Split-pool method for synthesis of solid-state material combinatorial libraries

The synthesis and analysis of inorganic material combinatorial libraries by the split-pool bead method were demonstrated at the proof-of-concept level. Millimeter-size spherical beads of porous gamma-alumina, a commonly used support material for heterogeneous catalysts, were modified with Al(13)O(4)(OH)(24)(H(2)O)(12)(7+) cations in order to promote irreversible adsorption of the anionic fluorescent dyes Cascade Blue, Lucifer Yellow, and Sulforhodamine 101. The compositions of individual beads were easily determined through three split-pool cycles using a conventional fluorescence plate reader. Small split-pool material libraries were made by adsorbing noble metal salts (H(2)PtCl(6), H(2)IrCl(6), and RhCl(3)) into the beads. Analysis of these beads by micro-X-ray fluorescence showed that quantitative adsorption of metal salts without cross-contamination of beads could be achieved at levels (0.3 wt % metal loading) relevant to heterogeneous catalysis. The method offers the potential for synthesis of rather large libraries of inorganic materials through relatively simple benchtop split-pool chemistry.     

Combinatorial synthesis of carbon nanotubes by the catalytic chemical vapor deposition method

Summary Bimetallic (Fe-Co) catalyst samples prepared from different precursors over various supports were tested in carbon nanotube (CNT) production. In order to quicken the evaluation of the performance of the catalysts a combinatorial arrangement was used.</o:p>     

Combinatorial synthesis and hydrogenation of Mg/Al libraries prepared by electron beam physical vapor deposition

We have grown thin film libraries of the Mg-Al system using a high-throughput synthesis methodology that combines the sequential deposition of pure elements (Mg and Al) by an electron-beam (e-beam) evaporation technique and the use of a special set of moving shadow masks. This novel mask has been designed to simultaneously prepare four identical arrays of different compositions that will permit the characterization of the same library after several treatments. Wavelength dispersive spectroscopy (WDS) and micro-X-ray diffraction have been used as high-throughput screening techniques for the determination of the composition and structure of every member of the library in the as-deposited state and after hydrogenation at 1 atm of H2 during 24 h at three different temperatures: 60, 80, and 110 degrees C. We have analyzed the influence of the Mg-Al ratio on the hydrogenation of magnesium, as well as on the appearance of complex hydride phases. We have also found that aluminum can act as a catalyzer for the hydrogenation reaction of magnesium.     

Purification of high-throughput organic synthesis libraries by counter-current chromatography

Experiments were performed to evaluate whether counter-current chromatography (CCC) could function as an alternative purification method to reversed-phase high-performance liquid chromatography (RP-HPLC) and normal-phase supercritical fluid chromatography (SFC). RP-HPLC and SFC are the routine methods currently used in our high-throughput purification (HTP) facility for the purification of high-throughput organic synthesis (HTOS) libraries and medicinal chemistry reaction mixtures. Pre-equilibration of the solvent mixture layers was not mandatory for effective chromatography when hexanes–ethyl acetate–methanol–water (HEMW) solvent mixtures were used. Key to the use of CCC for high-throughput applications is the ability to effectively select a solvent system appropriate to each library member. Pilot-scale CCC elution time was used to estimate a starting solvent ratio and RP-HPLC retention time was then used to adjust solvent ratios within a particular library. It was also found that dimethyl sulfoxide (DMSO) and DMSO–methanol were suitable as sample injection solvents when using the HEMW solvent systems.     

