Recent advances in the activation of boron and silicon reagents for stereocontrolled allylation reactions

Despite the popularity of boron and silicon allylation reagents in stereocontrolled synthesis, they suffer from a number of inherent limitations that have slowed down their development as synthetic tools for nucleophilic additions to carbonyl compounds and imine derivatives. These limitations are the low reactivity and diastereoselectivity of allyl trialkylsilane reagents, and the lack of catalytic systems for the activation and substoichiometric control of enantioselectivity in the additions of allyl boron reagents. To develop more efficient and general methods for the control of absolute stereochemistry in the resulting homoallylic alcohols, new approaches aimed at solving the problem of activation of allylic boron and silicon reagents are needed. This Minireview describes a number of recent approaches that have been devised to address this problem.     

Three-dimensional Monte Carlo simulations of the dynamics of macromolecular particles in solutions flowing in mesopores

Numerical simulations are developed to calculate the dynamic equilibrium probability distribution functions (PDF) for macromolecular rod-like particles suspended in a fluid under hydrodynamic flow inside mesopores. The simulations take into account the effects of Brownian and hydrodynamic forces acting on the particles, as well as diffusive collisions of the particles with the solid surface boundaries. An algorithm is developed for this purpose based on Jeffery’s equations for the dynamics of ellipsoidal objects in bulk fluids, and on a mechanism of restitution for the diffusive collisions. The results are presented with a focus on the depletion layer next to two types of solid boundaries, ideally flat and rough. They demonstrate the significance of numerical simulations in 3D compared to previous results based on a 2D approach. In particular, we are able to obtain a complete topography for the PDFs segmented as a hierarchy in the depletion layer.     

Functionalized porous silica microspheres as scavengers in parallel synthesis

The use of solid scavengers in parallel solution-phase organic synthesis is an effective method for work-up and purification. Functionalized macroreticular or gel-form polystyrene particles are generally used for scavenging applications, how ever these materials have some limitations. We have developed new scavenging reagents based on ultrapure silica microspheres displaying a variety of functional groups useful for sequestering impurities from reaction products. These materials are easy to handle, have excellent mass-transfer properties, and are efficient scavengers in both polar and nonpolar organic solvents. The properties of these materials were tailored specifically to fit the needs of a medicinal chemist employing parallel synthesis techniques in current commercial equipment. Results are presented from head-to-head comparisons with conventional scavengers in tests designed to demonstrate the versatility of these new materials.     

High-load, hybrid Si-ROMP reagents

The combination of norbornenyl-tagged (Nb-tagged) silica particles and functionalized Nb-tagged monomers for the generation of hybrid Si-ROMP reagents and scavengers is reported. Specifically Si-ROMP-derived bis-acid chloride, dichlorotriazine, and triphenylphosphine scavenger/reagents have been grafted from the surface of silica particles utilizing surface-initiated, ring-opening metathesis polymerization (ROMP). These hybrid polymeric materials combine the physical properties of current immobilized silica reagents and represent a key advancement in load by merging the inherent tunable properties of the ROMP-derived oligomers with silica supports for application in a parallel synthesis.     

Simultaneous bioassays in a microfluidic channel on plugs of different magnetic particles

Magnetic particles coated with specific biomolecules are often used as solid supports for bioassays but conventional test tube based techniques are time consuming and labour intensive. An alternative is to work on magnetic particle plugs immobilised inside microfluidic channels. Most research so far has focussed on immobilising one type of particle to perform one type of assay. Here we demonstrate how several assays can be performed simultaneously by flushing a sample solution over several plugs of magnetic particles with different surface coatings. Within a microchannel, three plugs of magnetic particles were immobilised with external magnets. The particles featured surface coatings of glycine, streptavidin and protein A, respectively. Reagents were then flushed through the three plugs. Molecular binding occurred between matching antigens and antibodies in continuous flow and was detected by fluorescence. This first demonstration opens the door to a quicker and easier technique for simultaneous bioassays using magnetic particles.     

