Surprising Complexity of the [Gd(AAZTA)(H2O)2]− Chelate Revealed by NMR in the Frequency and Time Domains

[Abstract] Typically, Ln(III) complexes are isostructural along the series, which enables studying one particular metal chelate to derive the structural features of the others. This is not the case for [Ln(AAZTA)(H2O)x]− (x = 1, 2) systems, where structural variations along the series cause changes in the hydration number of the different metal complexes, and in particular the loss of one of the two metal-coordinated water molecules between Ho and Er. Herein, we present a 1H field-cycling relaxometry and 17O NMR study that enables accessing the different exchange dynamics processes involving the two water molecules bound to the metal center in the [Gd(AAZTA)(H2O)2]− complex. The resulting picture shows one Gd-bound water molecule with an exchange rate ∼6 times faster than that of the other, due to a longer metal–water distance, in accordance with density functional theory (DFT) calculations. The substitution of the more labile water molecule with a fluoride anion in a diamagnetic-isostructural analogue of the Gd-complex, [Y(AAZTA)(H2O)2]−, allows us to follow the chemical exchange process by high-resolution NMR and to describe its thermodynamic behavior. Taken together, the variety of tools offered by NMR (including high-resolution 1H, 19F NMR as a function of temperature, 1H longitudinal relaxation rates vs B0, and 17O transverse relaxation rates vs T) provides a complete description of the structure and exchange dynamics of these Ln-complexes along the series.This research was supported by the Università del Piemonte Orientale (Ricerca locale FAR2019). F.C., L.T., and M.B. acknowledge the financial support from the Ministero dell’Università e della Ricerca (PRIN 2017A2KEPL project “Rationally designed nanogels embedding paramagnetic ions as MRI probes”). This work was carried out within the framework of the COST CA15209 Action “European Network on NMR Relaxometry”Italia. Ministero dell'Università e della Ricerca; PRIN-2017A2KEP

Characterization of the Fe(III)-Tiron System in Solution through an Integrated Approach Combining NMR Relaxometric, Thermodynamic, Kinetic, and Computational Data

The Fe(III)-Tiron system (Tiron = 4,5-dihydroxy1,3-benzenedisulfonate) was investigated using a combination of 1H and 17O NMR relaxometric studies at variable field and temperature and theoretical calculations at the DFT and NEVPT2 levels. These studies require a detailed knowledge of the speciation in aqueous solution at different pH values. This was achieved using potentiometric and spectrophotometric titrations, which afforded the thermodynamic equilibrium constants characterizing the Fe(III)-Tiron system. A careful control of the pH of the solution and the metal-to-ligand stoichiometric ratio allowed the relaxometric characterization of [Fe(Tiron)3]9-, [Fe(Tiron)2(H2O)2]5-, and [Fe(Tiron)(H2O)4]- complexes. The 1H nuclear magnetic relaxation dispersion (NMRD) profiles of [Fe(Tiron)3]9- and [Fe(Tiron)2(H2O)2]5- complexes evidence a significant second-sphere contribution to relaxivity. A complementary 17O NMR study provided access to the exchange rates of the coordinated water molecules in [Fe(Tiron)2(H2O)2]5- and [Fe(Tiron)(H2O)4]- complexes. Analyses of the NMRD profiles and NEVPT2 calculations indicate that electronic relaxation is significantly affected by the geometry of the Fe3+ coordination environment. Dissociation kinetic studies indicated that the [Fe(Tiron)3]9- complex is relatively inert due to the slow release of one of the Tiron ligands, while the [Fe(Tiron)2(H2O)2]5- complex is considerably more labile

Controlling Water Exchange Rates in Potential Mn²⁺-Based MRI Agents Derived From NO2A²⁻

[Abstract] We report a series of pentadentate ligands based on a 1,4,7-triazacyclononane-1,4-diacetic acid (H2NO2A) containing different substituents attached to the third nitrogen atom of the macrocyclic unit. Detailed 1H Nuclear Magnetic Relaxation Dispersion (NMRD) characterisation of the corresponding Mn2+ complexes suggests the formation of six-coordinate species in solution containing an inner-sphere water molecule. This was confirmed by recording the transverse 17O relaxation time and chemical shift measurements. The water exchange rate of the coordinated water molecule was found to be strongly influenced by the nature of the substituent R at position 7 of the triazacyclononane unit (R = Me, k298ex = 62.6 × 107 s−1; R = Bz, k298ex = 4.4 × 107 s−1; R = 1-phenylethyl, k298ex = 2.6 × 107 s−1). The decreasing exchange rates are explained by the increasing bulkiness of the substituent, which hinders the approach of the entering water molecule in an associatively activated water exchange mechanism. This is supported by DFT calculations (M062X/TZVP), which confirm the associative nature of the water exchange reaction. A potentially decadentate ligand containing two NO2A units linked by a xylenyl spacer in the meta position was also synthesised. The corresponding binuclear Mn2+ complex contains two metal ions with different hydration numbers, as evidenced by 1H NMRD and 17O NMR measurements. DFT calculations show that this is related to the presence of a bridging bidentate μ–η1-carboxylate group connecting the two metal centers. The results reported in this work provide a straightforward strategy to control the exchange rate of the coordinated water molecule in this family of MRI contrast agent candidates.Authors R. P.-P., I. B., E. I., C. P.-I. and D. E.-G. thank Ministerio de Economía y Competitividad (CTQ2016-76756-P) and Xunta de Galicia (ED431B 2017/59 and ED431D 2017/01) for generous financial support and Centro de Supercomputación of Galicia (CESGA) for providing the computer facilities. R. P.-P. thanks Ministerio de Economía y Competitividad for a PhD FPI grant (BES-2014-068399) and a fellowship for a short term stay in Alessandria (EEBB-I-18-13075). M. B. and F. C. are grateful to Università del Piemonte Orientale for financial support (Ricerca locale 2016). This work was carried out within the framework of the COST CA15209 Action "European Network on NMR Relaxometry"Xunta de Galicia; ED431B 2017/59Xunta de Galicia; ED431D 2017/0

