The MARTINI force field: coarse grained model for biomolecular simulations

We present an improved and extended version of our coarse grained lipid model. The new version, coined the MARTINI force field, is parametrized in a systematic way, based on the reproduction of partitioning free energies between polar and apolar phases of a large number of chemical compounds. To reproduce the free energies of these chemical building blocks, the number of possible interaction levels of the coarse-grained sites has increased compared to those of the previous model. Application of the new model to lipid bilayers shows an improved behavior in terms of the stress profile across the bilayer and the tendency to form pores. An extension of the force field now also allows the simulation of planar (ring) compounds, including sterols. Application to a bilayer/cholesterol system at various concentrations shows the typical cholesterol condensation effect similar to that observed in all atom representations.     

Mechanism of the copper-free palladium-catalyzed Sonagashira reactions: multiple role of amines

Amines used as bases in copper-free, palladium-catalyzed Sonogashira reactions play a multiple role. The oxidative addition of iodobenzene with [Pd(0)(PPh(3))(4)] is faster when performed in the presence of amines (piperidine>morpholine). Amines also substitute one ligand L in trans-[PdI(Ph)(L)(2)] (L=PPh(3), AsPh(3)) formed in the oxidative addition. This reversible reaction, which gives [PdI(Ph)L(R(2)NH)], is favored in the order AsPh(3)>PPh(3) and piperidine>morpholine. Two mechanisms are proposed for Sonogashira reactions, depending on the ligand and the amine. When L=PPh(3), its substitution by the amine in trans-[PdI(Ph)(PPh(3))(2)] is less favored than that of the alkyne. A mechanism involving prior coordination of the alkyne is suggested, followed by deprotonation of the ligated alkyne by the amine. When L=AsPh(3), its substitution in trans-[PdI(Ph)(AsPh(3))(2)] by the piperidine is easier than that by the alkyne, leading to a different mechanism: substitution of AsPh(3) by the amine is followed by substitution of the second AsPh(3) by the alkyne to generate [PdI(Ph)(amine)(alkyne)]. Deprotonation of the ligated alkyne by an external amine leads to the coupling product. This explains why the catalytic reactions are less efficient with AsPh(3) than with PPh(3) as ligand.     

Progress toward a rationally designed, chemically powered rotary molecular motor

Building on prototype 1, which achieves 120 degrees of phosgene-powered unidirectional rotation to rotamer 6 (see Figure 5 in the full article), 7 was designed to accomplish repeated unidirectional rotation (see Scheme 7). Compound 7 contains an amino group on each blade of the triptycene and a 4-(dimethylamino)pyridine (DMAP) unit to selectively deliver phosgene (or its equivalent) to the amine in the "firing position". The synthesis of 7 is described: the key constructive steps are a benzyne addition to an anthracene to generate the triptycene, a stilbene photocyclization to construct the helicene, and a Stille coupling to incorporate the DMAP unit. The DMAP unit was shown to regioselectively relay 1,1'-carbonyldiimidazole (but not phosgene) to the proximal amino group, as designed, but rotation of the triptycene does not occur. Extensive attempts to troubleshoot the problem led to the conclusion that the requisite intramolecular urethane formation, as demonstrated in the prototype (1 --> 4), does not occur with 7 (to give 85) or 97 (to give 100). We speculate that either (i) hydrogen bonding between the hydroxypropyl group and functionality present in 7 but absent from 1 or (ii) a Bürgi-Dunitz (or similar) interaction involving the DMAP (see 106) prevents achievement of a conformation conducive to intramolecular urethane formation.     

Interaction between quercetin-copper(II) complex and DNA with the use of the Neutral Red dye fluorophor probe

The interaction of quercetin-Cu(II) complex with calf thymus DNA was investigated with the use of Neutral Red (NR) dye as a spectral probe by the application of UV-vis spectrophotometry, cyclic voltammetry and synchronous fluorescence spectroscopy. The results showed that both quercetin-Cu(II) complex and the NR molecule can intercalate into the double helix of the DNA. The 2:1 quercetin:Cu(II) complex (estimated binding constant = 2.85 × 10⁹) is stabilized by intercalation in the DNA (binding constant, K_{[quercetin-Cu(II)-DNA]} = (1.82 ± 0.20) × 10⁵ M⁻¹), and displaces the NR dye from the NR-DNA complex in a competitive reaction. Cyclic voltammetry studies confirm the intercalation reaction and show that the ratio (K_R/K_O) of binding constants for the reduced and oxidized forms of the metal complex is 2.05. Furthermore, the alternative least squares (ALS) method was applied to resolve a complex two-way array of the absorption spectra data. This yielded the equilibrium concentration profiles of each component in the reaction (NR, NR-DNA and quercetin-Cu(II)) as well as the corresponding pure spectra. The extracted profiles showed that at equilibrium the [NR-DNA] and [NR] trends decreased and increased symmetrically, respectively, with approximately linear behaviour being observed below 10 × 10⁻⁶ mol L⁻¹ of the added quercetin-Cu²⁺ complex. Thereafter, these trends converged asymptotically. The free [quercetin-Cu(II)] trend-line at equilibrium was linear over the whole range of the complex added. It was possible to estimate the approximate value of the equilibrium constant of the exchange process (approximately 5 × 10⁻¹) involving the intercalation of the quercetin-Cu(II) complex. It was also found that about 35% of the bound complex was unaccounted by the intercalation reaction, presumably being stabilized at an alternative site.     

