Biopolymer microparticle and nanoparticle formation within a microfluidic device

This paper reports a novel microfluidic method for the production of cross-linked alginate microparticles and nanoparticles. We describe a continuous process relying on both thermodynamic and hydrodynamic factors to form microdroplets. A rapid cross-linking reaction thereafter allows solidification of the polymer droplets either within the microfluidic device or "off-chip" to form alginate micro- and nanoparticles. Monodisperse droplets are generated by extruding an aqueous alginate solution using an axisymmetric flow-focusing design. As they flow downstream in the channel, due to water and the continuous phase being partially miscible, the water diffuses very slowly out of the polymeric droplets into the transport fluid, which causes the shrinkage of the drops and the condensation of the polymer phase. The resulting size of the solid particles depends on the polymer concentration and the ensuing balance between the kinetics of the cross-linking reaction and the volume loss due to solvent diffusion. This work details both a single-step microfluidic technique for the formation of alginate microparticles of sizes ranging from 1 to 50 microm via near-equilibrium solvent diffusion within a microfluidic device and thereafter a two-step method, which was shown to generate biopolymer nanoparticles of sizes ranging from 10 to 300 nm. These novel methodologies are extremely flexible and can be extended to the preparation of micro- and nanoparticles from a wide range of single or mixed synthetic and biologically derived polymers.     

Investigations into arylquinone atropisomers: synthesis and evaluation

An arylquinone capable of existing as two diastereromeric atropisomers was synthesized starting from dibenzofuran. Arylquinone 12 exists as a set of slowly interchanging diastereomeric atropisomers and arylquinone 4 exists as rapidly interchanging atropisomers.     

Investigations into a biomimetic approach toward CP-225,917 and CP-263,114

A biosynthesis of the structurally complex nonadride CP-225,917 (1) is outlined. A key step in this proposal is the dimerization of a C(16) anhydride derived from the condensation of lauric acid and oxaloacetic acid. An important element of this step is a templating effect imposed by two thioester linkages, reminiscent of a polyketide or fatty acid synthase pathway. On the basis of this principle, the dimerization of two C(11) anhydrides, templated by a 1,n-diol tether, leading to the core structure of CP-225,917 and CP-263,114 was investigated.     

Investigations into the synthesis of amine-linked neodisaccharides

Six tail-to-tail amine-linked neodisaccharides were synthesised as potential glycomimetics. Primary-primary linked compounds were synthesised using Mitsunobu chemistry with glucose-6-sulfonamides as nucleophiles and primary carbohydrate alcohols as electrophiles. Primary-secondary linked compounds were synthesised by epoxide ring opening with carbohydrate 6-amines. Deprotection of all neodisaccharides was carried out using dissolving metal reduction.     

Three-body collisions as a particle formation mechanism in silver nanoparticle synthesis

Silver nanoparticles were prepared in a tubular flow reactor using an evaporation-condensation technique. The size distribution of the particles was measured using standard aerosol instruments and electron microscopy. A comparison with results obtained by a discrete population balance model with molecule-by-molecule resolution suggest that the particles probably nucleate kinetically through a dimerization process instead of a thermodynamic pathway over a free energy barrier, as is typically described by classical nucleation theory. Furthermore, the kinetic rate of dimerization seems to be accompanied by a correction term, associated with the requirement of energy and momentum conservation in molecule-molecule collisions. This energy conservation requires the presence of three-body collisions at the very initial step of particle formation.     

Convenient formation of nanoparticle aggregates on microfluidic chips for highly sensitive SERS detection of biomolecules

Microfluidic chips combined with surface-enhanced Raman spectroscopy (SERS) offer an outstanding platform for rapid and high-sensitivity chemical analysis. However, it is nontrivial to conveniently form nanoparticle aggregrates (as SERS-active spots for SERS detection) in microchannels in a well-controlled manner. Here, we present a rapid, highly sensitive and label-free analytical technique for determining bovine serum albumin (BSA) on a poly(dimethylsiloxane) (PDMS) microfluidic chip using SERS. A modified PDMS pneumatic valve and nanopost arrays at the bottom of the fluidic microchannel are used for reversibly trapping gold nanoparticles to form gold aggregates, creating SERS-active spots for Raman detection. We fabricated a chip that consisted of a T-shaped fluidic channel and two modified pneumatic valves, which was suitable for fast loading of samples. Quantitative analysis of BSA is demonstrated with the measured peak intensity at 1,615 cm⁻¹ in the surface-enhanced Raman spectra. With our microfluidic chip, the detection limit of Raman can reach as low as the picomolar level, comparable to that of normal mass spectrometry.     

