Search

Lanthanide complexes of DO3A‐derivative ligands bearing a pyridine‐carbamate (L1) or pyridine‐amine (L2) arm have potential interest in the design of enzymatically activated imaging probes. Solid‐state X‐ray structures for CeL1 and YbL2 both demonstrate twisted square antiprismatic geometry, with the metal ion in a nine‐ or an eight‐coordinate environment, respectively. As assessed by pH‐potentiometry, in solution lanthanide ions form more stable complexes with the nonadentate L1 than with the octadentate L2 ligand (logKML=18.7–21.1 vs. 16.7–18.6, respectively), while stability constants are similar for L1 and L2 chelates of Mg2+, Ca2+, Zn2+ or Cu2+. The kinetic inertness of GdL1 is exceptionally high, with an estimated dissociation half‐life of ~108 h at pH 7.4, while LnL2 (Ln=Ce, Gd, Yb) complexes have 3–4 orders of magnitude faster dissociation, related to the presence of the protonatable, non‐coordinating amine function. The water exchange rate determined for the monohydrated GdL2 (kex298=1.3×106 s−1) shows a threefold decrease with respect to GdDOTA, as a consequence of a reduction in the negative charge and in the steric crowding around the water binding site, both important in dissociatively activated water exchange processes. [ABSTRACT FROM AUTHOR]

This study describes the incorporation of bioengineered flagellin (4HIS) protein in conjunction with TiO2 anatase nanoparticles into a chitosan (Chit) polymeric matrix as a highly sensitive electrode modifier for the determination of diclofenac sodium (DS) in wastewater. Two types of electrodes were prepared using a simple drop-casting method. The inner structure of the obtained modified electrode was characterized by scanning electron microscopy (SEM) in combination with energy-dispersive X-ray spectroscopy and isothermal titration calorimetry (ITC). The electrochemical and electroanalytical parameters of DS oxidation at the nanostructured interface of the modified electrode were obtained via cyclic voltammetry and square-wave voltammetry. The analytical parameters for diclofenac electro-detection showed a 50% decrease in LOD and LOQ at Chit + TiO2 + 4HIS/GCE-modified electrode compared with the Chit + 4HIS/GCE-modified electrode. The obtained tools were successfully used for DS detection in drug tablets and wastewater samples. Thus, it was demonstrated that in the presence of a histidine-containing flagellin variant, the electrode has DS recognition capacity which increases in the presence of TiO2 nanoparticles, and both induce excellent performances of the prepared tools, either in synthetic solution or in real samples. [ABSTRACT FROM AUTHOR]

A series of 2-iodo-1-C-substituted glycals having electron withdrawing groups (CN, CO2CH3, CONH2) at the C-1 carbon were synthesized from the parent 1-C-substituted glycals using N-iodosuccinimide or N-iodophtalimide and a Lewis acid. The utility of the iodoglycal derivatives has been demonstrated by Suzuki–Miyaura coupling reactions with aromatic and aliphatic boronic acids to give 1,2-C,C-disubstituted glycals in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

We present the in vitro characterisation of a Gd3+-based contrast agent that responds to Zn2+ upon interaction with Human Serum Albumin. We show that the contradictory in vivo behaviour is related to Gd3+-accumulation in Zn-rich tissues. This highlights the importance of the biodistribution of such contrast agents. [ABSTRACT FROM AUTHOR]

Mn2+ complexes of 2,4‐pyridyl‐disubstituted bispidine ligands have emerged as more biocompatible alternatives to Gd3+‐based MRI probes. They display relaxivities comparable to that of commercial contrast agents and high kinetic inertness, unprecedented for Mn2+ complexes. The chemical structure, in particular the substituents on the two macrocyclic nitrogens N3 and N7, are decisive for the conformation of the Mn2+ complexes, and this will in turn determine their thermodynamic, kinetic and relaxation properties. We describe the synthesis of four ligands with acetate substituents in positions N3, N7 or both. We evidence that the bispidine conformation is dependent on N3 substitution, with direct impact on the thermodynamic stability, kinetic inertness, hydration state and relaxivity of the Mn2+ complexes. These results unambiguously show that (i) solely a chair‐chair conformation allows for favorable inertness and relaxivity, and (ii) in this family such chair‐chair conformation is accessible only for ligands without N3‐appended carboxylates. [ABSTRACT FROM AUTHOR]

A new fluorinated manganese porphyrin, (Mn‐TPP‐p‐CF3) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual 1H relaxivity and 19F NMR response to redox changes. The physical‐chemical characterization of both redox states in DMSO‐d6/H2O evidenced that the 1H relaxometric and 19F NMR properties are appropriate for differential redox MRI detection. The Mn(III)‐F distance (dMn−F=9.7–10 Å), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on 19F T1 and T2 relaxation times. Mn‐TPP‐p‐CF3 has a reversible Mn(II)/Mn(III) redox potential of 0.574 V vs. NHE in deoxygenated aqueous HEPES/ THF solution. The reduction of Mn(III)‐TPP‐p‐CF3 in the presence of ascorbic acid is slowly, but fully reversed in the presence of air oxygen, as monitored by UV‐Vis spectrometry and 19F NMR. The broad 1H and 19F NMR signals of Mn(III)‐TPP‐p‐CF3 disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened 19F NMR signal from Mn(II)‐TPP‐p‐CF3. Phantom 19F MR images in DMSO show a MRI signal intensity decrease upon reduction of Mn(III)‐TPP‐p‐CF3, retrieved upon complete reoxidation in air within ~24 h. 1H NMRD curves of the Mn(III)/(II)‐TPP‐p‐CF3 chelates in mixed DMSO/water solvent have the typical shape of Mn(II)/Mn(III) porphyrins. [ABSTRACT FROM AUTHOR]

A new 15-membered pyridine-based macrocyclic ligand containing one acetate pendant arm (N-carboxymethyl-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1(18),14,16-triene, L1) was synthesized and its Mn(II) complex MnL1 was investigated in the context of MRI contrast agent development. The X-ray molecular structure of MnL1 confirmed a coordination number of seven with an axially compressed pentagonal bipyramidal geometry and one coordination site available for an inner-sphere water molecule. The protonation constants of L1 and the stability constants of Mn(II), Zn(II), Cu(II) and Ca(II) complexes were determined by potentiometry, and revealed higher thermodynamic stabilities in comparison with complexes of 15-pyN3O2, the parent macrocycle without an acetate pendant arm. The MnL1 complex is fully formed at physiological pH 7.4, but it shows fast dissociation kinetics, as followed by relaxometry in the presence of an excess of Zn(II). The short dissociation half-life estimated for physiological pH (ca. 3 minutes) is related to fast spontaneous dissociation of the non-protonated complex. At lower pH values, the proton-assisted dissociation pathway becomes important, while the Zn(II) concentration has no effect on the dissociation rate. 17O NMR and 1H NMRD data indicated the presence of one inner-sphere water molecule with a rather slow exchange (k 298ex = 4.5 × 106 s−1) and provided information about other microscopic parameters governing relaxation. The relaxivity (r1 = 2.45 mM−1 s−1 at 20 MHz, 25 °C) corresponds to typical values for monohydrated Mn(II) chelates. Overall, the acetate pendant arm in L1 has a beneficial effect with respect to 15-pyN3O2 in increasing the thermodynamic stability and kinetic inertness of its Mn(II) complex, but leads to a reduced number of inner-sphere water molecules and thus lower relaxivity. [ABSTRACT FROM AUTHOR]