Le cyclone réacteur IV: Mesure de l'efficacité des transferts de chaleur entre les parois et les phases gazeuse et solide

The purpose of the present paper is the experimental study of different mechanisms of heat transfer for both gas and the solid phases inside a cyclone reactor. The measurements are based on the study of the outlet temperature of the gas and of the particles as a function of the inlet Reynolds number (385–11 000), of the wall temperature (630–1150 K), of the nature of the carrier gas (air, argon, CO₂, (helium) and of the particles (sand, bronze), and of the particle size (radius of particles from 0.1 to 0.5 × 10⁻³ m). It is shown that the particles are heated mainly during their contact with the heated wall and that the efficiency of the wall-particle and wall-carrier gas transfers decrease when the solid flow rate increases. Simple scale-up relationships are proposed to represent the extent of these two mechanisms as a function of operating conditions.     

Porous agglomerates in the general linear flow field

We calculate the flow within and around a porous spherical agglomerate suspended in the general linear flow field, and also the flow induced by its rotation. We use the Stokes equations exterior to the particle and the Brinkman equations inside it. The effect of particle permeability on the flow is expressed via the Brinkman parameter beta = r(0)/square root of k, where r0 is particle radius and k is its permeability. With translational creeping motion of porous spheres in a quiet fluid investigated by Debye and Bueche [P. Debye, A.M. Bueche, J. Chem. Phys. 16 (6) (1943) 573-579], this study provides information necessary for investigating dynamics of porous particles moving in creeping shear flows under the action of external forces and torques. The agglomerate flow field solutions are used to calculate the effective viscosity of a dilute suspension of porous solid aggregates, which generalizes the well-known Einstein's equation for solid suspensions. The agglomerate effective viscosity diameter is proposed which allows using the Einstein's formula evaluation of the agglomerates suspension viscosity.     

Enzymatically-generated fluorescent detection in micro-channels with internal magnetic mixing for the development of parallel microfluidic ELISA

The Enzyme-Linked Immuno-Sorbent Assay, or ELISA, is commonly utilized to quantify small concentrations of specific proteins for a large variety of purposes, ranging from medical diagnosis to environmental analysis and food safety. However, this technique requires large volumes of costly reagents and long incubation periods. The use of microfluidics permits one to specifically address these drawbacks by decreasing both the volume and the distance of diffusion inside the micro-channels. Existing microfluidic systems are limited by the necessary control of extremely low flow rates to provide sufficient time for the molecules to interact with each other by diffusion only. In this paper, we describe a new microfluidic design for the realization of parallel ELISA in stop-flow conditions. Magnetic beads were used both as a solid phase to support the formation of the reactive immune complex and to achieve a magnetic mixing inside the channels. In order to test the detection procedure, the formation of the immune complex was performed off-chip before the reactive beads were injected into the reaction chamber. Anti-streptavidin antibodies were quantified with low picomolar sensitivity (0.1-6.7 pM), a linear range of 2 orders of magnitude and good reproducibility. This work represents the first step toward a new platform for simple, highly effective and parallel microfluidic ELISA.     

Solid-phase UV spectroscopic multisensor for the simultaneous determination of caffeine, dimenhydrinate and acetaminophen by using partial least squares multicalibration

A straightforward flow-through multisensor was developed for the fast simultaneous determination of caffeine (CF), dimenhydrinate (DMH) and acetaminophen (AAP) based on the integration of their retention and UV detection. A diode array spectrophotometer was used to monitor the inherent UV full-spectra in the range 245-310 nm of the analytes retained on C(18) bonded phase beads packed in a flow cell, without requiring additional reagents or derivatization processes. The extensively overlapped spectra of the analytes retained on the solid support could be resolved by partial least squares (PLS) regression. After collecting the response of the multisensor, its active microzone was regenerated by using methanol as the eluting agent, leaving it ready for the next determination. The proposed multisensor has been satisfactorily applied for the analysis of synthetic and real samples with different nominal contents of these active principles.     

