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

Abstract

Metal‐based contrast agents for magnetic resonance imaging present a promising avenue to image hypoxia. EuII‐based contrast agents have a unique biologically relevant redox couple, EuII/III, that distinguishes this metal for use in hypoxia imaging. To that end, we investigated a strategy to enhance the contrast‐enhancing capabilities of EuII‐based cryptates in magnetic resonance imaging by controlling the rotational dynamics. Two dimetallic, EuII‐containing cryptates were synthesized to test the efficacy of rigid versus flexible coupling strategies. A flexible strategy to dimerization led to a modest (114 %) increase in contrast enhancement per Eu ion (60 MHz, 298 K), but a rigid linking strategy led to an excellent (186 %) increase in contrast enhancement despite this compound′s having the smaller molecular mass of the two dimetallic complexes. We envision the rigid linking strategy to be useful in the future design of potent EuII‐based contrast agents for magnetic resonance imaging.

Versatile Para‐Substituted Pyridine Lanthanide Coordination Complexes Allow Late Stage Tailoring of Complex Function

“…With Eu(III) complexes, we show here how this approach opens up various possibilities: it enables the tailoring of excited state energies involving the chromophore and modifies the metal ion excited state lifetime for luminescent probe development; [12–14] it permits the introduction of functionality that allows subsequent one‐step conjugation processes; [15–18] it allows access to simple derivatives that may serve as activity based probes, [19–21] for example for H 2 S detection; [22–24] it provides precursors that are one reduction step away from the corresponding Eu(II) complexes that might function as magnetic or luminescent probes or photocatalysts [25–27] . For each of these aspects, the p −NO 2 pyridyl complexes are particularly attractive, and their potential has been highlighted earlier, notably in their reactivity towards Cys‐thiol residues for selective peptide or protein conjugation [15–17,28–29] .…”

To Chelate Thallium(I) - Synthesis and Evaluation of Kryptofix-based Chelators for 201Tl

“…The reaction was complete after 1 h at room temperature and did not require overnight stirring as described in some literature reports. [19] Compound 5 was obtained by refluxing 4 in BH3 . THF overnight and was used without further purification.…”

“…The NMR data matched that reported previously. [19] 1 H NMR (400 MHz, CDCl3) δ 7.82 (dd, 3 JH-H = 2.6, 8.9 Hz, 1H), 7.77 (d, 3 JH-H = 2.6 Hz, 1H), 7.00 (d, 3 JH-H = 8.9 Hz, 1H), 5.63 (d, 3 JH-H = 15.0 Hz, 1H), 5.47 (d, 3 JH-H = 15.1 Hz, 1H), 4.83-4.75 (m, 2H), 4.38-4.26 (m, 2H), 3.92-3.47 (m, 20H), 3.28-3.17 (m, 2H), 2.84-2.75 (m, 2H).…”

“…The NMR data matched that reported previously. [19] 1 H NMR (400 MHz, CDCl3) δ 7.98 (dd, 3 JH-H = 2.6, 9.0 Hz, 1H), 7.92 (d, 3 JH-H = 2.6 Hz, 1H), 7.27 (d, 3 JH-H = 9.0 Hz, 1H). 4.39 (t, 3 JH-H = 4.8 Hz, 2H), 4.34 (t, 3…”

“…K222-N3 and K222-DBCO (Figure 2). The synthetic strategy towards K222-NH2 was based on works by Gansow [17] , Pettit [18] , and Allen [19] adjusted with our own optimisations (Scheme 1). Compound 1 was obtained by reacting 4-nitrocatechol with ethyl bromoacetate in acetone in the presence of sodium carbonate.…”