Dinuclear Fe(III) Hydroxypropyl-Appended Macrocyclic Complexes as MRI Probes

Abstract

Four high-spin Fe­(III) macrocyclic complexes, including three dinuclear and one mononuclear complex, were prepared toward the development of more effective iron-based magnetic resonance imaging (MRI) contrast agents. All four complexes contain a 1,4,7-triazacyclononane macrocyclic backbone with two hydroxypropyl pendant groups, an ancillary aryl or biphenyl group, and a coordination site for a water ligand. The pH potentiometric titrations support one or two deprotonations of the complexes, most likely deprotonation of hydroxypropyl groups at near-neutral pH. Variable-temperature 17O NMR studies suggest that the inner-sphere water ligand is slow to exchange with bulk water on the NMR time scale. Water proton T 1 relaxation times measured for solutions of the Fe­(III) complexes at pH 7.2 showed that the dinuclear complexes have a 2- to 3-fold increase in r 1 relaxivity in comparison to the mononuclear complex per molecule at field strengths ranging from 1.4 T to 9.4 T. The most effective agent, a dinuclear complex with macrocycles linked through para-substitution of an aryl group (Fe2(PARA)), has an r 1 of 6.7 mM–1 s–1 at 37 °C and 4.7 T or 3.3 mM–1 s–1 per iron center in the presence of serum albumin and shows enhanced blood pool and kidney contrast in mice MRI studies.

Porous Silica Nanospheres with a Confined Mono(aquated) Mn(II)-Complex: A Potential T1–T2 Dual Contrast Agent for Magnetic Resonance Imaging

“…Contrast agents are classified into two groups depending on the overall signal enhancement property in the region of interest. 1–2 The positive contrast agents ( T 1 -contrast agents), which are mainly low-molecular-weight Gd­(III), − Mn­(II), − , and Fe­(III) , complexes, render brighter images by enhancing the signal intensity, while a loss in the signal intensity results in darker images in the presence of negative contrast agents ( T 2 -contrast agents), which are usually superparamagnetic nanoparticles. − The clinical applications of T 2 -contrast agents have some drawbacks. Because of the image darkening property, the use of T 2 -contrast agents misleads with the signals that appeared due to endogenous conditions, , such as metal ion depositions, calcification, blood clots, hemorrhage, and magnetic susceptibility artifacts.…”

“…8 Contrast agents are classified into two groups depending on the overall signal enhancement property in the region of interest. 1−2 The positive contrast agents (T 1 -contrast agents), which are mainly low-molecular-weight Gd(III), 9−18 Mn-(II), [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]69 and Fe(III) 36,37 complexes, render brighter images by enhancing the signal intensity, while a loss in the signal intensity results in darker images in the presence of negative contrast agents (T 2 -contrast agents), which are usually superparamagnetic nanoparticles. 38−41 The clinical applications of T 2 -contrast agents have some drawbacks.…”

Inner-sphere electron transfer at the ruthenium-azo interface

“…On the other hand, oxidised paramagnetic [ 2 ]ClO 4 showed broad 1 H-NMR resonances over a wide chemical shift range of δ = ±40 ppm due to contact and pseudo-contact shift effects. 15 The one-electron paramagnetic features of oxidised [ 2 ]ClO 4 (Ru III -abim˙ − -Ru III , S = 1/2) due to the antiferromagnetic coupling of one of the Ru( iii ) ions and the abim radical were corroborated based on the Evans method 16 ( μ eff = 1.78 BM in CDCl 3 at 298 K, see ESI†) and on its metal-based anisotropic EPR spectrum, with 〈 g 〉/Δ g = 2.141/0.541 (Fig. 4 and Table 2).…”

Enzyme Control Over Ferric Iron Magnetostructural Properties

“…[12a, 18] Alternately, incorporating metal complexes into higher molecular weight multimeric structures or ligand modifications to promote plasma protein binding represent established strategies by which to increase rotational correlation time and thus r 1 . [15,16,19] We also note that our ligand design approach is broadly applicable to hydrolytic enzymes. Future work building upon our proof concept data will focus on further optimizing the r 1 increase upon switching from antiferromagnetically coupled to paramagnetic Fe 3 + , on developing sensors for enzyme markers of human disease, and on evaluating and optimizing enzyme "turn-on" kinetics, in vivo stability, and pharmacokinetics.…”