拉曼光谱在固相有机合成中的应用

本文综述了近几年以来拉曼光谱在固相有机合成中的应用研究进展,分别介绍了近红外傅立叶变换和共焦显微两种拉曼光谱技术。近红外傅立叶变换拉曼光谱克服了荧光背景带来的干扰,可以用在固载试剂、催化剂的表征、固相有机反应的监测等方面,特别对于在无机载体上进行的有机反应的表征和检测方面具有很大的优势。共焦显微拉曼光谱具有特殊的空间分辨能力,适合对固相合成载体的结构进行表征,并可对载体内部反应活性位点的分布情况进行研究。     

Effects of porous polystyrene resin parameters on Candida antarctica lipase B adsorption, distribution, and polyester synthesis activity

Polystyrene resins with varied particle sizes (35 to 350-600 microm) and pore diameters (300-1000 A) were employed to study the effects of immobilization resin particle size and pore diameter on Candida antarctica Lipase B (CALB) loading, distribution within resins, fraction of active sites, and catalytic properties for polyester synthesis. CALB adsorbed rapidly (saturation time 相似文献   

Experimental investigation of nanoparticle dispersion by beads milling with centrifugal bead separation

A new type of beads mill for dispersing nanoparticles into liquids has been developed. The bead mill utilizes centrifugation to separate beads from nanoparticle suspensions and allows for the use of small sized beads (i.e. 15-30 microm in diameter). The performance of the beads mill in dispersing a suspension of titanium dioxide nanoparticle with 15 nm primary particles was evaluated experimentally. Dynamic light scattering was used to measure titania particle size distributions over time during the milling process, and bead sizes in the 15-100 microm range were used. It was found that larger beads (50-100 microm) were not capable of fully dispersing nanoparticles, and particles reagglomerated after long milling times. Smaller beads (15-30 microm) were capable of dispersing nanoparticles, and a sharp peak around 15 nm in the titania size distribution was visible when smaller beads were used. Because nanoparticle collisions with smaller beads have lower impact energy, it was found by X-ray diffraction and transmission electron microscopy that changes in nanoparticle crystallinity and morphology are minimized when smaller beads are used. Furthermore, inductively-coupled plasma spectroscopy was used to determine the level of bead contamination in the nanoparticle suspension during milling, and it was found that smaller beads are less likely to fragment and contaminate nanoparticle suspensions. The new type of beads mill is capable of effectively dispersing nanoparticle suspensions and will be extremely useful in future nanoparticle research.     

Production, analysis, and application of spatially resolved shells in solid-phase polymer spheres

Two-photon fluorescence microscopy has been used to interrogate the interior functionality of polymer resin beads. By employing this technique, the spatial distribution of the initial functionality contained within the polymer matrix has been determined. Spatially resolved, concentric shells were then produced synthetically in these polymer spheres via a series of protection/deprotection reactions in which two-photon fluorescence microscopy was employed to monitor each successive step. To demonstrate the potential utility of these techniques in combinatorial screening, a set of beads was prepared containing a unique tripeptide sequence in each of the three concentric shells within each individual bead. The set was then screened for the binding affinity of each tripeptide toward a fluorescent ligand.     

Pellicular expanded bed matrix suitable for high flow rates

A new type of expanded bed matrix with a heavy core of stainless steel covered with an agarose layer was prepared. Two bead size fractions, the smaller one (32-75 microm diameter) having a single particle core and the larger (75-180 microm diameter) with an agglomerate of stainless steel particles constituting the core, were chosen for further characterisation. The dispersion behaviour was determined both in packed bed and expanded bed modes by the retention time distribution method (RTD) and compared with the Streamline matrix (Amersham Pharmacia Biotech). The comparison turned out in favour of the new matrix. Flow rates as high as 3000 cm/h were used with the larger fraction, giving stable expanded beds with good mass transfer properties. The matrices were mechanically stable without any tendency to crack or peal, even after prolonged use.     

