Cytotoxic Oligomers and Fibrils Trapped in a Gel‐like State of α‐Synuclein Assemblies

α‐Synuclein (α‐Syn) aggregation is associated with Parkinson's disease (PD) pathogenesis. In PD, the role of oligomers versus fibrils in neuronal cell death is debatable, but recent studies suggest oligomers are a proximate neurotoxin. Herein, we show that soluble α‐Syn monomers undergo a transformation from a solution to a gel state on incubation at high concentration. Detailed characterization of the gel showed the coexistence of monomers, oligomers, and short fibrils. In vitro, the gel was highly cytotoxic to human neuroblastoma cells. The individual constituents of the gel are short‐lived species but toxic to the cells. They comprise a structurally heterogeneous population of α‐helical and β‐sheet‐rich oligomers and short fibrils with the cross‐β motif. Given the recent evidence of the gel‐like state of the protein associated with neurodegenerative diseases, the gel state of α‐Syn in this study represents a mechanistic and structural model for the in vivo toxicity of α‐Syn in PD.     

Bimetallic Ag‐Pt Sub‐nanometer Supported Clusters as Highly Efficient and Robust Oxidation Catalysts

A combined experimental and theoretical investigation of Ag‐Pt sub‐nanometer clusters as heterogeneous catalysts in the CO→CO₂ reaction (COox) is presented. Ag₉Pt₂ and Ag₉Pt₃ clusters are size‐selected in the gas phase, deposited on an ultrathin amorphous alumina support, and tested as catalysts experimentally under realistic conditions and by first‐principles simulations at realistic coverage. In situ GISAXS/TPRx demonstrates that the clusters do not sinter or deactivate even after prolonged exposure to reactants at high temperature, and present comparable, extremely high COox catalytic efficiency. Such high activity and stability are ascribed to a synergic role of Ag and Pt in ultranano‐aggregates, in which Pt anchors the clusters to the support and binds and activates two CO molecules, while Ag binds and activates O₂, and Ag/Pt surface proximity disfavors poisoning by CO or oxidized species.     

Predicting the Surface Tension of Deep Eutectic Solvents: A Step Forward in the Use of Greener Solvents

Deep eutectic solvents (DES) are an important class of green solvents that have been developed as an alternative to toxic solvents. However, the large-scale industrial application of DESs requires fine-tuning their physicochemical properties. Among others, surface tension is one of such properties that have to be considered while designing novel DESs. In this work, we present the results of a detailed evaluation of Quantitative Structure-Property Relationships (QSPR) modeling efforts designed to predict the surface tension of DESs, following the Organization for Economic Co-operation and Development (OECD) guidelines. The data set used comprises a large number of structurally diverse binary DESs and the models were built systematically through rigorous validation methods, including ‘mixtures-out’- and ‘compounds-out’-based data splitting. The most predictive individual QSPR model found is shown to be statistically robust, besides providing valuable information about the structural and physicochemical features responsible for the surface tension of DESs. Furthermore, the intelligent consensus prediction strategy applied to multiple predictive models led to consensus models with similar statistical robustness to the individual QSPR model. The benefits of the present work stand out also from its reproducibility since it relies on fully specified computational procedures and on publicly available tools. Finally, our results not only guide the future design and screening of novel DESs with a desirable surface tension but also lays out strategies for efficiently setting up silico-based models for binary mixtures.     

pH‐Triggered Sustained Drug Delivery from a Polymer Micelle having the β‐Thiopropionate Linkage

The synthesis, micellar aggregation, and pH‐triggered intracellular drug delivery ability of an amphiphilic statistical copolymer (P2) are studied. Two methacrylate derivatives, one containing a hydrophilic pendant and the other containing a hydrophobic pendant chain, are copolymerized to produce P2. The hydrophobic pendant chain is linked to the polymer backbone by a β‐thiopropionate linkage, known to undergo slow hydrolysis at mild acidic pH. P2 forms a multimicellar cluster in water with a critical aggregation concentration of 0.02 mg mL⁻¹ and encapsulates a hydrophobic guest such as pyrene, Nile red, or the anti‐cancer drug doxorubicin (Dox). Sustained release of the entrapped Dox (80% after 100 h) is noticed at pH 5.2, while release is significantly slower (35% after 100 h) at pH 7.4. Acidic hydrolysis of the β‐thiopropionate linkage leading to the reduction of the hydrophobicity is established as the cause for micellar disassembly and triggered drug release. Cell‐culture studies with the human breast cancer cell line, MCF‐7, reveal biocompatibility of P2 (below 150 μg mL⁻¹). It is further tested for intracellular delivery of Dox. MCF‐7 cells remain healthy at pH 7.4 but become unhealthy at pH 5.2 when treated with a Dox‐loaded P2 micelles.