1H NMR Relaxometric Study of Chitosan-Based Nanogels Containing Mono- and Bis-Hydrated Gd(III) Chelates: Clues for MRI Probes of Improved Sensitivity

Hydrogel nanoparticles composed of chitosan and hyaluronate and incorporating Gd-based MRI contrast agents with different hydration number (e.g., [Gd(DOTA)(H2O)]− and [Gd(AAZTA)(H2O)2]−) were prepa..

Bispyrene Functionalization Drives Self-Assembly of Graphite Nanoplates into Highly Efficient Heat Spreader Foils

Thermally conductive nanopapers fabricated from graphene and related materials are currently showing great potential in thermal management applications. However, thermal contacts between conductive plates represent the bottleneck for thermal conductivity of nanopapers prepared in the absence of a high temperature step for graphitization. In this work, the problem of ineffective thermal contacts is addressed by the use of bifunctional polyaromatic molecules designed to drive self-assembly of graphite nanoplates (GnP) and establish thermal bridges between them. To preserve the high conductivity associated to a defect-free sp2 structure, non-covalent functionalization with bispyrene compounds, synthesized on purpose with variable tethering chain length, was exploited. Pyrene terminal groups granted for a strong pi-pi interaction with graphene surface, as demonstrated by UV-Vis, fluorescence, and Raman spectroscopies. Bispyrene molecular junctions between GnP were found to control GnP organization and orientation within the nanopaper, delivering significant enhancement in both in-plane and cross-plane thermal diffusivities. Finally, nanopapers were validated as heat spreader devices for electronic components, evidencing comparable or better thermal dissipation performance than conventional Cu foil, while delivering over 90% weight reduction

Dimer formation of GdDO3A-arylsulfonamide complexes causes loss of pH-dependency of relaxivity

[Abstract] Gadolinium(III) complexes with pH-dependent relaxivities have been proposed as responsive magnetic resonance imaging (MRI) contrast agents (CA) for mapping of pH value in living subjects. The latter is clinically relevant because hypoxia-induced reduction of interstitial pH (acidosis) is a hallmark of tumor progression and resistance against chemotherapy. In order to obtain versatile building blocks for integration of a pH-responsive MRI-CA functionality into larger molecular assemblies, such as bioconjugates, micelles or nanoparticles, we equipped the structural motif GdDO3A-ethylene(arylsulfonic acid) with additional carboxylic acid moieties in the aromatic para-position. Two novel compounds were characterized concerning their pH-dependent relaxivity as well as by 17O NMR and 1H NMRD, augmented by determination of luminescence lifetimes of the respective Eu(III) complexes and structural modelling by density functional theory (TPSSh/LCRECP/6-31G(d)). Unexpected involvement of the peripheral carboxylates into metal ion complexation effected self-assembly of the lanthanide(III) complexes, resulting in dimeric species comprising two lanthanide ions, two symmetrically bridging ligands, and one coordinated water molecule per Gd(III) (q = 1). These structures are stable even at low concentrations and in presence of competing anions like phosphate. The pH-sensitive sulfonamide moieties are not involved into Gd(III) coordination, resulting in virtually constant relaxivities of r1 = 6.7 mM−1 s−1 (298 K, 20 MHz) over the biologically relevant pH range (4 to 9). Since further functionalisation on the peripheral carboxylates would effectively inhibit dimer formation, the compounds are nonetheless suited for the initially envisaged field of application.Lorenzo Tei sincerely acknowledges the Alexander von Humboldt Foundation (AvH) for a Research fellowship. The authors also thank Dr. Claudio Cassino for the help in acquisition of 1H NMR DOSY spectra, and the Deutsche Forschungsgemeinschaft (CRC 824) for suppor

tungsten oxide a catalyst worth studying for the abatement and decontamination of chemical warfare agents

AbstractTungsten(VI) oxide, WO3, was studied and used as a heterogeneous catalyst for the liquid-phase oxidative abatement and solid-phase decontamination of simulants of chemical warfare agents, CWAs. The catalytic performance of WO3 was compared to the one of a soluble W-containing model catalyst, W(IV)-heptaisobutyl polyhedral oligomeric silsesquioxane, W-POSS. In liquid-phase abatement tests, WO3 promoted a complete degradation of the toxic agent simulant within 24 h, in the presence of aqueous hydrogen peroxide, at room temperature. In solid-phase decontamination tests, when WO3 was mixed with sodium perborate as a solid oxidant, it was also tested in the decontamination of a cotton textile support from organosulfide and organophosphonate agents (simulants of blistering and nerve CWAs, respectively), showing promising performances comparable to, or sometimes better than, a nanostructured TiO2 catalyst, taken as a reference material. The environmental impact of the WO3 catalyst was assessed on biolumi..