An alkylsilyl-tethered, high-capacity solid support amenable to diversity-oriented synthesis for one-bead, one-stock solution chemical genetics

The synthesis and use of an alkylsilyl-tethered large (500-600 microm) polystyrene resin (1) are disclosed. An optimized Suzuki coupling of bromine-functionalized polystyrene and a silicon-functionalized alkylborane generates the silicon-substituted polystyrene 1 in large scale (>100 g). Resin loading is accomplished by activation as the silyl triflate, which can accommodate even sterically encumbered secondary alcohols and phenols. Treatment with HF/pyridine for linker cleavage is mild, efficient, and amenable to an automated, large-scale distribution system. This platform delivers, minimally, 50 nmol of each small molecule derived from a diversity-oriented, split-pool synthesis on a per bead basis for use in both forward and reverse chemical genetic assays. This technology satisfies many requirements of a one bead-one stock solution approach to chemical genetics.     

Vibrational spectroscopic analysis of an amber necklace—a forensic historical study

The vibrational infrared spectroscopic analysis of an important historical necklace of 102 beads that are purported to be made of amber indicated strong signal characteristics of cellulose nitrate with dark green-coloured areas of a naphthylamine dye. Confocal Raman depth-profiling spectroscopy using a 785-nm laser excitation, a novel application first applied here for the analysis of inclusions in amber resin, confirmed that the beads were amber resin and that residues of cellulose nitrate, camphor plasticiser and a naphthylamine dyestuff were present in surface cracks and inclusions in the bead matrix. The bead stringing material was confirmed as cellulose, which was stained green in part with the dyestuff. Comparison of the Raman spectra of the amber beads with a resin database suggested that the amber was sourced from Northern England. The scientific evidence supports the stylistic opinion that the necklace is an important example that could date from the 19th Century and that efforts had been made to coat it with a synthetic dyed polymer; this provides a rather unusual example of the chemical masking of a genuine article—a procedure that renders the article of particular interest.     

Separation of transition metals on a poly-iminodiacetic acid grafted polymeric resin column with post-column reaction detection utilising a paired emitter-detector diode system

The selectivity, retention and separation of transition metals on a short (2 mm x 50 mm) column packed with a poly-iminodiacetic acid functionalised polymer 10 microm resin (Dionex ProPac IMAC-10) are presented. This stationary phase, typically used for the separation of proteins, is composed of long chain poly-iminodiacetic acid groups grafted to a hydrophilic layer surrounding a 10 microm polymeric bead. Through the use of a combination of a multi-step pH and picolinic acid gradient, the separation of magnesium, iron, cobalt, cadmium, zinc, lead and copper was possible, followed by post-column reaction with 4-(2-pyridylazo) resorcinol (PAR) and absorbance detection at 510 nm using a novel and inexpensive optical detector, comprised of two light emitting diodes with one acting as a light source and the other as a detector. Column efficiency for selective transition metals was in excess of N=10,000, with the baseline separation of seven metal cations in <3 min possible under optimised conditions. Detection limits of between 5 and 81 microg/L were possible based upon a 50 microL injection volume.     

A UV resonance Raman (UVRR) spectroscopic study on the extractable compounds of Scots pine (Pinus sylvestris) wood. Part I: lipophilic compounds

The wood resin in Scots pine (Pinus sylvestris) stemwood and branch wood were studied using UV resonance Raman (UVRR) spectroscopy. UVRR spectra of the sapwood and heartwood hexane extracts, solid wood samples and model compounds (six resin acids, three fatty acids, a fatty acid ester, sitosterol and sitosterol acetate) were collected using excitation wavelengths of 229, 244 and 257 nm. In addition, visible Raman spectra of the fatty and resin acids were recorded. Resin compositions of heartwood and sapwood hexane extracts were determined using gas chromatography. Raman signals of both conjugated and isolated double bonds of all the model compounds were resonance enhanced by UV excitation. The oleophilic structures showed strong bands in the region of 1660-1630 cm(-1). Distinct structures were enhanced depending on the excitation wavelength. The UVRR spectra of the hexane extracts showed characteristic bands for resin and fatty acids. It was possible to identify certain resin acids from the spectra. UV Raman spectra collected from the solid wood samples containing wood resin showed a band at approximately 1650 cm(-1) due to unsaturated resin components. The Raman signals from extractives in the resin rich branch wood sample gave even more strongly enhanced signals than the aromatic lignin.     