硅纳米线的化学气相沉积法合成

硅纳米线是近十几年来在纳米科学与技术领域快速发展的一种重要材料．通过精细的结构设计与材料合成,硅纳米线在生物传感、锂离子电池、太阳能电池和光电化学等领域展示出良好的应用前景．化学气相沉积（CVD）法是一大类重要的自下而上合成硅纳米线方法．本文简介了CVD法合成硅纳米线的主要进展,包括具有单一结构和复合结构的硅纳米线的合成．其中,单一结构的硅纳米包括本征（无掺杂）、掺杂和超长的硅纳米线;复合结构的硅纳米线包括轴向异质结、径向异质结、转折结构和树枝状结构的硅纳米线．     

A novel approach to high-throughput quality control of parallel synthesis libraries

Combinatorial chemistry is a powerful tool to enhance drug discovery efforts in the pharmaceutical industry. One type of combinatorial chemistry, parallel synthesis, is now widely used to prepare numerous compounds of structural diversity. A novel high-throughput method for quality control of parallel synthesis libraries has been developed. The method uses flow injection MS, for proof of structure and estimation of purity, and a novel direct injection CLND technique for quantitation of amount. Following the synthesis of a small molecule library, compounds analyzed using this technique were characterized by mass spectrometry, and an accurate concentration of the compound was assessed by CLND. Characterization of one compound is completed in 60 s, allowing for up to 1000 compounds to be analyzed in a single day. The data is summarized using pass/fail criteria using internally developed software.     

Chemical vapor deposition synthesis of tunable unsubstituted polythiophene

Despite having exceptional electroactive properties, applications of unsubstituted polythiophene (PTh) have been limited due to its insolubility. To overcome this challenge, we have employed oxidative chemical vapor deposition (oCVD) as a unique liquid-free technique to enable the oxidative polymerization of PTh using thiophene as the starting monomer and vanadium oxytrichloride as an effective vaporizable oxidant initiator. Vibrational and phototelectron spectroscopy indicated the formation of unsubstituted polythiophene. Cyclic voltammetry revealed its electrochromic behavior in solution. Significantly, polymer conjugation length and electrical conductivity can be tuned by controlling oCVD process variables. Polymerization is found to be adsorption-limited, so by providing sufficient monomer and limiting the amount of initiator at the growth surface, PTh is believed to be formed through α-α thiophene linkages.     

2D and 3D spatially addressed arrays for high-throughput automated synthesis of combinatorial libraries

One of the key elements in the drug discovery process is the use of automation to synthesize libraries of compounds for biological screening. The "split-and-mix" approaches in combinatorial chemistry have been recognized as extremely powerful techniques to access large numbers of compounds, while requiring only few reaction steps. However, the need for effective encoding/deconvolution strategies and demands for larger amounts of compounds have somewhat limited the use of these techniques in the pharmaceutical industry. In this paper, we describe a concept of directed sort and combine synthesis with spatially arranged arrays of macroscopic supports. Such a concept attempts to balance the number of reaction steps, the confidence in compound identity, and the quantity of synthesized compounds. Using three-dimensional arrays of frames each containing a two-dimensional array of macroscopic solid supports, we have conceptualized and developed a modular semiautomated system with a capacity of up to 100 000 compounds per batch. Modularity of this system enables flexibility either to produce large diverse combinatorial libraries or to synthesize more focused smaller libraries, both as single compounds in 12-15 micromol quantities. This method using sortable and spatially addressed arrays is exemplified by the synthesis of a 15 360 compound library.     

A catalytic chemical vapor deposition synthesis of double-walled carbon nanotubes over metal catalysts supported on a mesoporous material

Double-walled carbon nanotubes (DWNTs) have been synthesized by catalytic chemical vapor deposition (CCVD) over supported metal catalysts decomposed from Fe(CH₃COO)₂ and Co(CH₃COO)₂ on mesoporous silica. Bundles of tubes with relatively high percentage of DWNTs, in areas where tubular layered structures could be clearly resolved, have been observed by transmission electron microscopy (TEM). In other areas, crystal-like alignment of very uniform DWNTs was observed for the first time, suggesting that mesoporous silica might play a templating role in guiding the initial nanotube growth. In addition, compatible with nano-electronics research, bridging of catalytic islands by DWNTs has also been demonstrated.     

