Structural Features of Europium(II)‐Containing Cryptates That Influence Relaxivity

Abstract

EuII-containing complexes were studied with respect to properties relevant to their use as contrast agents for magnetic resonance imaging. The influences of molecular parameters and field strength on relaxivity were studied for a series of EuII-containing cryptates and their adducts with β-cyclodextrins, poly-β-cyclodextrins, and human serum albumin. Solid- and solution-phase characterization of EuII-containing complexes is presented that demonstrates the presence of inner-sphere molecules of water. Additionally, relaxivity, water-exchange rate, rotational correlation time, and electronic relaxation time were determined using variable-temperature 17O-NMR, nuclear magnetic relaxation dispersion, and electron paramagnetic resonance spectroscopic techniques. We expect that our results will be instrumental in the design of future EuII-based contrast agents.

Reactions in Anhydrous Liquid Ammonia: Syntheses and Crystal Structures of [M(NH3)8]I2 (M = Eu, Yb) with Bicapped Trigonal‐Prismatic Octaammine Lanthanoid(II) Cations

“…[25] coordinated by additional solvent molecules leading to higher coordination numbers. [26][27][28] Only in the aza-cryptate in reference [29] coordination number eight is unambiguous. However, this multidentate aza-cryptand complex is quite unsuitable for comparison to our system as a bicapped trigonal antiprism with much larger Eu-N distances has been reported.…”

Synthesis, Characterization, and Handling of EuII-Containing Complexes for Molecular Imaging Applications

“…Complexes tend to be easier to purify from an excess of Eu II relative to an excess of ligand: the addition of phosphate buffer precipitates excess Eu II from solution as phosphate salts that can be removed with a small (0.2 micrometer) hydrophilic filter to yield a buffered solution of Eu II -containing complex (Garcia and Allen, 2012b ). This technique was used to synthesize Eu II -containing complexes of 8 – 11 and 17 – 19 (Zucchi et al, 2010 ; Garcia and Allen, 2012b ; Garcia et al, 2012 ; Ekanger et al, 2014 , 2015 , 2016b , 2017 ; Lenora et al, 2017 ).…”

“…For an example of purification by precipitation, Eu II 16 was synthesized in tetrahydrofuran: EuI 2 and 16 are soluble in tetrahydrofuran, but Eu II 16 is not, enabling isolation of Eu II 16 by precipitation (Kuda-Wedagedara et al, 2015 ). For an example of purification by crystallization, crystals were grown of cryptates Eu II 4 , Eu II 8 , Eu II 10 , Eu II 11 , Eu II 12 , and Eu II 16 from slow evaporation of a mixture of ligand and Eu II halide in acetone, methanol, or methanol/tetrahydrofuran (Burai et al, 2000 ; Ekanger et al, 2015 ; Kuda-Wedagedara et al, 2015 ; Jin et al, 2016 ; Lenora et al, 2017 ).…”

“…In the case where the formation of a complex was achieved by mixing EuCl 2 with ligands, evidence of 1:1 complex formation in solution was determined by measuring the change in relaxivity as a function of Eu II -to-ligand ratio, a technique known as proton relaxation enhancement (Lauffer, 1987 ; Lenora et al, 2017 ). Another solution-phase technique to monitor complex formation is a Job plot where both ligand and metal ratios are varied, and a unique property of the complex, such as a complex-specific emission, is monitored (Renny et al, 2013 ; Kuda-Wedagedara et al, 2015 ).…”

“…However, because of the crucial differences in preparation and handling between Eu II and Gd III , this review focuses on the synthesis, handling, and characterization of identity and purity of Eu II -containing complexes relevant to molecular imaging (Figure 1 ). For measurements of molecular-imaging-relevant properties for MRI, readers are referred elsewhere (Caravan et al, 1999 ; Burai et al, 2000 , 2002 ; Tóth et al, 2001 ; Botta et al, 2003 ; Garcia et al, 2011 , 2012 ; Garcia and Allen, 2012b ; Ekanger et al, 2014 , 2015 , 2016a , b ; Basal et al, 2017a , b ; Lenora et al, 2017 ; Pierre et al, 2018 ). Because this review is focused on techniques for handling and characterizing discrete, air-sensitive Eu II -containing complexes for molecular imaging, we do not describe other divalent lanthanide complexes, nanoparticles, imaging probes, or nonaqueous Eu II -containing complexes.…”