In search of higher sensitivity: Pu isotopic analysis

Summary Thermal ionization mass spectrometry (TIMS) is an effective method for isotopic and ultra-sensitivity determination of plutonium. This project aims at improving the National Institute of Standards and Technology (NIST) TIMS system sensitivity for the analysis of plutonium from environmental samples. The TIMS detection limits for direct, electrodeposition, and resin bead source loading techniques were determined by systematically varying the amount of plutonium loaded on the rhenium filament. It has been shown in our preliminary work that the resin bead could produce a stable TIMS ion beam for as long as 6 h period with ?10⁸ Pu atoms loaded onto a single resin bead.     

Surface-enhanced Raman spectroscopic-encoded beads for multiplex immunoassay

A new type of encoded bead, which uses surface-enhanced Raman scattering (SERS), is described for multiplex immunoassays. Silver nanoparticles were embedded in sulfonated polystyrene (PS) beads via a polyol method, and they were used as SERS-active substrates. Raman-label organic compounds such as 4-methylbenzenethiol (4-MT), 2-naphthalenethiol (2-NT), and benzenethiol (BT) were then adsorbed onto the silver nanoparticles in the sulfonated PS bead. Although only three kinds of encoding have been demonstrated here, various combinations of these Raman-label organic compounds have the potential to give a large number of tags. The Raman-label-incorporated particles were then coated with a silica shell using tetraethoxyorthosilicate (TEOS) for chemical stability and biocompatibility. The resulting beads showed unique and intense Raman signals for the labeled organic compounds. We demonstrated that SERS-encoded beads could be used for multiplex detection with a model using streptavidin and p53. In our system, the binding event of target molecules and the type of ligand can be simultaneously recognized by Raman spectroscopy using a single laser-line excitation (514.5 nm).     

Resonant Raman scattering characterization of carbon nanotubes grown with different catalysts

Single-walled carbon nanotube samples produced in the presence of different combinations of metal catalysts have been studied by resonant Raman spectroscopy. The diameter distribution of different samples has been determined by analysis of the laser excitation energy dependence of the tangential modes associated with metallic nanotubes. These modes are resonantly enhanced over a narrow range of the exciting energies, which shifts for different samples. The Raman cross-section expression has been used to fit the experimental Raman excitation profiles. This procedure was used to determine the mean value and the width of the distribution of diameters within each sample.     

Patterned self-assembled beads in silicon channels.

A novel technique enabling selective bead trapping in microfluidic devices without the use of physical barriers is presented in this paper. It is a fast, convenient and simple method, involving microcontact printing and self-assembly, that can be applied to silicon, quartz or plastic substrates. In the first step, channels are etched in the substrate. The surface chemistry of the internal walls of the channels is then modified by microcontact printing. The chip is submerged in a bead slurry where beads self-assemble based on surface chemistry and immobilize on the internal walls of the channels. Silicon channels (100 microm wide and 50 microm deep) have been covered with monolayers of streptavidin-, amino- and hydroxy-functionalized microspheres and resulted in good surface coverage of beads on the channel walls. A high-resolution pattern of lines of self-assembled streptavidin beads, as narrow as 5 microm, has also been generated on the bottom of a 500 microm wide and 50 microm deep channel. Flow tests were performed in sealed channels with the different immobilized beads to confirm that the immobilized beads could withstand the forces generated by water flowing in the channels. The presented results indicate that single beads can be precisely positioned within microfluidic devices based on self-assembly which is useful as screening and analysis tools within the field of biochemistry and organic chemistry.     

