Carbazole as Linker for Dinuclear Gadolinium‐Based MRI Contrast Agents

Abstract

Ligands able to complex two gadolinium ions have been synthesized and characterized in view of the ability of the complexes to increase the spin relaxation of water protons. All ligands are based on the heptadentate diethylenetriaminetetraacetic acid (DTTA) chelator and carbazole as a rigid linker. Depending on the derivatization on the nitrogen atom of the five‐membered ring, the compounds form small aggregates in aqueous solution, self‐assemble to form micelles or bind to human serum albumin. In all cases, this leads to a marked increase in 1H relaxivity at nuclear Larmor frequencies between 20 and 60 MHz. Water exchange on the gadolinium ions as measured by 17O NMR relaxation is fast enough not to limit relaxivity. 1H nuclear magnetic relaxation dispersion profiles were also measured and analyzed using Solomon–Bloembergen–Morgan theory including Lipari–Szabo treatment to include internal motion or anisotropic rotation.

A Gadolinium(III) Complex Based on the Thymine Nucleobase With Properties Suitable for Magnetic Resonance Imaging Applications

“…7 and 8). These results show relaxivity values for 1 that are much higher than those of commercial MR imaging contrast agents currently employed on 3 T equipments [32], which make 1 potentially useful.…”

“…The relaxometric properties of compound 1 as a potential high-field MR imaging contrast agent were evaluated [32]. 13 samples of 1 were prepared in physiological serum with concentrations covering the range of 0.0-3.2 mM and were measured on a clinical MR scanner (Philips Achieva 3T) by using the volumetric head 8 channels SENSE coil (Fig.…”

Rational Design of High‐Relaxivity EuII‐Based Contrast Agents for Magnetic Resonance Imaging of Low‐Oxygen Environments

“…Our system for Eu II drew inspiration from linking strategies used with isoelectronic Gd III , in which rigidity of linkages greatly enhances relaxivity [21a,c,e‐k] . With Gd III ‐containing agents, slowing the rotational rates of complexes ( τ R −1 ) by adding molecular mass leads to increases in relaxivity [21a,c,e‐k] .…”

“…Our system for Eu II drew inspiration from linking strategies used with isoelectronic Gd III , in which rigidity of linkages greatly enhances relaxivity [21a,c,e‐k] . With Gd III ‐containing agents, slowing the rotational rates of complexes ( τ R −1 ) by adding molecular mass leads to increases in relaxivity [21a,c,e‐k] . Moreover, the local rotation of paramagnetic Gd III ‐containing moieties ( τ RL −1 ) has a larger correlation with enhancement of relaxivity than the global rotational rate of entire agents ( τ RG −1 ) [21a,c,f‐l] .…”

“…With Gd III ‐containing agents, slowing the rotational rates of complexes ( τ R −1 ) by adding molecular mass leads to increases in relaxivity [21a,c,e‐k] . Moreover, the local rotation of paramagnetic Gd III ‐containing moieties ( τ RL −1 ) has a larger correlation with enhancement of relaxivity than the global rotational rate of entire agents ( τ RG −1 ) [21a,c,f‐l] . With the idea of internal rotations that disconnect parts of molecules in mind, two dimetallic cryptates, 1 and 2 , were devised to compare the influence of two different coupling strategies on the relaxivity of Eu II ‐containing cryptates (Figure 1).…”