Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area.

We report herein a Pt(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectroscopy (XANES) on dried drug-preincubated tumor cell samples revealed a gradual release of cisplatin from the Pt-Mnz prodrug instead of rapid intracellular degradation. The ability of the prodrug to penetrate into three-dimensional (3D) spheroid cellular cultures was evaluated by a novel electrochemical assay via a platinum-coated carbon nanoelectrode, capable of single-cell measurements. Using a unique technique of electrochemical measurements in single tumor spheroids, we were able to both detect the real-time response of the axial ligand to hypoxia and establish the depth of penetration of the drug into the tumor model.

XANES Measurements for Studies of Adsorbed Protein Layers at Liquid Interfaces.

X-ray absorption near edge structure (XANES) spectra for protein layers adsorbed at liquid interfaces in a Langmuir trough have been recorded for the first time. We studied the parkin protein (so-called E3 ubiquitin ligase), which plays an important role in pathogenesis of Parkinson disease. Parkin contains eight Zn binding sites, consisting of cysteine and histidine residues in a tetracoordinated geometry. Zn K-edge XANES spectra were collected in the following two series: under mild radiation condition of measurements (short exposition time) and with high X-ray radiation load. XANES fingerprint analysis was applied to obtain information on ligand environments around zinc ions. Two types of zinc coordination geometry were identified depending on X-ray radiation load. We found that, under mild conditions, local zinc environment in our parkin preparations was very similar to that identified in hemoglobin, treated with a solution of ZnCl2 salt. Under high X-ray radiation load, considerable changes in the zinc site structure were observed; local zinc environment appeared to be almost identical to that defined in Zn-containing enzyme alkaline phosphatase. The formation of a similar metal site in unrelated protein molecules, observed in our experiments, highlights the significance of metal binding templates as essential structural modules in protein macromolecules.

The Influence of Cu and Al Additives on Reduction of Iron(III) Oxide: In Situ XRD and XANES Study.

The reduction of Fe-based nanocomposite catalysts doped with Al and Cu has been studied using in situ X-ray diffraction (XRD), in situ X-ray absorption near-edge structure (XANES), and temperature-programmed reduction (TPR) techniques. The catalysts have been synthesized by melting of iron, aluminum, and copper salts. According to XRD, the catalysts consist mainly of Fe2O3 and Al2O3 phases. Alumina is in an amorphous state, whereas iron oxide forms nanoparticles with the protohematite structure. The Al3+ cations are partially dissolved in the Fe2O3 lattice. Due to strong alumina-iron oxide interaction, the specific surface area of the catalysts increases significantly. TPR and XANES data indicate that copper forms highly dispersed surface CuO nanoparticles and partially dissolves in iron oxide. It has been shown that the reduction of iron(III) oxide by CO proceeds via two routes: a direct two-stage reduction of iron(III) oxide to metal (Fe2O3 → Fe3O4 → Fe) or an indirect three-stage reduction with the formation of FeO intermediate phases (Fe2O3 → Fe3O4 → FeO → Fe). The introduction of Al into Fe2O3 leads to a decrease in the rate for all reduction steps. In addition, the introduction of Al stabilizes small Fe3O4 particles and prevents further sintering of the iron oxide. The mechanism of stabilization is associated with the formation of Fe3- xAl xO4 solid solution. The addition of copper to the Fe-Al catalyst leads to the formation of highly dispersed CuO particles on the catalyst surface and a mixed oxide with a spinel-type crystalline structure similar to that of CuFe2O4. The low-temperature reduction of Cu2+ to Cu0 accelerates the Fe2O3 → Fe3O4 and FeO → Fe transformations but does not affect the Fe3O4 → FeO/Fe stages. These changes in the reduction properties significantly affect the catalytic performance of the Fe-based nanocomposite catalysts in the low-temperature oxidation of CO.

Design of Nickel-Based Cation-Disordered Rock-Salt Oxides: The Effect of Transition Metal (M = V, Ti, Zr) Substitution in LiNi0.5M0.5O2 Binary Systems.

Cation-disordered oxides have been ignored as positive electrode material for a long time due to structurally limited lithium insertion/extraction capabilities. In this work, a case study is carried out on nickel-based cation-disordered Fm3 ̅m LiNi0.5M0.5O2 positive electrode materials. The present investigation targets tailoring the electrochemical properties for nickel-based cation-disordered rock-salt by electronic considerations. The compositional space for binary LiM+3O2 with metals active for +3/+4 redox couples is extended to ternary oxides with LiA0.5B0.5O2 with A = Ni2+ and B = Ti4+, Zr4+, and V+4 to assess the impact of the different transition metals in the isostructural oxides. The direct synthesis of various new unknown ternary nickel-based Fm3̅ m cation-disordered rock-salt positive electrode materials is presented with a particular focus on the LiNi0.5V0.5O2 system. This positive electrode material for Li-ion batteries displays an average voltage of ∼2.55 V and a high discharge capacity of 264 mAhg-1 corresponding to 0.94 Li. For appropriate cutoff voltages, a long cycle life is achieved. The charge compensation mechanism is probed by XANES, confirming the reversible oxidation and reduction of V4+/V5+. The enhancement in the electrochemical performances within the presented compounds stresses the importance of mixed cation-disordered transition metal oxides with different electronic configuration.