Spectroscopic Characterization of the 3+ and 2+ Oxidation States of Europium in a Macrocyclic Tetraglycinate Complex

Abstract

The +3 and +2 oxidation states of europium have drastically different magnetic and spectroscopic properties. Electrochemical measurements are often used to probe EuIII/II oxidation state changes, but a full suite of spectroscopic characterization is necessary to demonstrate conversion between these two oxidation states in solution. Here, we report the facile conversion of a EuIII tetraglycinate complex into its EuII analogue. We present electrochemical, luminescence, electron paramagnetic resonance, UV–visible, and NMR spectroscopic data demonstrating complete reversibility from the reduction and oxidation of the +3 and +2 oxidation states, respectively. The EuII-containing analogue has kinetic stability within the range of clinically approved GdIII-containing complexes using an acid-catalyzed dissociation experiment. Additionally, we demonstrate that the +3 and +2 oxidation states provide redox-responsive behavior through chemical exchange saturation transfer or proton relaxation, respectively. These results will be applicable to a wide range of redox-responsive contrast agents and Eu-containing complexes.

Responsive, Water‐Soluble Europium(III) Luminescent Probes

“…The reduction potential for Eu 3+ /Eu 2+ is the lowest in the lanthanide series, e.g. --0.35 V for the aqua ion, and about --1.1 V for Eu(III) complexes with many strongly coordinating octadentate ligands that stabilise Eu(III) with respect to Eu(II) [4], [5] . The energy of these broad LMCT bands, with widths in the range 5000--15000 cm --1 , varies considerably depending on the electron--donating ability of the ligand [6] .…”

The Role of Coordination Environment and pH in Tuning the Oxidation Rate of Europium(II)

“…[5,6] Additionally, 1 -Eu II , EuCl 2 (aq), and 2 -Eu II encompass a relatively wide range in reduction potentials (Table 1) with 1 -Eu II being 374 mV more negative than EuCl 2 (aq) [7] and 2 -Eu II being 547 mV more positive than EuCl 2 (aq). [17] Although we have observed rapid oxidation of Eu II by gaseous diatomic molecules, such as O 2 and NO, we elected to study reaction kinetics with non-gaseous oxidants for the ease of quantifying and handling in an inert atmosphere.…”

“…[7] Briefly, 1 -Eu III ·9H 2 O (2.00 mg, 2.12 µmol, Macrocyclics) was reduced with Zn dust (30 mg, 0.46 mmol) in water (1.00 mL) followed by filtration through a 0.2 µm hydrophilic filter. DOWEX cation-exchange resin was used to exchange Zn 2+ with Na + , and resin was removed by filtration through a 0.2 µm hydrophilic filter.…”

“…Inner-sphere water and counterions have been omitted for clarity. Reported E 1/2 values are versus normal hydrogen electrode and are below 1 -Eu II , [7] , EuCl 2 (aq), [17] and 2 -Eu II . [17] …”

“…[4–7] Out of the lanthanide ions, Eu II is uniquely poised for oxidation-responsive MRI because (1) some Eu II -containing complexes are stable in aqueous media, (2) Eu II provides positive (bright or T 1 -shortening) contrast enhancement in MRI, (3) the E 1/2 of Eu II/III can be tuned over a physiologically relevant range, and (4) the +2 and +3 oxidation states of Eu exhibit different magnetic and spectroscopic characteristics making responsive imaging feasible. [7,8] The oxidation-responsive behavior of Eu II -containing complexes has been documented in vivo, [5,6] making the kinetics of oxidation under physiological conditions important to understand for the rational design of new complexes. Accordingly, there is a need for kinetic and thermodynamic analyses to enable a detailed understanding of Eu II -containing complexes for responsive MRI.…”