Intramolecular Hydrogen Bonding Restricts Gd–Aqua‐Ligand Dynamics

Boros, Eszter; Srinivas, Raja; Kim, Hee‐Kyung; Raitsimring, Arnold M.; Astashkin, Andrei V.; Poluektov, Oleg G.; Niklas, Jens; Horning, Andrew D.; Tidor, Bruce; Caravan, Peter

doi:10.1002/anie.201702274

Cited by 19 publications

(14 citation statements)

References 28 publications

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“…This effect has been observed in similar Gd complexes and has led to an increase in relaxivity of a similar order of magnitude as it was observed for gadobutrol, when compared with gadoterate and gadoteridol in this study. 38…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T

et al. 2019

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The relaxivities of 3 macrocyclic gadolinium-based contrast agents (GBCAs) were determined in human plasma and blood under standardized and clinically relevant laboratory conditions. Methods: The T1 relaxivity, r1, was determined in human plasma at 1.5, 3, and 7 T, and in human blood at 3 T at 37°C in phantoms containing 4 different concentrations of the macrocyclic GBCAs gadobutrol, gadoteridol, and gadoterate. An inversion recovery turbo spin echo sequence was used to generate images with several inversion times. The T1-times were obtained by fitting the signal intensities to the signal equation. r1 was obtained by a 1/y-weighted regression of the T1-rates over the concentration of the GBCAs.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T

et al. 2019

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“…66,69,82 At a higher level of detail, not only is the form of the complex important, but the orientation and interactions between the ligand scaffold and capping ligand have to be included to adequately describe the magnetic properties of some complexes. 83 Note that water exchange does not change the structure of the lanthanide(III) complex, and k ex here is used to illustrate a property that differs between two lanthanide(III) species in solution.…”

Section: ■ Introductionmentioning

confidence: 99%

Including and Declaring Structural Fluctuations in the Study of Lanthanide(III) Coordination Chemistry in Solution

2019

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The physicochemical properties of lanthanide-(III) ions are directly linked to the structure of the surrounding ligands. Rapid ligand exchange prohibits direct structure−property relationships from being formed for simple complexes in solution because the property measured will be an average over several structures. For kinetically inert lanthanide(III) complexes, the simpler speciation may alleviate the problem, yet the archetypical complexes formed by ligands derived from cyclen are known to have at least four different forms in solutioneach with a variation in the crystal field that gives rise to significantly different properties. Slow interchange between forms has been engineered, so that a single complex geometry can be studied, but fast or intermediate interchange between forms is much more commonly observed. The rapid structural fluctuation can report on the changing chemical environment and can be disregarded if a specific property of a lanthanide(III) complex is exploited in an application. However, if we are to understand the chemistry of the lanthanide(III) ions in solution, we must include the structural fluctuation that takes place even in kinetically inert lanthanide(III) complexes in our studies. Here, we have scrutinized the processes that determine the speciation of lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA)-like ligands, in particular the processes that enable exchange between forms that have different physicochemical properties, exemplified by the exchange between the diastereomeric capped square-antiprismatic (cSAP) and capped twisted-square-antiprismatic (cTSAP) forms of DOTA-like lanthanide(III) complexes. In the characterization of a kinetically inert f-element complex, understanding the structural fluctuation in the system is critical because a single observed property can arise from a weighted average, from all forms present, or from a single form with a dominating contribution. Further, the experimental condition will influence both the distribution of lanthanide(III) species in solution and the rates of the processes that change the coordination sphere of the lanthanide(III) ions. This is highlighted using data from a series of cyclen-derived ligands with different pendant arms and different denticity. The data were obtained in experiments that take place on different time scales to show that the rate of the process that results in a structural change must be considered against the time of the experiment. We conclude that the structural fluctuations must be taken into account and that they cannot be predicted from the ligand structure. Thus, an estimate of the exchange rates between forms, the relative concentrations of the specific forms, and the effect of the specific structure of each form of the complex must be included in the description of the solution properties of f-element chelates.

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“…As Gd′ is soluble in water, the longitudinal r1 relaxivity of a water solution of Gd′ was measured at 22 °C and 9.4 T, yielding a value of 0.71 mM −1 s −1 (Figure 5). This value demonstrates that, in spite of the nonacoordination displayed by the Gd 3+ ion in this complex, and the presence of a water molecule in its inner sphere, even fixed by classic hydrogen bonds [55] Gd′ shows a low r1 relaxation and, accordingly, it is not appropriate as contrast agent. The frontal part of the L 3− ligands with the N and O donor atoms shows not only a coordinating character that encloses metal ions, but also a more hydrophilic character than its rear side [54].…”

Section: Mri Studiesmentioning

confidence: 93%

Filling Tricompartmental Ligands with GdIII and ZnII Ions: Some Structural and MRI Studies

et al. 2018

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Here we report the synthesis and characterization of a mononuclear gadolinium complex (Gd) and two heteronuclear Zn-Gd complexes (ZnGd and Zn2Gd), which contain two similar three-armed ligands that display an external compartment suitable for lanthanoid ions, and two internal compartments adequate for zinc (II) ions [H3L′ = (2-(3-formyl-2-hydroxy-5-methyl phenyl)-1,3-bis[4 -(3-formyl-2-hydroxy-5-methylphenyl)-3-azabut-3-enyl]-1,3-imidazolidine; H3L = 2-(5-bromo-2-hydroxy-3-methoxyphenyl)-1,3-bis[4-(5-bromo-2-hydroxy-3-methoxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine]. The synthetic methods used were varied, but the use of a metalloligand, [Zn2(L)AcO], as starting material was the key factor to obtain the heterotrinuclear complex Zn2Gd. The structure of the precursor dinuclear zinc complex is mostly preserved in this complex, since it is based on a compact [Zn2Ln(L)(OH)(H2O)]3+ residue, with a µ3-OH bridge between the three metal centers, which are almost forming an isosceles triangle. The asymmetric spatial arrangement of other ancillary ligands leads to chirality, what contrasts with the totally symmetric mononuclear gadolinium complex Gd. These features were confirmed by the crystal structures of both complexes. Despite the presence of the bulky compartmental Schiff base ligand, the chiral heterotrinuclear complex forms an intricate network which is predominately expanded in two dimensions, through varied H-bonds that connect not only the ancillary ligands, but also the nitrate counterions and some solvated molecules. In addition, some preliminary magnetic resonance imaging (MRI) studies have been made to determine the relaxivities of the three gadolinium complexes, with apparently improved T1 and T2 relaxivities with increasing zinc nuclearity, since both transversal and longitudinal relaxivities appear to enhance in the sequence Gd < ZnGd < Zn2Gd.

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Intramolecular Hydrogen Bonding Restricts Gd–Aqua‐Ligand Dynamics

Cited by 19 publications

References 28 publications

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T

Including and Declaring Structural Fluctuations in the Study of Lanthanide(III) Coordination Chemistry in Solution

Filling Tricompartmental Ligands with GdIII and ZnII Ions: Some Structural and MRI Studies

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