Systematic Tuning of the Optical Properties of Discrete Complexes of EuII in Solution Using Counterions and Solvents.

We describe a systematic study of the influence of halides and solvents on the optical properties of EuII-containing complexes in solution starting from well-defined crystalline precursors. Anionic halides, chloride and bromide, blue-shift the spectroscopic properties of EuII, whereas neutral ligands, methanol and acetonitrile, cause a red shift. This system provides evidence that EuII has a stronger affinity for chloride, and to some extent bromide, relative to acetonitrile but not methanol. We also describe a simple procedure using an ion-exchange resin for the exchange of iodide counterions to hexafluorophosphate. These findings are a step toward designing ligands that can tune the optical properties of EuII-containing complexes for solution-based applications.

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

Considerable research effort has focused on the in vivo use of responsive imaging probes that change imaging properties upon reacting with oxygen because hypoxia is relevant to diagnosing, treating, and monitoring diseases. One promising class of compounds for oxygen-responsive imaging is EuII-containing complexes because the EuII/III redox couple enables imaging with multiple modalities including magnetic resonance and photoacoustic imaging. The use of EuII requires care in handling to avoid unintended oxidation during synthesis and characterization. This review describes recent advances in the field of imaging agents based on discrete EuII-containing complexes with specific focus on the synthesis, characterization, and handling of aqueous EuII-containing complexes.

Screening of ligands for redox-active europium using magnetic resonance imaging.

We report a screening procedure to predict ligand coordination to EuII and EuIII using magnetic resonance imaging in which bright images indicate complexation and dark images indicate no complexation. Here, paramagnetic GdIII is used as a surrogate for EuIII in the screening procedure to enable detection with magnetic resonance imaging. The screening procedure was tested using a set of eight ligands with known coordination to EuII and EuIII, and results were found to be consistent with expected binding. Validation of the screening procedure with known coordination chemistry enables use with new ligands in the future.

Oxidation-Responsive, EuII/III-Based, Multimodal Contrast Agent for Magnetic Resonance and Photoacoustic Imaging.

We report, for the first time, a multimodal, oxidation-responsive contrast agent for magnetic resonance imaging and photoacoustic imaging that uses the differences in the properties between Eu in the +2 and +3 oxidation states. The enhancement of contrast in T1-weighted magnetic resonance and photoacoustic imaging was observed in the +2 but not in the +3 oxidation state, and the complex is a known chemical exchange saturation transfer agent for magnetic resonance imaging in the +3 oxidation state.

Fluorinated EuII-based multimodal contrast agent for temperature- and redox-responsive magnetic resonance imaging.

Magnetic resonance imaging (MRI) using redox-active, EuII-containing complexes is one of the most promising techniques for noninvasively imaging hypoxia in vivo. In this technique, positive (T1-weighted) contrast enhancement persists in areas of relatively low oxidizing ability, such as hypoxic tissue. Herein, we describe a fluorinated, EuII-containing complex in which the redox-active metal is caged by intramolecular interactions. The position of the fluorine atoms enables temperature-responsive contrast enhancement in the reduced form of the contrast agent and detection of the oxidized contrast agent via MRI in vivo. Positive contrast is observed in 1H-MRI with Eu in the +2 oxidation state, and chemical exchange saturation transfer and 19F-MRI signal are observed with Eu in the +3 oxidation state. Contrast enhancement is controlled by the redox state of Eu, and modulated by the fluorous interactions that cage a bound water molecule reduce relaxivity in a temperature-dependent fashion. Together, these advancements constitute the first report of in vivo, redox-responsive imaging using 19F-MRI.

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

The EuII/III redox couple offers metal-based oxidation-sensing with magnetic resonance imaging making the study of EuII oxidation chemistry important in the design of new probes. Accordingly, we explored oxidation reactions with a set of EuII -containing complexes. Superoxide formation from the reaction between EuII and dioxygen was observed using electron paramagnetic resonance spectroscopy. Additionally, oxidation kinetics of three EuII -containing complexes with bromate and glutathione disulfide at pH values, including 5 and 7, is reported. In the reaction with bromate, the oxidation rate of two of the complexes increased by 7.3 and 6.7 times upon decreasing pH from 7 to 5, but the rate increased by 17 times for a complex containing amide functional groups over the same pH range. The oxidation rate of a fluorobenzo-functionalized cryptate was relatively slow, indicating that the ligand used to impart thermodynamic oxidative stability might also be useful for controlling oxidation kinetics.