Studies toward the synthesis of spirolide C: exploration into the formation of the 23-membered all-carbon macrocyclic framework

The synthesis of two complex subunits en route to spirolide C is described. A key alkyllithium addition to an aldehyde joins the fragments, which are advanced in order to investigate a ring-closing metathesis to form the 23-membered all-carbon macrocyclic framework.     

Progress toward the total synthesis of saudin: development of a tandem Stille-oxa-electrocyclization reaction

[reaction: see text] A diastereoselective tandem Stille-oxa-electrocyclization reaction provides access to the core of the diterpenoid natural product saudin. Additionally, this new reaction sequence was extended to the convergent preparation of related polycyclic pyran systems.     

Spatially-resolved analysis of nanoparticle nucleation and growth in a microfluidic reactor

Microfluidic systems provide a unique platform for investigation of fundamental reaction processes, which is critical to understanding how to control nanostructure synthesis on a production scale. We have examined the synthesis of cysteine-capped CdS quantum dot nanocrystals (CdS-Cys) between two interdiffusing reagent streams in a continuous-flow microfluidic reactor. Using spatially resolved photoluminescence imaging and spectroscopy of the microreactor, we have acquired kinetic and mechanistic data on the CdS-Cys nanoparticle nucleation and growth, and observed a binary shift in the particle emission spectrum from a higher (2.9 eV) to lower (2.5 eV) energy emission peak within the first second of residence time. Several reactor models have been tested against the spatially and spectrally resolved signals, which suggest that homogeneous reaction and particle nucleation are diffusion-limited and occur only at the boundary between the two laminar streams, while a slower activation process occurs on a longer (seconds) time scale. The results provide direct insight into the rapid processes that occur during crystallization in microfluidic mixing channels, and demonstrate the potential of using controlled microfluidic environments with spatially resolved monitoring to conduct fundamental studies of nanocrystal nucleation and growth.     

Alternating droplet generation and controlled dynamic droplet fusion in microfluidic device for CdS nanoparticle synthesis

A multifunctional and high-efficiency microfluidic device for droplet generation and fusion is presented. Through unique design of the micro-channels, the device is able to alternately generate droplets, generating droplet ratios ranging from 1 ratio 5 to 5 ratio 1, and fuse droplets, enabling precise chemical reactions in several picoliters on a single chip. The controlled fusion is managed by passive control based on the channel geometry and liquid phase flow. The synthesis of CdS nanoparticles utilizing each fused droplet as a microreactor for rapid and efficient mixing of reagents is demonstrated in this paper. Following alternating droplet generation, the channel geometry allows the exclusive fusion of alternate droplets with concomitant rapid mixing and produces supersaturated solution of Cd2+ and S2- ions to form CdS nanoparticles in each fused droplet. The spectroscopic properties of the CdS nanoparticles produced by this method are compared with CdS prepared by bulk mixing.     

A simple microfluidic probe of nanoparticle suspension stability

We describe a simple experimental tool that enables stability of multicomponent nanoparticle suspensions to be readily assessed by establishing a confinement-imposed chemical discontinuity at the interface between co-flowing laminar streams in a microchannel. When applied to examine Al(2)O(3) nanoparticle suspensions, this method readily reveals compositions that are susceptible to aggregation even when conventional bulk measurements (zeta potential, dynamic light scattering, bulk viscosity) suggest only subtle differences between formulations. This microfluidic stability test enables simple and rapid assessment of quality and variability in complex multicomponent mixtures for which few, if any, comparable data exist. The paradoxical ease at which localized aggregation can be triggered in suspensions that would otherwise appear stable also serves as a caution to researchers undertaking tracer-based studies of nanomaterial suspensions.     

