Deconvoluting binding sites in amyloid nanofibrils using time-resolved spectroscopy

Steady-state fluorescence spectroscopy has a central role not only for sensing applications, but also in biophysics and imaging. Light switching probes, such as ruthenium dipyridophenazine complexes, have been used to study complex systems such as DNA, RNA, and amyloid fibrils. Nonetheless, steady-state spectroscopy is limited in the kind of information it can provide. In this paper, we use time-resolved spectroscopy for studying binding interactions between amyloid-β fibrillar structures and photoluminescent ligands. Using time-resolved spectroscopy, we demonstrate that ruthenium complexes with a pyrazino phenanthroline derivative can bind to two distinct binding sites on the surface of fibrillar amyloid-β, in contrast with previous studies using steady-state photoluminescence spectroscopy, which only identified one binding site for similar compounds. The second elusive binding site is revealed when deconvoluting the signals from the time-resolved decay traces, allowing the determination of dissociation constants of 3 and 2.2 μM. Molecular dynamic simulations agree with two binding sites on the surface of amyloid-β fibrils. Time-resolved spectroscopy was also used to monitor the aggregation of amyloid-β in real-time. In addition, we show that common polypyridine complexes can bind to amyloid-β also at two different binding sites. Information on how molecules bind to amyloid proteins is important to understand their toxicity and to design potential drugs that bind and quench their deleterious effects. The additional information contained in time-resolved spectroscopy provides a powerful tool not only for studying excited state dynamics but also for sensing and revealing important information about the system including hidden binding sites.

Deconvolution of binding equilibrium data measured by time-resolved spectroscopy revealed two binding sites of a ruthenium complex when bound to amyloid-β fibrils: one elongated the lifetime of ruthenium complex and the other did not affect its lifetime.     

Self-organization of two-dimensional waves in an active dispersive-dissipative nonlinear medium

We consider the pattern-formation dynamics of a two-dimensional (2D) nonlinear evolution equation that includes the effects of instability, dissipation, and dispersion. We construct 2D stationary solitary pulse solutions of this equation, and we develop a coherent structures theory that describes the weak interaction of these pulses. We show that in the strongly dispersive case, 2D pulses organize themselves into V shapes. Our theoretical findings are in good agreement with time-dependent computations of the fully nonlinear system.     

Density functional theory study of the oxidation reaction in the gas and aqueous phase of allyl methyl disulfide with hydroxyl radical

Structural Chemistry - An in silico analysis of the oxidation mechanism of allyl methyl disulfide (AMDS) by hydroxyl radical was achieved at DFT level using B3LYP, CAM-B3LYP, M06-2X, and BMK...     

Proton Affinities of Cationic Carbone Adducts [AC(PPh3)2]+ (A=Halogen,Hydrogen, Methyl) and Unusual Electronic Structures of the Cations and Dications [AC(H)(PPh3)2]2+

This work reports the syntheses and the first crystal structures of the cationic carbone adducts [FC(PPh₃)₂]⁺ and [BrC(PPh₃)₂]⁺ and the protonated dication [FC(H)(PPh₃)₂]²⁺, which are derived from the carbone C(PPh₃)₂. Quantum chemical calculations and bonding analyses were carried out for the series of cations [AC(PPh₃)₂]⁺ and dications [AC(H)(PPh₃)₂]²⁺, where A=H, Me, F, Cl, Br, I. The bonding analysis suggests that the cations are best described as phosphane complexes L→(CA)⁺←L (L=PPh₃), which are related to the neutral borylene adducts L→(BA)←L (L=cyclic carbene; A=H, aryl) that were recently isolated. The carbone adducts [AC(PPh₃)₂]⁺ possess a π electron lone pair at carbon and they can easily be protonated to the dications [AC(H)(PPh₃)₂]²⁺. The calculations of the dications indicate that the molecules are best represented as complexes L→(CHA)²⁺←L (L=PPh₃) where a carbene dication is stabilized by the ligands. The central carbon atom in the cations and even in the dications carries a negative partial charge, which is larger than the negative charge at fluorine. There is also the peculiar situation in which the carbon–fluorine bonds in [FC(PPh₃)₂]⁺ and [FC(H)(PPh₃)₂]²⁺ exhibit the expected polarity with the negative end at fluorine, but the carbon atom has a larger negative charge than fluorine. Given the similarity of carbodiphosphorane C(PPh₃)₂ and carbodicarbene C(NHC)₂, we expect that analogous compounds [AC(NHC)₂]⁺ and [AC(H)(NHC)₂]²⁺ with similar features as [AC(PPh₃)₂]⁺ and [AC(H)(PPh₃)₂]²⁺ can be isolated.     

