Gadolinium-Decorated Silica Microspheres as Redox-Responsive MRI Probes for Applications in Cell Therapy Follow-Up

The redox microenvironment within a cell graft can be considered as an indicator to assess whether the graft is metabolically active or hypoxic. We present a redox-responsive MRI probe based on porous silica microparticles whose surface has been decorated with a Gd-chelate through a disulphide bridge. Such microparticles are designed to be interspersed with therapeutic cells within a biocompatible hydrogel. The onset of reducing conditions within the hydrogel is paralleled by an increased clearance of Gd, that can be detected by MRI

H5EPTPACH2OH: Synthesis, Relaxometric Characterization and 1H NMR Spectroscopic Studies on the Solution Dynamics of Its LnIII Complexes

The synthesis and characterization of a new metal chelator, 4-(S)-hydroxymethyl-3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid (H5EPTPACH2OH), is reported. Protonation constants for the ligand H5EPTPACH2OH and for the previously reported H5EPTPAC16 have been determined by potentiometry, which reveals that both ligands display slightly higher protonation constants relative to that of the ligand DTPA5-. The stability constant for the [Gd(EPTPACH2OH)(H2O)]2- complex has also been determined by potentiometry. The obtained value (log KGdL = 16.7) is two orders of magnitude lower than that for the [Gd(EPTPA)(H2O)]2- complex, which indicates the destabilizing effect of the pendant hydroxymethyl group at the EPTPA backbone. The microscopic protonation scheme has been deduced from the pH dependence of the 1H NMR spectra of both H5EPTPACH2OH and H5EPTPAC16 ligands. The first two protonations occur exclusively at the backbone nitrogen atoms - the first protonation occurs preferentially at the more basic central nitrogen atom. The second proton distributes preferentially between the two terminal nitrogen atoms with the favoring of the trimethylene nitrogen atom over the ethylene nitrogen atom. The LnIII complexes of the ligand H5EPTPACH2OH have been prepared and their solution dynamics studied by 1H NMR spectroscopy. Two sets of resonances of very different intensities from two isomeric complexes have been observed. Relaxometric investigations (17O NMR and 1H NMRD) demonstrate that the [Gd(EPTPACH2OH)(H2O)]2- complex displays an accelerated water-exchange rate (kex = 87.6 × 106 s-1) that is close to the theoretically derived optimal value. However, the kinetic stability of this complex in phosphate-buffered solutions towards Zn2+ transmetallation is quite low, but higher than that of the corresponding methyl derivative.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007

Metal binding properties of fluorescent analogues of trichogin GA IV: a conformational study by time-resolved spectroscopy and molecular mechanics investigations

The metal ion binding properties of two fluorescent analogues of trichogin GA IV, which is a natural undecapeptide showing significant antimicrobial activity, were studied by circular dichroism, time-resolved optical spectroscopy, and molecular mechanics calculations. Binding of Ca(II) and Gd(III) to the peptides investigated was shown to promote a structural transition from highly helical conformations to folded structures characterized by formation of a loop that embedded the metal ion. Time-resolved spectroscopy revealed that peptide dynamics is also remarkably affected by ion binding: peptide-backbone motions slowed down to the microsecond time scale. Finally, molecular mechanics calculations emphasized the role of the central Gly5-Gly6 motif, which allowed for the twisting of the peptide segment that gave rise to the formation of the binding cavity