Molecularly imprinted polymer as a solid phase extractor in flow analysis

Molecularly imprinted polymers (MIPs) are novel alternative materials for solid phase extraction. Applications in flow analysis are recent and enhanced in-line separation/concentration procedures have been proposed. Use of flow systems is very important in the context. The aim of this review is then to highlight the implementation of MIP as solid phase extractor in flow analysis, emphasizing potentialities, limitations and applications.     

Continuous particle separation in a microchannel having asymmetrically arranged multiple branches

A new method for continuous size separation and collection of particles in microfabricated devices, asymmetric pinched flow fractionation (AsPFF), has been proposed and demonstrated. This method improves the separation scheme of pinched flow fractionation (PFF), which utilizes a laminar flow profile inside a microchannel. In this study, multiple branch channels with different channel dimensions were arranged at the end of the pinched segment, so that the flow rate distributions to each branch channel were varied, and a large part of the liquid was forced to go through one branch channel (drain channel). In the proposed channel system, the flow profile inside the microchannel was asymmetrically amplified, enabling the separation of one-order smaller particles compared with PFF. After introducing the method, we examined the effect of the asymmetric amplification by controlling the outlet of the drain channel. Also, a mixture of 1.0 approximately 5.0 microm particles was separated, and erythrocytes were successfully separated from blood. The results indicate that the AsPFF method could be applied to the separation of much smaller-size particles, since more precise separation can be achieved simply by changing the geometries of branch channels.     

Characterisation and analysis of micro-contaminants in industrial polymers

Analysis of very small particles can present problems. This paper describes the application of temperature programmed solid insertion probe mass spectrometry (TP-SIP-MS), scanning electron microscopy and SEM X-ray microanalysis to the identification of foreign particles present in an industrial product. The relative advantages and limitations of the techniques are discussed. It is shown that TP-SIP-MS is a powerful tool for such work and complements the use of more conventional microanalytical methods.     

炔酰胺类缩合剂研究进展

缩合剂是指用于促成羧酸与胺或者醇直接缩合构建酰胺键或酯键的一类试剂的总称.由于酰胺和酯的重要性,缩合剂的开发成为了学术界与工业界广泛关注的一个重要研究方向.多肽合成就是α-氨基酸在缩合剂的作用下反复形成酰胺键的过程,因此,缩合剂在多肽合成中发挥着至关重要的作用.当前多肽合成所使用的试剂和技术大多是20世纪50~80年代发展起来的,这些试剂和技术的天生弊端逐渐显现出来.比如传统多肽缩合剂过度活化α-氨基酸而诱发的外消旋化和其它副反应导致的副产物成为药物多肽生产过程中一个极为关切的问题.另外固相多肽合成的低原子经济性给可持续发展带来了极大的挑战.这些问题只能依靠原始创新的颠覆性技术和全新的缩合方法来解决.我们课题组致力于通过发展新试剂和新反应来解决多肽与蛋白质化学合成领域的难题.本文系统介绍了我们发展的一种结构全新的炔酰胺类缩合试剂及其在酰胺、酯、大环内酯、多肽、硫代多肽合成中的应用研究进展.     

金属有机骨架薄膜材料的三阶非线性光学性能研究进展

金属有机骨架(MOFs)材料因其可设计的结构以及灵活可控的配位模式,在三阶非线性光学(NLO)领域引起了广泛的关注。与液体分散状态相比,MOFs在固体状态下的三阶NLO性能更为重要,这不仅可以深入了解MOFs本身所固有的光学性能,还有助于实现MOFs在光学器件中的实际应用。然而,由于散射的存在和透光率的限制,单独的MOFs材料难以直接实现固体状态下的三阶NLO性能研究,将MOFs制备成具有较好光学透过性的薄膜是研究其NLO性能最为可行的一种策略。MOFs薄膜不仅很好地继承了MOFs所固有的三阶NLO性能,而且还结合了薄膜的高透光率以及灵活的机械性能。基于此,本文分析总结了MOFs薄膜的制备方法及其NLO性能研究方面的相关工作,并根据目前MOFs薄膜在三阶NLO性能方面的研究现状对其未来发展予以了展望。     