Chemical vapor transport and solid-state exchange synthesis of new copper selenite bromides

A new dimorphic copper selenite bromide, Cu₅(SeO₃)₄Br₂ was obtained via chemical transport reactions. α-Cu₅(SeO₃)₄Br₂, monoclinic (1m) and β-Cu₅(SeO₃)₄Br₂, triclinic (1a) polymorphs were produced simultaneously upon reaction of amorphous, partially dehydrated copper selenite and copper bromide. 1m is similar to Cu₅(SeO₃)₄Cl₂, whereas 1a is distantly related to Ni₅(SeO₃)₄Br₂ and Co₅(SeO₃)₄Br₂. Attempts to reproduce synthesis of 1a via exchange reaction between Na₂SeO₃ and CuBr₂ resulted in a new Na₂[Cu₇O₂](SeO₃)₄Br₄ (2). Current study demonstrates for the first time, that both chemical vapor and exchange reactions can be employed in preparation of new selenite halides.     

UV-triggered main-component fraction collection method and its application for high-throughput chromatographic purification of combinatorial libraries

A maximum-seeking, algorithm-driven fraction collection method was developed to support high-throughput chromatographic purification, which provides new possibilities for off-line high-performance liquid chromatography mass spectroscopy (HPLC/MS) quality control experiments. The method is based on manipulation of a six-port valve that is installed downstream from the UV detector and equipped with a fraction collector loop. The detector signal is monitored by a programmable microcontroller that controls the state of the fraction collector valve. After detecting a chromatographic peak, the appropriate fraction is stored in the collector loop. The height of the next peak is compared to the previous one (using a maximum-seeking algorithm) and, depending on the result, the collected fraction is or is not exchanged with the new one. At the end of the run, the stored UV main component is pumped into the external fraction vial. This configuration was used for chromatographic purification of large compound libraries (the results of the purification of 5324 compounds are reported here), as well as for high-throughput off-line HPLC quality control experiments, where the collected main component fractions of an analytical-scale separation were subjected to further mass spectrometric molecular weight verification.     

Directed-sorting method for synthesis of bead-based combinatorial libraries of heterogeneous catalysts

The synthesis and analysis of inorganic material combinatorial libraries by a directed-sorting, split-pool bead method was demonstrated. Directed-sorting, split-pool, metal-loaded libraries were synthesized by adsorbing metal salts (H2PtCl6, SnCl2, CuCl2, and NiCl2) and metal standards (Pt, Cu, Ni in HCl) onto 2-mg porous gamma-alumina beads in 96- or 384-well plates. A matrix algorithm for the synthesis of bead libraries treated each bead as a member of a row or column of a given matrix. Computer simulations and manual tracking of the sorting process were used to assess library diversity. The bead compositions were analyzed by energy-dispersive X-ray spectroscopy, X-ray fluorescence spectroscopy, electron probe microanalysis, inductively coupled plasma atomic emission spectroscopy, and inductively coupled plasma mass spectroscopy. The metal-loaded beads were analyzed by laser-activated membrane introduction mass spectroscopy (LAMIMS) for catalytic activity using methylcyclohexane dehydrogenation to toluene as a probe reaction. The catalytic activity of individual beads that showed minimal (approximately 20% of that of Pt on alumina) to high conversion could be determined semiquantitatively by LAMIMS. This method, therefore, provides an alternative to screening using microreactors for reactors that employ catalysts in the form of beads. The directed-sorting method offers the potential for synthesis of focused libraries of inorganic materials through relatively simple benchtop split-pool chemistry.     