Molecular state and distribution of fullerenes entrapped in sol-gel samples

A novel synthetic method that can encapsulate fullerene molecules (pure C60, pure C70, or their mixture) over a wide range of concentrations ranging from micromolar to millimolar in hybrid glass by a sol-gel method without any time-consuming, complicated, and unwanted extra steps (e.g., addition of a surfactant or derivatization of the fullerenes) has been successfully developed. The molecular state and distribution of encapsulated fullerene molecules in these sol-gel samples were unequivocally characterized using newly developed multispectral imaging techniques. The high sensitivity (single-pixel resolution) and ability of these instruments to record multispectral images at different spatial resolutions (approximately 10 microm with the macroscopic instrument and approximately 0.8 microm with the microscopic instrument) make them uniquely suited for this task. Specifically, the imaging instruments can be used to simultaneously measure multispectral images of sol-gel-encapsulated C60 and C70 molecules at many different positions within a sol-gel sample in an area either as large as 3 mm x 4 mm (with the macroscopic imaging instrument) or as small as 0.8 microm x 0.8 microm (with the microscopic instrument). The absorption spectrum of the fullerene molecule at each position can then be calculated either by averaging the intensity of a 15 x 15 square of pixels (which corresponds to an area of 3 mm x 4 mm) or from the intensity of a single pixel (i.e., an area of about 0.8 microm x 0.8 microm), respectively. The molecular state and distribution of fullerene molecules within sol-gel samples can then be determined from the calculated spectra. It was found that spectra of encapsulated C60 and C70 measured at five different positions within a sol-gel sample were similar not only to one another but also to spectra measured at six different times during the sol-gel reaction process (from t = 0 to 10 days). Furthermore, these spectra are similar to the corresponding spectra of monomeric C60 or C70 molecules in solution. Similarly, spectra of sol-gel samples containing a mixture of C60 and C70 were found to be the same at five different positions, as well as similar to spectra calculated from an average of the spectra of C60 and C70 either encapsulated in a sol-gel or in solution. It is evident from these results that C60 and C70 molecules do not undergo aggregation upon encapsulation into a sol-gel but rather remain in their monomeric state. Furthermore, entrapped C60 and C70 molecules in their monomeric state were distributed homogeneously throughout the entire sol-gel samples. Such a conclusion can be readily, quickly, and easily obtained, not with traditional spectroscopic techniques based on the use of a single-channel detector (absorption, fluorescence, infrared, Raman) but rather with the newly developed multispectral imaging technique. More importantly, the novel synthetic method reported here makes it possible, for the first time, to homogenously entrap monomeric fullerene molecules (C60, C70, or their mixture) in a sol-gel at various concentrations ranging from as low as 2.2 mM C60 (or 190 microM C70) to as high as 4.2 mM C60 (or 360 microM C70).     

Raman spectroscopy and imaging of ultralong carbon nanotubes

Raman spectroscopy and confocal Raman imaging with 514 nm excitation was performed on recently developed ultralong carbon nanotubes grown by the "fast-heating" chemical vapor deposition (CVD) method. The ultralong nanotubes are found to consist of both semiconducting and metallic types, with spectra that are consistent with the nanotubes being single walled. Characterization of nanotube diameters shows that short nanotubes appearing near the sample catalyst region have a broader distribution than is observed for the ultralong nanotubes. The narrow diameter distribution is determined by uniformity of catalyst particle size and gives additional evidence for the proposed "kite" mechanism for long nanotube growth. Raman imaging was performed over large length scales (up to 140 microm). Imaging reveals the ultralong nanotubes to be of high quality, with a very low defect density. Variations in G-band frequencies and intensity demonstrate the occurrence of minor structural changes and variations in nanotube-substrate interaction along the length of the nanotubes. Evidence also demonstrates that larger structural changes resulting in a full chirality change can occur in these nanotube types to produce a metal-to-semiconductor intramolecular junction.     

