Seeking for Innovation with Magnetic Resonance Imaging Paramagnetic Contrast Agents: Relaxation Enhancement via Weak and Dynamic Electrostatic Interactions with Positively Charged Groups on Endogenous Macromolecules.

Gd-L1 is a macrocyclic Gd-HPDO3A derivative functionalized with a short spacer to a trisulfonated pyrene. When compared to Gd-HPDO3A, the increased relaxivity appears to be determined by both the higher molecular weight and the occurrence of an intramolecularly catalyzed prototropic exchange of the coordinated OH moiety. In water, Gd-L1 displayed a relaxivity of 7.1 mM-1 s-1 (at 298 K and 0.5 T), slightly increasing with the concentration likely due to the onset of intermolecular aggregation. A remarkably high and concentration-dependent relaxivity was measured in human serum (up to 26.5 mM-1 s-1 at the lowest tested concentration of 0.005 mM). The acquisition of 1H-nuclear magnetic relaxation dispersion (NMRD) and 17O-R2 vs T profiles allowed to get an in-depth characterization of the system. In vitro experiments in the presence of human serum albumin, γ-globulins, and polylysine, as well as using media mimicking the extracellular matrix, provided strong support to the view that the trisulfonated pyrene fosters binding interactions with the exposed positive groups on the surface of proteins, responsible for a remarkable in vivo hyperintensity in T1w MR images. The in vivo MR images of the liver, kidneys, and spleen showed a marked contrast enhancement in the first 10 min after the i.v. injection of Gd-L1, which was 2-6-fold higher than that for Gd-HPDO3A, while maintaining a very similar excretion behavior. These findings may pave the way to an improved design of MRI GBCAs, for the first time, based on the setup of weak and dynamic interactions with abundant positive groups on serum and ECM proteins.

Fe(deferasirox)2: An Iron(III)-Based Magnetic Resonance Imaging T1 Contrast Agent Endowed with Remarkable Molecular and Functional Characteristics.

The search for alternatives to Gd-containing magnetic resonance imaging (MRI) contrast agents addresses the field of Fe(III)-bearing species with the expectation that the use of an essential metal ion may avoid the issues raised by the exogenous Gd. Attention is currently devoted to highly stable Fe(III) complexes with hexacoordinating ligands, although they may lack any coordinated water molecule. We found that the hexacoordinated Fe(III) complex with two units of deferasirox, a largely used iron sequestering agent, owns properties that can make it a viable alternative to Gd-based agents. Fe(deferasirox)2 displays an outstanding thermodynamic stability, a high binding affinity to human serum albumin (three molecules of complex are simultaneously bound to the protein), and a good relaxivity that increases in the range 20-80 MHz. The relaxation enhancement is due to second sphere water molecules likely forming H-bonds with the coordinating phenoxide oxygens. A further enhancement was observed upon the formation of the supramolecular adduct with albumin. The binding sites of Fe(deferasirox)2 on albumin were characterized by relaxometric competitive assays. Preliminary in vivo imaging studies on a tumor-bearing mouse model indicate that, on a 3 T MRI scanner, the contrast ability of Fe(deferasirox)2 is comparable to the one shown by the commercial Gd(DTPA) agent. ICP-MS analyses on blood samples withdrawn from healthy mice administered with a dose of 0.1 mmol/kg of Fe(deferasirox)2 showed that the complex is completely removed in 24 h.

Liposome-Based Bioassays.

This review highlights the potential of using liposomes in bioassays. Liposomes consist of nano- or micro-sized, synthetically constructed phospholipid vesicles. Liposomes can be loaded with a number of reporting molecules that allow a dramatic amplification of the detection threshold in bioassays. Liposome-based sensors bind or react with the biological components of targets through the introduction of properly tailored vectors anchored on their external surface. The use of liposome-based formulations allows the set-up of bioassays that are rapid, sensitive, and often suitable for in-field applications. Selected applications in the field of immunoassays, as well as recognition/assessment of corona proteins, nucleic acids, exosomes, bacteria, and viruses are surveyed. The role of magnetoliposomes is also highlighted as an additional tool in the armory of liposome-based systems for bioassays.

Cooperative Iodide Pd(0)-Catalysed Coupling of Alkoxyallenes and N-Tosylhydrazones: A Selective Synthesis of Conjugated and Skipped Dienes.

Palladium(0)-catalysed hydro-alkylation or -alkenylation of alkoxyallenes with N-tosylhydrazones gives direct access to conjugated and skipped 1-alkoxydienes with high efficiency and excellent functional-group compatibility. The reaction is proposed to involve the in situ-formed t-butanol as proton source in the key step of the allylpalladium(II) species generation. Moreover, lithium iodide or iodobenzene are employed as an unprecedented iodide (I- ) reservoir to sustain the catalytic cycle.