Magnetic properties and magnetic structures of Cu3(OD)4XO4, X=Se or S: cycloidal versus collinear antiferromagnetic structure

We report a comparative study of the magnetic properties of synthetic Cu3(OH)4(SO4)x(SeO4)1-x and the magnetic structures of the parent compounds. All compounds are isostructural and belong to the orthorhombic class of parent compounds. They consist of 3-legged ribbons of edge-sharing copper octahedra connected by micro3-OH and XO4 (X=S or Se). XO4 acts both as one-atom and three-atom bridges to connect seven Cu atoms (six Cu(2) and one Cu(1)) belonging to three neighboring ribbons. The two end members behave as low-dimensional AF with a long-range antiferromagnetic state below 5 (X=S) and 8 K (X=Se); the former shows evidence of a canting. Analyses of the neutron powder diffraction data for X=S were shown to display an ordered magnetic state (k=0 0 0) where the moments of Cu(2) within the two outer legs are collinear and parallel within each leg but antiparallel from each other; the orientation of the moments of Cu(2) is the c axis. In contrast, for X=Se k=approximately 1/7 0 0 and the magnetic structure is cycloidal and transforms progressively from being incommensurate (T>3 K) to commensurate (T相似文献   

Diastereoselective alkynylation of N-p-tolylsulfinylimines with aluminum acetylides

The addition of alkynyl dimethyl aluminum compounds onto N-p-tolylsulfinylimines was investigated. The reaction was proved to be totally regioselective, leading to propargylamines with high diastereoselectivity (up to 99% de). Addition of aluminum derivatives gave a reversal of diastereoselectivity compared to the addition reaction of lithium acetylide.     

A novel microfluidic flow-injection analysis device with fluorescence detection for cation sensing. Application to potassium

A microfabricated device has been developed for fluorimetric detection of potassium ions without previous separation. It is based on use of a fluorescent molecular sensor, calix–bodipy, specially designed to be sensitive to and selective for the target ion. The device is essentially made of a Y-shape microchannel moulded in PDMS fixed on a glass substrate. A passive mixer is used for mixing the reactant and the analyte. The optical detection arrangement uses two optical fibres, one for excitation by a light-emitting diode, the other for collection of the fluorescence. This system enabled the flow-injection analysis of the concentration of potassium ions in aqueous solutions with a detection limit of 0.5 mmol L⁻¹ and without interference with sodium ions. A calibration plot was constructed using potassium standard solutions in the range 0–16 mmol L⁻¹, and was used for the determination of the potassium content of a pharmaceutical pill. Figure Photography of the microfluidic channel showing the ridges in the PDMS substrate at the top of the channel     

Quantitative and morphological analysis of biofilm formation on self-assembled monolayers

In spite of intensive studies over the past two decades, the influence of surface properties on bacterial adhesion and biofilm formation remains unclear, particularly on late steps. In order to contribute to the elucidation of this point, we compared the impact of two different substrates on the formation of bacterial biofilm, by analysing bacterial amount and biofilm structure on hydrophilic and hydrophobic surfaces. The surfaces were constituted by NH₂- and CH₃-terminated self-assembled monolayers (SAMs) on silicon wafers, allowing to consider only the surface chemistry influence because wafers low roughness. A strain of Escherichia coli K12, able to produce biofilm on abiotic surfaces, was grown with culture durations varying from 4 h to 336 h on both types of substrates. The amount of adhered bacteria was determined after detachment by both photometry at 630 nm and direct counting under light microscope, while the spatial distribution of adhered bacteria was observed by fluorescence microscopy. A general view of our results suggests a little influence of the surface chemistry on adherent bacteria amount, but a clear impact on dynamics of biofilm growth as well as on biofilm structure. This work points out how surface chemistry of substrates can influence the bacterial adhesion and the biofilm formation.