Abnormal proteins, influenced by reactive oxygen species (ROS), are directly related to the development of various diseases.

We report a facile synthesis of superparamagnetic CoFe 2 O 4 nanostructures with the assistance of an amino acid (lysine). Monodisperse CoFe 2 O 4 nanospheres and nanoparticles were obtained by adjusting the synthesis parameters (such as the molar ratio of reactants and the solvent). The samples were characterized through scanning electron microscopy, transmission electron microscopy, X-ray diffraction, thermogravimetric analysis, and Fourier-transform infrared spectroscopy. The magnetic property and measured zeta potential shows that both CoFe 2 O 4 nanostructures were superparamagnetic and positively charged. The adsorption performance of the CoFe 2 O 4 nanostructures was evaluated using different dyes, namely, methylene blue, Congo red, Acid Blue 80, methyl orange, rhodamine B, and Cationic red X-GTL, as models. The results show that CoFe 2 O 4 nanospheres consisting of nanoparticles display high adsorption performance on methylene blue, methyl orange, and Congo red, whereas CoFe 2 O 4 nanoparticles prefer adsorbing rhodamine B and Congo red. Therefore, the tunable synthesis of superparamagnetic CoFe 2 O 4 nanostructures provides promising applications for the selective and highly efficient removal of various organic contaminants from industrial effluents.

The aggregation of amyloid-β (Aβ) peptide induced by Cu(2+) is a key factor in development of Alzheimer's disease (AD), and metal ion chelation therapy enables treatment of AD. Three CQi (i = 1, 2, and 3 with R = H, Cl, and NO2, respectively) drugs had been verified experimentally to be much stronger inhibitors than the pioneer clioquinol (CQ) in both disaggregation of Aβ40 aggregate and reduction of toxicity induced by Cu(2+) binding at low pH. Due to the multiple morphologies of Cu(2+)-Aβ40 complexes produced at different pH states, we performed a series of molecular dynamics simulations to explain the structural changes and morphology characteristics as well as intrinsic disaggregation mechanisms of three Cu(2+)-Aβ40 models in the presence of any of the three CQi drugs at both low and high pH states. Three inhibition mechanisms for CQi were proposed as "insertion", "semi-insertion", and "surface" mechanisms, based on the morphologies of CQi-model x (CQi-x, x = 1, 2, and 3) and the strengths of binding between CQi and the corresponding model x. The insertion mechanism was characterized by the morphology with binding strength of more than 100 kJ/mol and by CQi being inserted or embedded into the hydrophobic cavity of model x. In those CQi-x morphologies with lower binding strength, CQi only attaches on the surface or inserts partly into Aβ peptide. Given the evidence that the binding strength is correlated positively with the effectiveness of drug to inhibit Aβ aggregation and thus to reduce toxicity, the data of binding strength presented here can provide a reference for one to screen drugs. From the point of view of binding strength, CQ2 is the best drug. Because of the special role of Asp23 in both Aβ aggregation and stabilizing the Aβ fibril, the generation of a H-bond between CQ3 and Asp23 of the Aβ40 peptide is believed to be responsible for CQ3 having the strongest disaggregation capacity. Therefore, besides strong binding, stronger propensity to H-bond with Asp23 would be another key factor to be taken seriously into account in drug screens. Meanwhile, the structural characteristics of drug CQi itself are also worthy of attention. First, the increasing polarity from CQ1 and CQ2 to CQ3 in turn results in increasing probability and strength of the interaction between the drug and the N-terminal (NT) region of Aβ40, which obviously inhibits Aβ peptide aggregation induced by Cu(2+) binding. Second, both the benzothiazole ring and phenol ring of CQi can overcome the activation energy barrier (∼16 kJ/mol) to rotate flexibly around the intramolecular C7-N14 bond to achieve the maximum match and interaction with the ambient Aβ40 residues. Such a structural feature of CQi paves the new way for ones in selection and modification of a drug.

Amyloid-β (Aβ/Aβ) peptide with a length of 40 or 42 residues is naturally secreted as cleavage product of the amyloid precursor protein, and formation of Aβ aggregates in a patient's brain is a hallmark of Alzheimer's disease (AD). Therefore, disaggregation and disruption provide potential therapeutic approaches to reduce, inhibit, and even reverse Aβ aggregation. The disaggregation/inhibition effect of the inhibitors applies generally to both Aβ and Aβ aggregations. Here we capture the atomic-level details of the interaction between Aβ/Aβ and either natural tanshinone compound TS1 or its derivative TS0, and observe novel results by using molecular dynamics simulations. We observe that the natural TS1 indeed inhibits the monomolecular Aβ (mAβ) aggregation and disaggregates Aβ amyloid fibrils, being in good agreement with the experimental results. TS1 is favorable to stabilize mAβ and even Aβ fibril, playing an opposite role to that in the Aβ counterpart, however. TS0 can inhibit the misfolding of either mAβ or mAβ and disaggregate Aβ fibril but stabilize the Aβ fibril. Using a combination of secondary structural analysis, MM-PBSA binding energy calculations, and radial distribution functions computations, we find that both TS0 and TS1, especially the former, prefer to bind at the charged residues within disordered N-terminus with a scarce positive binding energy and disappear the characteristic C-terminal bend region of Aβ fibril, as well as twist the Aβ fibril seriously. It turns out to destabilize the Aβ fibril and enable the conversion of U-shaped Aβ fibril from the onefold to the twofold morphologies. The N-terminal binding preference helps us to identify N-terminal region as the specific epitope for specific inhibitors/drugs (such as TS0 and analogues), heralding unusual inhibition/disaggregation or stabilization mechanisms, and offering an alternative direction in engineering new inhibitors to treat AD.

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