Synthesis of high-purity GaP nanowires using a vapor deposition method

High-purity gallium phosphide (GaP) nanowires were successfully synthesized on the nickel monoxide (NiO) or the cobalt monoxide (CoO) catalyzed alumina substrate by a simple vapor deposition method. To synthesize the high-purity GaP nanowires, the mixture source of gallium (Ga) and GaP powder was directly vaporized in the range of 850–1000 °C for 60 min under argon ambient. The diameter of GaP nanowires was about 38–105 nm and the length was up to several hundreds of micrometers. The GaP nanowires have a single-crystalline zinc blend structure and reveal the core-shell structure, which consists of the GaP core and the GaPO₄/Ga₂O₃ outer layers. We demonstrate that the mixture of Ga/GaP is an ideal source for the high-yield GaP nanowires.     

Chemical vapor infiltration method for deposition of gold nanoparticles on porous alumina supports

Knudsen’s effusion method with mass spectral analysis of the composition of the gas phase was used to measure the temperature dependence of the saturated vapor of several (CH₃)₂AuL chelate complexes and to determine the thermodynamic parameters of their sublimation. Based on the results of this study, conditions for chemical vapor deposition of gold using dimethylgold(III) chelates were chosen. Gold nanoparticles were synthesized by chemical vapor deposition (infiltration) of (CH₃)₂Au(acac) on porous granules of γ-Al₂O₃ with subsequent calcination in air at 325°C. Particle size and the chemical state of gold in Au/γ-Al₂O₃ systems were evaluated by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). A vapor infiltration procedure is suggested to prepare metallic gold particles ≤5 nm in diameter from Au/γ-Al₂O₃. It is shown that Au/γ-Al₂O₃ systems obtained by chemical vapor infiltration and containing small gold crystallites possess high catalytic activity in CO oxidation reactions at 40°C.     

Preparative high-performance liquid chromatography-mass spectrometry for the high-throughput purification of combinatorial libraries

Accurate results for the testing of combinatorial libraries necessitates high purity of the library members. Therefore, combinatorial libraries derived from a combinatorial solution or solid-phase synthesis often require the purification of compounds that do not achieve a certain purity threshold. This study describes that preparative high-performance liquid chromatography (HPLC)-mass spectrometry (MS) is the method of choice for the purification of large arrays of diverse compounds. The adoption of this technology to the workflow of a solution phase combinatorial chemistry laboratory producing more than 20,000 compounds per year is described. Furthermore, the setup and logistics are discussed as well as the purity achievable for large libraries. Efficiency, speed, quality, and universality of preparative HPLC-MS are presented in detail for a library of 140 compounds, including data logistics and downstream processes as well.     

Size-tunable synthesis of tetrapod-like ZnS nanopods by seed-epitaxial metal-organic chemical vapor deposition

Single-crystalline tetrapod-like ZnS nanopods were synthesized by a one-step seed-epitaxial metal-organic chemical vapor deposition (MOCVD) approach using cubic CdSe nanocrystals as the seeds. The diameters of the ZnS tetrapods can be easily tuned by changing the distances between the substrates and precursors. A possible growth mechanism is discussed on the basis of the heterostructure epitaxial growth. The ZnS tetrapod has a zinc CdSe nanocrystal core at the center with four wurtzite ZnS arms growing out from the core along four [0001] directions. Due to the lower temperature and versatility, this controllable seed-epitaxial method has potential as a general means of forming complex branching structures and may also offer opportunities for applications as building blocks for optoelectronic devices.     

Selective chemical vapor deposition synthesis of double-wall carbon nanotubes on mesoporous silica

Double-wall carbon nanotubes (DWNTs) have been selectively synthesized over Fe/Co loaded mesoporous silica by catalytic chemical vapor deposition of alcohol. Several silica materials with desired pore diameter and morphology have been investigated for the DWNT growth. The diameter distribution and selectivity of the DWNT are found to depend on the reaction temperature, pore size, and thermal stability of the support material. A high-yield synthesis of DWNTs has been achieved at 900 degrees C over high-temperature stable mesoporous silica. The outer diameter of DWNTs is found to be in the range of 1.5-5.4 nm with a "d" spacing of 0.38 +/- 0.02 nm between inner and outer layers, which is much larger than those of multiwall carbon nanotubes.