTPA.…”

Section: Resultsmentioning

confidence: 91%

Single‐Atom Gd Nanoprobes for Self‐Confirmative MRI with Robust Stability

Luo

Liu

et al. 2023

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which could exacerbate nephrogenic systemic fibrosis, and deposit in the heart, kidney, skin and even in the brain, threatening the patient's health. [5] To overcome these shortcomings, Gdbased inorganic nanoparticles (NPs), such as Gd 2 O 3 , [6] NaGdF 4 , [7] Gd-doped oxide, [8] were reported on account of the higher stability of Gd 3+ ions in Gd NPs-based CAs. The unsaturated coordination properties of Gd 3+ exposed at the NPs surface can be used to increase the hydration sites, which contribute to the high T 1 relaxivity for MRI. [9] While metal ions inside NPs were not available for direct chemical exchange with protons and thus attenuated the MRI signal. Therefore, increasing the number of accessible paramagnetic metal centers would directly increase the relaxivity. Recently, single-atom materials (SAMs) have been reported and extensively utilized in catalysis, pollution treatment, biosensing, and tumor therapy. [10] However, few studies have focused on the construction of SAMs as MRI contrast agents. [11] We anticipated that SAMs such as single-atom Gd nanomaterial could provide as a good substitute for traditional Gd complex by simulating the coordination environment of paramagnetic metal with ligands at the atomic level, maximizing the exposure of Gd atom as well as possessing better structural stability, which was conducive to enhance imaging contrast. In addition, according to Solomon-Bloembergen-Morgan theory, [12] the enhanced relaxivity was mainly related to increasing the number of coordination water in the inner layer (q), shortening water exchange lifetime (τ M ), prolonging molecular rotation time (τ R ) and facilitating diffusion related time of water molecules (τ D ). [13] Therefore, the fabrication of Gd SAMs with open coordination sites, large surface area, and hydrophilic properties are highly desirable. In another aspect, due to the fluctuation of endogenous paramagnetic species as well as the concentration gradient of CAs, false-positive signals were frequently encountered. [14] As we know, T 1 /T 2 dual-mode MRI CAs have attracted great research interest, with T 1 -weighted MRI being used to assess adipose tissues or anatomical structures, while T 2 -weighted MRI for assessing waterrich structures or local inflammation. [15] Thus, self-confirmative CAs especially with T 1 /T 2 dual-modal MRI were able to provide an accurate diagnosis. [16] Herein, we constructed a highly stable single atom Gd-based MRI CA through spatial confinement and controllable etching strategy for effective T 1 /T 2 dual-mode MRI with excellent Gadolinium (Gd)-based complexes are extensively utilized as contrast agents (CAs) in magnetic resonance imaging (MRI), yet, suffer from potential safety concerns and poor tumor targeting. Herein, as a mimic of Gd complex, single-atom Gd nanoprobes with r 1 and r 2 values of 34.2 and 80.1 mM −1 s −1 (far higher than that of commercial Gd CAs) at 3 T are constructed, which possessed T 1 /T 2 dual-mode MRI with excellent stability and good tumor targeting ability. Specificall...

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“…This approach provided a high degree of accuracy in the prediction of Gd-O water distances and the localization of spin density at the O nuclei of the water molecule. 18,42,43 Moreover, dispersion corrections were incorporated into our DFT calculations for a more accurate prediction of inter-and intramolecular interactions. Details are provided in the Experimental section.…”

Section: Dft Calculationsmentioning

confidence: 99%

Bipyridil-based chelators for Gd(iii) complexation: kinetic, structural and relaxation properties

Bunda,

Lihi,

Szaniszló

et al. 2023

Dalton Trans.

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Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness

Cited by 11 publications

References 69 publications

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

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

Single‐Atom Gd Nanoprobes for Self‐Confirmative MRI with Robust Stability

Bipyridil-based chelators for Gd(iii) complexation: kinetic, structural and relaxation properties

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