Microfluidic platform for combinatorial synthesis in picolitre droplets

This paper presents a droplet-based microfluidic platform for miniaturized combinatorial synthesis. As a proof of concept, a library of small molecules for early stage drug screening was produced. We present an efficient strategy for producing a 7 × 3 library of potential thrombin inhibitors that can be utilized for other combinatorial synthesis applications. Picolitre droplets containing the first type of reagent (reagents A(1), A(2), …, A(m)) were formed individually in identical microfluidic chips and then stored off chip with the aid of stabilizing surfactants. These droplets were then mixed to form a library of droplets containing reagents A(1-m), each individually compartmentalized, which was reinjected into a second microfluidic chip and combinatorially fused with picolitre droplets containing the second reagent (reagents B(1), B(2), …, B(n)) that were formed on chip. The concept was demonstrated with a three-component Ugi-type reaction involving an amine (reagents A(1-3)), an aldehyde (reagents B(1-7)), and an isocyanide (held constant), to synthesize a library of small molecules with potential thrombin inhibitory activity. Our technique produced 10(6) droplets of each reaction at a rate of 2.3 kHz. Each droplet had a reaction volume of 3.1 pL, at least six orders of magnitude lower than conventional techniques. The droplets can then be divided into aliquots for different downstream screening applications. In addition to medicinal chemistry applications, this combinatorial droplet-based approach holds great potential for other applications that involve sampling large areas of chemical parameter space with minimal reagent consumption; such an approach could be beneficial when optimizing reaction conditions or performing combinatorial reactions aimed at producing novel materials.     

New supramolecular interactions for electrochemical sensors development: different cucurbit[8]uril sensing platform designs

Three different strategies for cucurbit[8]uril immobilization on a glassy carbon electrode have been assayed. The electrochemical properties of the resulting modified electrodes in solutions containing neutral, positively and negatively charged potential cucurbit[8]uril guests were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The comparison of the electrochemical behaviour exhibited by the unmodified electrodes against various probes, with respect to that of each modified electrode, resulted in an appropriate method to choose among different strategies for the development of electrochemical sensors. These sensors are based on the incorporation of the cucurbit[8]uril molecular selection properties that depend on the chemical characteristics of the potential analytes. Furthermore, atomic force microscopy was employed for the characterization of the different surfaces developed.     

First report on the kinetics of the uncatalyzed esterification of cellulose under homogeneous reaction conditions: a rationale for the effect of carboxylic acid anhydride chain-length on the degree of biopolymer substitution

The kinetics of the homogeneous acylation of microcrystalline cellulose, MCC, with carboxylic acid anhydrides with different acyl chain-length (Nc; ethanoic to hexanoic) in LiCl/N,N-dimethylacetamide have been studied by conductivity measurements from 65 to 85 °C. We have employed cyclohexylmethanol, CHM, and trans-1,2-cyclohexanediol, CHD, as model compounds for the hydroxyl groups of the anhydroglucose unit of cellulose. The ratios of rate constants of acylation of primary (CHM; Prim-OH) and secondary (CHD; Sec-OH) groups have been employed, after correction, in order to split the overall rate constants of the reaction of MCC into contributions from the discrete OH groups. For the model compounds, we have found that k_(Prim-OH)/k_(Sec-OH) > 1, akin to reactions of cellulose under heterogeneous conditions; this ratio increases as a function of increasing Nc. The overall, and partial rate constants of the acylation of MCC decrease from ethanoic- to butanoic-anhydride and then increase for pentanoic- and hexanoic anhydride, due to subtle changes in- and compensations of the enthalpy and entropy of activation.     

Traceless chemical ligations from O-acyl serine sites

Chemical ligation via O- to N-acyl transfer of O-acylated serine containing peptides affords serine containing native peptides via 8- and 11-membered cyclic transition states opening the door to a wide variety of potential applications to peptide elaboration. The feasibility of these traceless chemical ligations is feasible as supported by computation.     

Effect of shape and interstice on surface enhanced Raman scattering (SERS) of molecules adsorbed on gold nanoparticles in the near‐dipole and quadrupole regions

Surface enhanced Raman scattering (SERS) of adsorbed molecule on colloidal gold nanoparticles of different shapes, namely nanospheres (NSs), nanorods (NRs), and nanoprisms (NPs) as well as the three NPs arrays of different interstice prepared by NS lithography, are studied with incident wavenumbers in the near‐dipole and near‐quadrpole regions of the nanoparticles. In the colloidal gold nanoparticles, the SERS enhancement is the largest for the sharp tip followed by the truncated tip NPs, then the NRs and least enhancement for the NSs. This decreasing order of enhancement occurs although the incident wavenumber was near the dipole resonance of NSs and the quadrupole resonance for the NPs. These varied enhancements are explained in part as due to the binding energies of the nanocrystal facets, but the larger contribution results from the plasmon electromagnetic fields. A parallel finite difference time domain (FDTD) calculations were carried out, which corporate the experimental results and show agreement with ratios of the SERS enhancement for the different shapes. The normalized SERS intensity for NPs of different interstice distances show a sharp rise with the decrease of the interstice distances because of interparticle dipolar and quadrupolar coupling as evidenced also by FDTD calculations. Furthermore, these calculations show that the enhancement is polarization independent for an incident wavelength near quadrupole resonance but polarization dependent for an incident wavelength near the plasmon dipole transition. In the last case, the enhancement is larger by an order of magnitude for a polarization parallel to the NPs bisector than for polarization normal to the bisector with no hot spots for the relatively large interstice dimensions used. Copyright © 2012 John Wiley & Sons, Ltd.     