     

Dynamic solvation in imidazolium-based ionic liquids on short time scales

Steady-state and time-resolved Stokes shift data for the probe coumarin 153 in two imidazoles, six imidazolium-based ionic liquids, and several other solvents are presented. These results are consistent with our original suggestion (J. Phys. Chem. B 2004, 108, 10245-10255) that initial solvation is dominated by the organic moiety of the ionic liquid, and they show that for the imidazole-based liquids initial solvation is in all cases very rapid. Solvation by methylimidazole and butylimidazole is complete in 100 ps, and all of the imidazolium ionic liquids demonstrate similarly rapid initial solvation. Owing to the importance of determining the amount of initial solvation that is missed in a given experiment with finite time resolution, we discuss a method of estimating the intramolecular contribution to the reorganization energy. This method yields 2068 cm(-1) and is compared with an alternative method.     

Tolerance Factors of A2ScNbO7 (A3+ = Pr,Nd, Eu,Gd, Dy) Pyrochlore Type Oxide

Crystallography Reports - In this work, we apply the concept of tolerance factors to pyrochlore solid solution, especially when the B-site contains two different ions with different masses (as well...     

Results on L-functions and certain uniqueness questions of Gross

In this paper, we study the value distribution of L-functions in the Selberg class and concentrate on the uniqueness questions of L-functions that share one or two sets with an arbitrary meromorphic function. The results obtained in this paper improve the recent results due to Q.-Q. Yuan, X.-M. Li, and H.-X. Yi [Value distribution of L-functions and uniqueness questions of F. Gross, Lith. Math. J., 58(2):249–262, 2018] and also extend a result due to B.Q. Li [A result on value distribution of L-functions, Proc. Am. Math. Soc., 138(6):2071–2077, 2010].

     

Photophysical Investigations on Determination of Ionicity and Electronic Structures for the Non-covalent Complexes of Calix[4]resorcinarene with Fullerenes C<Subscript>60</Subscript> and C<Subscript>70</Subscript> in the Solution State

Ground state non-covalent interactions between a macrocyclic receptor, C-methylcalix[4]resorcinarene (1) and fullerenes (C₆₀ and C₇₀) have been studied in benzonitrile by an absorption spectrophotometric method. Absorption bands are located in the visible region due to the charge transfer (CT) transition between 1 and various electron acceptors (including fullerenes), namely, 2,3-dichloro-5,6-dicyano-p-benzoquinone, tetracyanoquinodimethane and p-chloranil. Utilizing the CT absorption bands, various important physicochemical parameters, including oscillator strength, resonance energy, transition dipole strength of all the acceptor-1 complexes and vertical ionization potential of 1 are determined. Job’s method of continuous variation reveals 1:1 stoichiometry between fullerenes and 1. The most fascinating feature of the present study is that 1 binds selectively to C₇₀ compared to C₆₀ as obtained from binding constant (K) data of C₆₀-1 (K_C60-1K_{\mathrm{C}60\mbox{-}\mathbf{1}}) and C₇₀-1 (K_C70-1K_{\mathrm{C}70\mbox{-}\mathbf{1}}) complexes, i.e., K_C60-1=190K_{\mathrm{C}60\mbox{-}\mathbf{1}}=190 dm³⋅mol⁻¹ and K_C70-1=5,800K_{\mathrm{C}70\mbox{-}\mathbf{1}}=5{,}800 dm³⋅mol⁻¹ and selectivity (K_C70-1 /K_C60-1 ) ∼30. Quantum chemical calculations based on hybrid density functional theory estimate the enthalpies of formation of the fullerene-1 complexes in vacuo and provide very good support for selectivity in the K values of the C₇₀ and C₆₀ complexes of 1. The exchange and correlation energies have been calculated using a hybrid DFT functional method. We have opted to use the hybrid DFT functional over the Hartree-Fock method, as it can account for correlation effects also. Molecular electrostatic potential map calculations give a clear picture on the electronic structures of the fullerene-1 complexes.