Analysis of Raman and infrared spectra of poly(vinylidene fluoride) irradiated by KrF excimer laser

In this paper, the micro-mechanics of electrical conductivity increases of poly(vinylidene fluoride) (PVDF) samples induced by KrF excimer laser was analyzed by Raman spectra and infrared spectra. The irradiated layer of the samples was observed by the method of Raman mapping and scanning electron microscope and the thickness of the conducting layer of PVDF samples was determined to be about 6.5 microm. Moreover, the surface microstructure of the irradiated PVDF samples was discussed in the light of scanning electron microscope, Raman spectra and Raman mapping.     

Transient UV Raman spectroscopy finds no crossing barrier between the peptide alpha-helix and fully random coil conformation.

Transient UV resonance Raman measurements excited within the amide pi --> pi transitions of a 21 unit alpha-helical peptide has for the first time determined a lower bound for the unfolding rate of the last alpha-helical turn to form a fully random coil peptide. A 3 ns T-jump is generated with 1.9 microm laser pulses, which are absorbed by water. Subsequent 3 ns 204 nm UV pulses excite the amide Raman spectra at delay times between 3 ns and 1 ms, to monitor the peptide conformational evolution. We find approximately 180 ns relaxation times which result in a rate constant of >5 x 10(6) s(-1) for unfolding of the last alpha-helical turn. Our data are inconsistent with slow alpha-helix nuclei melting.     

Real-Time Monitoring of the Catalytic Oxidation of Alcohols to Aldehydes and Ketones on Resin Support by Single-Bead Fourier Transform Infrared Microspectroscopy

Catalytic oxidations of primary, benzylic, and secondary alcohols to aldehydes and ketone using tetra-n-propylammonium perruthenate (TPAP) were carried out on resin supports for the first time. The reaction time course, percent conversion, and influence of catalyst amount have been determined by analyzing IR spectra taken directly on a single resin bead in real time. Using 0.2 equiv of TPAP, a 92-97% conversion of alcohol to aldehyde or ketone has been achieved in 0.7-4 h based on the rates (rate constants (1.9 x 10(-)(4))-(2.5 x 10(-)(3)) s(-)(1)) of disappearance and appearance of IR bands characteristic for alcohol, aldehyde, and ketone. The rapid adaptation of this oxidation method for solid-phase synthesis demonstrates that single-bead FTIR microspectroscopy is a powerful method for facilitating the time-consuming reaction optimization stage of combinatorial chemistry.     

Miscibility behavior of ethylene/vinyl acetate and C5 petroleum resin by FTIR imaging.

FTIR microscopic imaging was used to investigate the miscibility behavior of ethylene/vinyl acetate copolymer (EVA) and C5 petroleum resin. Images with an area of 500 x 500 microm(2) were collected in the reflection mode. The miscibility was characterized by probing the spatial distribution of the carbonyl group (C=O) of EVA in the whole images. It was found that a 1:1 hot-melt mixture of EVA and C5 resin showed a good miscibility behavior. For two different EVA copolymers, one with 18% vinyl acetate (VAc) content showed a better miscibility behavior than that with 28% VAc content. Our results demonstrated that this method allowed a direct, convenient and nondestructive visualization. This developed technique promises to become a powerful tool for studying the miscibility behavior of composite materials.     

Carbon dioxide emulsion assisted loading of polymer microspheres toward sustained release materials

An organic solvent-free method for encapsulating progesterone at high loadings within micron-sized inert latex polymer beads is reported. This approach makes use of a polymeric surfactant to emulsify carbon dioxide into an aqueous latex suspension. In this way, preformed approximately 4 microm polystyrene (PS) microparticles surface-grafted with poly(N-vinylpyrrolidone) (PVP) were plasticized and swollen followed by rapid partitioning of progesterone into the polymer matrix. The as-prepared polystyrene beads incorporated over 10% progesterone by weight while maintaining their initial size and morphological uniformity. Dissolution experiments were also carried out to obtain the release profile of progesterone entrapped within the PVP/PS particles.