Some remarks on the geometry of superspace supergravity

In this note, we first give a quick presentation of the supergeometry underlying supergravity theories, using an intrinsic differential geometric language. For this, we adopt the point of view of Cartan geometries, and rely as well on the work of John Lott, who has found a unified geometrical interpretation of the torsion constraints for many supergravity theories, based on the use of H-structures. In this framework, the constraints amount to requiring first-order integrability of H-structures, for a specific supergroup H.The supergroup H used by Lott is not the usual diagonal representation of the Lorentz group on superspace, but an extension of the latter. This extension appears to be natural and it can be related to the super-Poincaré group. We also observe that the constraints arising from the requirement of first-order integrability have basically the same form, in any spacetime dimension.Looking at supergravity from an affine viewpoint (i.e. as a gauge theory for the super-Poincaré group), we show that requiring first-order integrability amounts to requiring the equivalence, up to gauge transformations, between infinitesimal gauge supertranslations acting on the supervielbein and infinitesimal superdiffeomorphisms acting on the supervielbein.The latter action is performed through a covariant Lie derivative, whose expression involves naturally the supertorsion tensor. We use this expression to show that the term added to the spin connection, in the supercovariant derivative of d=11 supergravity, has a natural superspace origin. In particular, the 4-form field strength is related to a specific component of the supertorsion tensor.We conclude by some general remarks concerning Killing spinors in geometry and supergravity, discussing their possible interpretations, as Killing vector fields on a specific supermanifold on one hand, and as parallel spinors for an appropriate connection on the other hand. We show that this last interpretation is very natural from the point of view of Klein and Cartan geometries.     

Sol–gel synthesis of 8 nm magnetite (Fe3O4) nanoparticles and their magnetic properties

Magnetite (Fe₃O₄) nanoparticles were successfully synthesized by a sol–gel method. The obtained nanoparticles were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy dispersive analysis by X-ray (EDAX), transmission electron microscopy (TEM), superconducting quantum interference device (SQUID) and Mössbauer spectrometry. XRD and Mössbauer measurements indicate that the obtained nanoparticles are single phase. TEM analysis shows the presence of spherical nanoparticles with homogeneous size distribution of about 8 nm. Room temperature ferromagnetics behavior was confirmed by SQUID measurements. The mechanism of nanoparticles formation and the comparison with recent results are discussed. Finally, the synthesized nanoparticles present a potential candidate for hyperthermia application given their saturation magnetization.     

Effects of substrate-induced-strain on the structural and transport properties of La0.7Ca0.3MnO3 thin films

We have studied the structural and electrical properties of epitaxial La_0.7Ca_0.3MnO₃ (LCMO) thin films prepared by metal organic deposition under different types and degrees of substrate-induced strain. 40-nm-thick films have been epitaxially grown on single-crystalline (LaAlO₃)_0.3?C(SrAlTaO₆)_0.7 (negligible tensile strain), SrTiO₃ (tensile strain) and LaAlO₃ (compressive strain) substrates. High-resolution X-ray diffraction and reciprocal space maps demonstrate a direct correlation between the crystalline quality and the substrate-induced strain. The electrical properties were found to be strongly dependent on the substrate used. The temperature dependence of resistivity curves was fitted using various approaches in different phases (below and above the ferromagnetic transition temperature T _P). In the ferromagnetic metallic phase, ??(T) follows a T ^?? power law. The obtained values of the coefficient ???(3.5?C4) indicate that the electrical transport in our films is a combination of spin wave scattering processes and electron?Cmagnon or two-magnon scattering phenomena. In the paramagnetic insulator phase, the activation energy E _A and the variable range hopping characteristics (characteristic temperature T ₀) were found to be strongly dependent on the strain-induced lattice mismatch between the LCMO and the substrate used.     

Variational problem in the non-negative orthant of ℝ<Superscript>3</Superscript>: reflective faces and boundary influence cones

In this paper we consider the variational problem in the non-negative orthant of ℝ³. The solution of this problem gives the large deviation rate function for the stationary distribution of an SRBM (Semimartingal Reflecting Brownian Motion). Avram, Dai and Hasenbein (Queueing Syst. 37, 259–289, 2001) provided an explicit solution of this problem in the non-negative quadrant. Building on this work, we characterize reflective faces of the non-negative orthant of ℝ ^d , we construct boundary influence cones and we provide an explicit solution of several constrained variational problems in ℝ³. Moreover, we give conditions under which certain spiraling paths to a point on an axis have a cost which is strictly less than the cost of every direct path and path with two pieces.     

Predicting initial erosion during the hole erosion test by using turbulent flow CFD simulation

CFD simulation with enhanced modeling of turbulence and near-wall treatment is used to model water–clay mixtures flowing through a cylindrical pipe domain. Effects on the wall-shear stress resulting from varying water clay content and applied hydraulic gradient are analyzed. Various parametric studies were performed and had shown that the two-dimensional modelling introduced in the present study does not yield a uniform wall-shear stress along the pipe wall and that clay concentration affects significantly the wall-shear stress value. This is in contrast with the common hypothesis used in one-dimensional modeling approaches where this stress is assumed constant and which gives rise to uniform erosion along the pipe wall. The obtained results had enabled predicting more realistically erosion amount and had allowed for understanding the irregular eroded hole wall shape as observed experimentally after performing the standard hole erosion test.