Performing the synthesis of a complex molecule on sequentially linked columns: toward the development of a "synthesis machine"

[reaction: see text] We describe the diastereoselective synthesis of a pharmaceutically active drug candidate via a column-based system. This methodology is complementary to classical solid-phase synthesis; individual columns are packed with resin-bound reagents and then linked in sequence and/or in parallel. In contrast to the traditional solid-phase approach, substrates are introduced in the mobile phase where they build up chemical complexity by percolating through the linked columns, ultimately eluting as the desired product.     

An iron-peroxo porphyrin complex: new synthesis and reactivity toward a Cu(II) complex giving a heme-peroxo-copper adduct

Side-on eta2-peroxo-iron porphyrins are strong nucleophiles. In cytochrome P450-like aromatase and other enzymes, such species are postulated as the active oxidants. In cytochrome c oxidase, hemea3-peroxo, hemea3-hydroperoxo, or hemea3-(mu-peroxo)-copper species are proposed as transient intermediates forming prior to O-O bond cleavage. In this report, we describe (1) a facile method for reduction of a heme-O2 species [(F8TPP)FeIII(O2-)(S)] (2), generating the ferric peroxo porphyrin complex [(F8TPP)FeIII(O22-)]- (3) (UV-vis, THF: lambdamax = 435 (Soret), 540(sh), 561; EPR: g = 8.7, 4.2), and (2) that this can be subsequently reacted with a ligand-copper(II) complex, [CuII(TMPA)-(CH3CN)](ClO4)2 (4), affording a heme-peroxo-copper heterobinuclear compound, [(F8TPP)FeII(O22-)-CuII(TMPA)](ClO4) (5). Generation of [(F8TPP)FeIII(O22-)]- (3) using cobaltocene as a one-electron reductant was monitored by UV-vis, EPR, and 1H NMR spectroscopies. Reaction between 3 and 4 was followed by UV-vis spectroscopy, and the product 5 could be precipitated and characterized. Coordination by copper(II) in 5 makes possible further reduction of the mu-peroxo complex by cobaltocene yielding the mu-oxo analogue, [(F8TPP)FeIII(O2-)-CuII(TMPA)](ClO4) (6).     

Studies toward the synthesis of roseophilin: lactam formation and Wittig/aldol methodology

In this communication, we introduce our retrosynthetic approach to the synthesis of roseophilin. An interesting, new Wittig/aldol methodology is described. Also discussed is macrocyclization of an azide acid to form an unsaturated lactam.     

Investigations into cluster formation with alkyl-tethered bis-calix[4]arenes

Abstract

Calix[4]arenes are versatile ligands capable of forming a wide range of cluster motifs when reacted with 3d, 4f or 3d/4f metal ions. Synthetic modification at the calix[4]arene methylene bridge offers a unique opportunity to explore cluster formation with these alternative building blocks. Here, we present the synthesis of a range of bis-calix[4]arenes that are tethered by alkyl chains, as well as exploratory structural studies into cluster-forming reactions. Single crystals were formed in four cases, and from the X-ray structures elucidated it is possible to conclude that sufficiently long alkyl tethers allow for the formation of established cluster topologies without disruption to the core coordination chemistry.     

Controllable synthesis of Cu2S nanocrystals and their assembly into a superlattice

Highly uniform Cu2S nanocrystals with controllable sizes and shapes (circular and elongated) have been synthesized through a novel water-oil interface confined reaction. They can self-assemble into highly ordered multilayer superlattices. By controlling the size and shape of building block nanocrystals, the packing symmetry of the superlattice can be engineered. For circular nanocrystals, both fcc and hcp multilayer superlattices are found in the sample. For elongated nanocrystals, they can also generate a close-packed layer and further stack into a multilayer superlattice. The dipole moment of the inner nanocrystals is useful for their stacking. This work provides a simple bottom-up approach to integrate nanocrystals, as well as to adjust the packing symmetry of the final superlattice, which may have potential applications for nanomaterials and nanodevices in the future.     

Investigations into a vessel of the Cyclades

Summary A Cyclade marble vessel has been investigated with regard to its content of fatty acids. TLC and GC techniques have been employed. Archaeological interpretation of the results is presented.Dedicated to Prof. Dr. G. Schulze on the occasion of his 60th birthday