Coordination properties of Cu(II) ions towards a phosphorylated fragment from the R1 domain of the tau protein and the effect of Ser phosphorylation on Cu(II) binding affinity.

Tau hyperphosphorylation plays a key role in Alzheimer's disease, mediating tau protein aggregation and deposition as neurofibrillary tangles in the intracellular space of neurons. The potential implications of Cu(II) ions on the disease have been studied intensively, focusing both on Cu(II)-amyloid and on Cu(II)-tau fragment interactions. Nevertheless, there is still a lack of information concerning the metal binding properties and the affinity of phosphorylated fragments of tau. In this work, the coordination properties of Cu(II) ions toward the peptides Ac-GSTENLKH-NH2 (R1) and Ac-GS(P)TENLKH-NH2 (R1P) (Ser phosphorylated analogue) were studied using potentiometric and spectroscopic (vis-EPR) methods. The above sequence belongs to the 261-268 segment of the R1 pseudorepeat of the microtubule-binding domain of the longest tau isoform. It includes both the required metal anchor site (His268) and the residue Ser262, a well-known tau phosphorylation site. There was no surprise in the coordination process of both peptides, which form 1 : 1 metal : ligand complexes and follow the already well-known binding trend (i.e., His imidazole as an anchor site followed by the deprotonation and subsequent coordination of 1-3 amide donors). The additional participation of the Glu-γ-COOH in the equatorial plane was evident for the species detected in acidic solutions, while in the pH range of 7-10, the same group occupies an axial position. The comparison of the Cu(II) binding affinities, revealed that the phosphorylated peptide (R1P) is a more effective ligand than R1 in acidic media. Above pH ∼ 7.9, the order is reversed, highlighting the role of the phosphate inter- or intra-molecular interactions in Cu(II) binding.

Antioxidant Hydrogen-Atom-Transfer to DPPH Radicals by Hybrids of {Hyaluronic-Acid Components}@SiO2.

Hydrogen-atom-transfer (HAT) is among the key mechanisms of antioxidant and antiradical activity in natural systems. Hyaluronic acid (HyA) is currently used extensively in health and cosmetics applications. Herein it is shown that {HyA@SiO2} hybrids based on hyaluronic acid (HyA) components grafted on SiO2 nanoparticles enable significant HAT activity versus DPPH radicals, while the homogeneous HyA counterparts are practically inactive. The {HyA@SiO2} hybrids consist of the two building blocks of HyA [d-glucuronic acid (GLA) and N-acetyl-d-glucosamine (GLAM)] covalently grafted on SiO2 nanoparticles. Based on the kinetic-thermodynamic Arrhenius study, we show that the {SiO2@GLA} hybrids operate spontaneously via hydrogen-atom-transfer (HAT) with a low activation energy barrier, i.e., by ΔΕα ∼ 20 kJ/mol vs the nongrafted counterparts. Moreover, a doubly grafted {GLA@SiO2@GLAM} nanohybrid, i.e. that contains both components of HyA, shows the most significant antioxidant activity. FTIR and Raman analysis reveal that local H-bonding between the SiO2 matrix, GLA, and GLAM in {GLA@SiO2@GLAM} decreases the activation barrier of the HAT mechanism. Thus, {GLA@SiO2@GLAM} nanohybrids exemplify a novel family of materials that are not the mere sum of their components. The present case is the first example of non-phenolic molecules being able to perform antiradical HAT, opening new perspectives not foreseen until today.

Natural Mn-todorokite as an efficient and green azo dye-degradation catalyst.

A natural Mn mineral, i.e., todorokite [(Ca,Na,K)X(Mn4+,Mn3+)6O12·3.5H2O], has been collected in the Apulia region, south of Italy, and evaluated as an oxidation catalyst for the degradation of methyl orange (MO) dye. This Mn-todorokite mineral has been firstly characterized by X-ray diffraction, wavelength-dispersive X-ray fluorescence, BET, scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, and thermogravimetry. Catalytic dye-degradation data show that this Mn-todorokite can operate under strongly oxidizing potentials (Eh > + 400 mV) vs. standard hydrogen electrode performing fast MO degradation (t1/2 < 1 min). A detailed study using electron paramagnetic resonance spectroscopy revealed that, under oxidative conditions (Eh > + 450 mV), the active Mn centers of todorokite evolve rapidly through Mn3+/Mn4+ states and this is correlated with the fast catalytic degradation of MO. These results suggest Mn-todorokite mineral as an efficient, low-cost, and green catalyst which can be used for industrial and environmental purposes.

Interfacial Hydrogen Atom Transfer by nanohybrids based on Humic Acid Like Polycondensates.

Novel nanohybrid materials were prepared by covalent grafting of a polyphenolic polymer [Humic Acid Like Polycondensate (HALP)] on SiO2 nanoparticles. Four nanohybrids were so-produced, using four different types of SiO2 i.e. three Aerosil flame-made nanoparticles with nominal specific surface area of 50, 90 and 300 m(2)/g, herein codenamed OX50, A90, A300 respectively, plus a colloidal SiO2[S300] with SSA=300 m(2)/g. The antioxidant activity of the SiO2-HALP nanohybrids was evaluated by assessing their kinetics for Hydrogen Atom Transfer [HAT] to DPPH radicals. When normalized per same HALP concentration, bigger NPs SiO2[OX50]-HALP NPs can scavenge 280 µmoles of DPPH radicals per gram of HALP, while [A90]-HALP and [A300]-HALP NPs can scavenge 514 and 832 µmoles of DPPH radicals per gram of HALP, respectively. The colloidal SiO2[S300]-HALP can scavenge fewer DPPH radicals (252 µmoles) per gram of HALP. Based on detailed kinetic data it is shown that (i) surface grafted HALPs perform 300% better HAT than non-grafted HALP in solution. (ii) By controlling the particle type and grafting-loading, we can control/optimize the HAT performance: when grafted on the appropriate SiO2 surface the HALP macromolecules are able to quench up to 0.8 mmoles of DPPH-radical per gram of HALP.