金属有机骨架薄膜材料的三阶非线性光学性能研究进展

金属有机骨架(MOFs)材料因其可设计的结构以及灵活可控的配位模式,在三阶非线性光学(NLO)领域引起了广泛的关注。与液体分散状态相比,MOFs在固体状态下的三阶NLO性能更为重要,这不仅可以深入了解MOFs本身所固有的光学性能,还有助于实现MOFs在光学器件中的实际应用。然而,由于散射的存在和透光率的限制,单独的MOFs材料难以直接实现固体状态下的三阶NLO性能研究,将MOFs制备成具有较好光学透过性的薄膜是研究其NLO性能最为可行的一种策略。MOFs薄膜不仅很好地继承了MOFs所固有的三阶NLO性能,而且还结合了薄膜的高透光率以及灵活的机械性能。基于此,本文分析总结了MOFs薄膜的制备方法及其NLO性能研究方面的相关工作,并根据目前MOFs薄膜在三阶NLO性能方面的研究现状对其未来发展予以了展望。     

锂离子电池介观尺度光滑粒子水力学模型

针对锂离子电池内耦合电化学反应的多物理传输过程,采用光滑粒子水力学数值技术,开发了可以考虑电极(包括隔膜)介观微结构的数值模型.以电极中固体活性物颗粒尺寸为主要考虑参数,初步探讨了该模型用于电极介观微结构设计的可行性.模型模拟得到放电过程中电池内部Li/Li+浓度场、固/液相电势场以及交换流密度等微观细节分布,以及电池宏观性能如输出电压等,据此可以分析并揭示电池放电过程的基础物理化学机制、电池宏观性能与构成电极的固体活性物颗粒尺寸之间的关联.研究还发现:当阴、阳极固体活性物颗粒尺寸均较小时,固体活性物颗粒内部Li分布更为均匀,电化学反应更均匀发生,电池输出电压最高.     

Continuous flow in open microfluidics using controlled evaporation

This paper presents a method for programming the flow rate of liquids inside open microfluidic networks (MFNs). A MFN comprises a number of independent flow paths, each of which starts with an open filling port, has a sealed microchannel in which assays can be performed, and an open capillary pump (CP). The MFN is placed over Peltier elements and its flow paths initially fill owing to capillary forces when liquids are added to the filling ports. A cooling Peltier element underneath the filling ports dynamically prevents evaporation in all filling ports using the ambient temperature and relative humidity as inputs. Another Peltier element underneath the CPs heats the pumps thereby inducing evaporation in the CPs and setting the flow rate in the microchannels. This method achieves flow rates in the microchannels ranging from approximately 1.2 nL s(-1) to approximately 30 pL s(-1), and is able to keep 90% of a 0.6 microL solution placed in an open filling port for 60 min. This simple and efficient method should be applicable to numerous assays or chemical reactions that require small and precise flow of liquids and reagents inside microfluidics.     

Genetically encoded tetrazine amino acid directs rapid site-specific in vivo bioorthogonal ligation with trans-cyclooctenes

Bioorthogonal ligation methods with improved reaction rates and less obtrusive components are needed for site-specifically labeling proteins without catalysts. Currently no general method exists for in vivo site-specific labeling of proteins that combines fast reaction rate with stable, nontoxic, and chemoselective reagents. To overcome these limitations, we have developed a tetrazine-containing amino acid, 1, that is stable inside living cells. We have site-specifically genetically encoded this unique amino acid in response to an amber codon allowing a single 1 to be placed at any location in a protein. We have demonstrated that protein containing 1 can be ligated to a conformationally strained trans-cyclooctene in vitro and in vivo with reaction rates significantly faster than most commonly used labeling methods.