A Triatomic Silicon(0) Cluster Stabilized by a Cyclic Alkyl(amino) Carbene

Reduction of the neutral carbene tetrachlorosilane adduct (cAAC)SiCl₄ (cAAC=cyclic alkyl(amino) carbene :C(CMe₂)₂(CH₂)N(2,6‐iPr₂C₆H₃) with potassium graphite produces stable (cAAC)₃Si₃, a carbene‐stabilized triatomic silicon(0) molecule. The Si?Si bond lengths in (cAAC)₃Si₃ are 2.399(8), 2.369(8) and 2.398(8) Å, which are in the range of Si?Si single bonds. Each trigonal pyramidal silicon atom of the triangular molecule (cAAC)₃Si₃ possesses a lone pair of electrons. Its bonding, stability, and electron density distributions were studied by quantum chemical calculations.     

Hypercoordinated diorganoantimony(III) compounds of types [2-(Me2NCH2)C6H4]2SbL and [PhCH2N(CH2C6H4)2]SbL (L = Cl,ONO2, OSO2CF3). Synthesis,structure and catalytic behaviour in the Henry reaction

The compounds [2-(Me₂NCH₂)C₆H₄]₂SbL (L = ONO₂ ( 2 ), OSO₂CF₃ ( 3 )) and [PhCH₂N(CH₂C₆H₄)₂]SbL (L = ONO₂ ( 5 ), OSO₂CF₃ ( 6 )) were prepared by reacting [2-(Me₂NCH₂)C₆H₄]₂SbCl ( 1 ) and [PhCH₂N(CH₂C₆H₄)₂]SbCl ( 4 ), respectively, with the appropriate silver(I) salt in a 1:1 molar ratio. The new species 2 – 6 were structurally characterized in solution using multinuclear NMR and in the solid state using infrared spectroscopy. The solid-state structures for compounds 2 , 4 and 6, as well as for the hydrolysis ionic product [{2-(Me₂N⁺HCH₂)C₆H₄}{2-(Me₂NCH₂)C₆H₄}SbOH][CF₃SO₃]⁻ ( 3h ) were determined using single-crystal X-ray diffraction. Medium to strong intramolecular N→ Sb interactions were observed in all these four compounds, thus resulting in hypercoordinated organoantimony(III) species 14-Sb-6 in 2 and 10-Sb-4 in the cation of 3h and in 4 and 6 . Compounds 1 – 6 and the starting amines PhCH₂NMe₂ and PhCH₂N(CH₂C₆H₄Br-2)₂ were investigated as catalysts in the Henry (nitroaldol) addition of nitromethane to benzaldehyde. The activity of compounds 1 – 6 resulted as an effect of the cooperation of the positively charged antimony with the negatively charged nitrogen.     

Recent advances in polyhydroxyalkanoate production by mixed aerobic cultures: from the substrate to the final product

Numerous bacteria have been found to exhibit the capacity for intracellular polyhydroxyalkanoates (PHA) accumulation. Current methods for PHA production at the industrial scale are based on their synthesis from microbial isolates in either their wild form or by recombinant strains. High production costs are associated with these methods; thus, attempts have been made to develop more cost-effective processes. Reducing the cost of the carbon substrates (e.g., through feeding renewable wastes) and increasing the efficiency of production technologies (including both fermentation and downstream extraction and recovery) are two such examples of these attempts. PHA production processes based on mixed microbial cultures are being investigated as a possible technology to decrease production costs, since no sterilization is required and bacteria can adapt quite well to the complex substrates that may be present in waste material. PHA accumulation by mixed cultures has been found under various operational conditions and configurations at both bench-scale and full-scale production. The process known as "feast and famine" or as "aerobic dynamic feeding" seems to have a high potential for PHA production by mixed cultures. Enriched cultures submitted to a transient carbon supply can synthesize PHA at levels comparable to those of pure cultures. Indeed, the intracellular PHA content can reach around 70% of the cell dry weight, suggesting that this process could be competitive with pure culture PHA production when fully developed. Basic and applied research of the PHA production process by mixed cultures has been carried out in the past decade, focusing on areas such as microbial characterization, process configuration, reactor operational strategies, process modeling and control, and polymer characterization. This paper presents a review of the PHA production process with mixed cultures, encompassing the findings reported in the literature as well as our own experimental results in relation to each of these areas.     

Spike-adding and reset-induced canard cycles in adaptive integrate and fire models

Nonlinear Dynamics - This paper focuses on the study of a new type of a planar, circular restricted three-body problem with an attractive artificial electrostatic field (E-field) at collinear...