Multidimensional view of amyloid fibril nucleation in atomistic detail

Starting from a disordered aggregate, we have simulated the formation of ordered amyloid-like beta structures in a system formed by 18 polyvaline chains in explicit solvent, employing molecular dynamics accelerated by bias-exchange metadynamics. We exploited 8 different collective variables to compute the free energy of hundreds of putative aggregate structures, with variable content of parallel and antiparallel β-sheets and different packing among the sheets. This allowed characterizing in detail a possible nucleation pathway for the formation of amyloid fibrils: first the system forms a relatively large ordered nucleus of antiparallel β-sheets, and then a few parallel sheets start appearing. The relevant nucleation process culminates at this point: when a sufficient number of parallel sheets is formed, the free energy starts to decrease toward a new minimum in which this structure is predominant. The complex nucleation pathway we found cannot be described within classical nucleation theory, namely employing a unique simple reaction coordinate like the total content of β-sheets.     

A facile method for the synthesis of novel imidoyl iminosulfuranes from imidoyl azides

A novel and environmentally friendly method for the one-pot preparation of new imidoyl iminosulfuranes in high yield under microwave (MW) and solvent-free conditions from the corresponding imidoyl azides is presented. This efficient synthetic approach benefits from non-toxic and non-explosive precursors for the synthesis of imidoyl iminosulfuranes.     

On the on-line maintenance scheduling problem

A machine instantly serves requests but needs to undergo maintenance after serving a maximum of L requests. We want to maximize the number of requests served. In the on-line version, we prove that serving L requests before placing a maintenance is 0.5-competitive and is best possible for deterministic algorithms. We describe a 0.585-competitive randomized algorithm and show an upper bound of \(2L/(3L-1)\). We also analyze the empirical performance of various on-line algorithms on specific arrival distributions.     

Layered double hydroxides (LDHs): As efficient heterogeneous catalyst for the cyanosilylation of aromatic aldehydes

We report the first application of Layered Double Hydroxides (LDHs) as efficient and novel heterogeneous catalyst for the cyanosilylation of aldehydes with excellent yields and simple work up. The reaction between different aldehydes with electron-withdrawing and releasing groups and trimethylsilyl cyanide (TMSCN) proceeds in dry CH₂Cl₂ at room temperature in the presence of Mg-Al-Cu LDH. The catalyst recycled and reused for four times without loss of catalytic activity. The structures of all compounds were corroborated spectroscopically (¹H- and ¹³C-NMR, and elemental analysis). A plausible mechanism for this type of reaction is proposed.     

Synthesis of (E)-2-amino-N′-benzylidenehexahydroquinoline-3-carbohydrazide

Molecular Diversity - A one-pot, multi-component protocol for the synthesis of a new class of functionalized quinoline carbohydrazide derivatives via reaction of various anilines, dimedone,...     

Characterization of peptide immobilization on an acetylene terminated surface via click chemistry

Peptide (A-A-A-A-G-G-G-E-R-G-D)¹ conjugated surfaces were prepared on silicon surfaces through click chemistry. The amino acid sequence RGD is the cellular attachment site of a large number of extracellular matrices such as blood and cell surface proteins. Recent research has focused on developing RGD peptides which mimic cell adhesion proteins and integrins [1], [2].The steps involved the formation of an alkyne-terminated monolayer on Si(111), followed by linking the peptide to 4-azidophenyl isothiocyanate via a specific and gentle reaction. This was followed by the attachment of the azido peptide to the surface-bound alkynes using the Cu (I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The surface structures of the alkyne terminated monolayer and the attached peptide were characterized using high resolution impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared (ATR-FTIR) Spectroscopy. EIS characterization revealed the alkyne layer and the hydrophobic and polar regions of the attached peptide. XPS analysis showed a high surface coverage of the peptide on the silicon substrates and this was confirmed by FTIR.Our results confirmed a specific covalent attachment of the peptide on the silicon surfaces. This approach offers a versatile, experimentally simple, method for the specific attachment of peptide ligands. This approach would have applications for cell attachment and biosensors.