共查询到20条相似文献,搜索用时 31 毫秒
1.
López-Mejías V Knight JL Brooks CL Matzger AJ 《Langmuir : the ACS journal of surfaces and colloids》2011,27(12):7575-7579
The phase-selective crystallization of acetaminophen (ACM) using insoluble polymers as heteronuclei was investigated in a combined experimental and computational effort to elucidate the mechanism of polymer-induced heteronucleation (PIHn). ACM heteronucleates from supersaturated aqueous solution in its most thermodynamically stable monoclinic form on poly(n-butyl methacrylate), whereas the metastable orthorhombic form is observed on poly(methyl methacrylate). When ACM crystals were grown through vapor deposition, only the monoclinic polymorph was observed on each polymer. Each crystallization condition leads to a unique powder X-ray diffraction pattern with the major preferred orientation corresponding to the crystallographic faces in which these crystal phases nucleate from surfaces of the polymers. The molecular recognition events leading to these outcomes are elucidated with the aid of computed polymer-crystal binding energies using docking simulations. This investigation illuminates the mechanism by which phase selection occurs during the crystallization of ACM using polymers as heteronuclei, paving the way for the improvement of methods for polymorph selection and discovery based on heterogeneous nucleation promoters. 相似文献
2.
Polymorphism - integrated approach from high-throughput screening to crystallization optimization 总被引:3,自引:0,他引:3
Hilfiker R. Berghausen J. Blatter F. Burkhard A. De Paul S. M. Freiermuth B. Geoffroy A. Hofmeier U. Marcolli C. Siebenhaar B. Szelagiewicz M. Vit A. von Raumer M. 《Journal of Thermal Analysis and Calorimetry》2003,73(2):429-440
Crystal structure (polymorphism) as well as crystal shape (morphology) and size have a huge practical and commercial impact
on active substances all the way from research to manufacture of the final product. For an optimal development process, it
is important to have an integrated approach to these issues ranging from a systematic polymorphism screening to a controlled
scale-up of the crystallization process. The polymorphism program has to be tailored according to the development stage. Particularly
suitable for an early development stage is a high-throughput polymorphism screening, which is the basis for a more thorough
investigation if the product proceeds further in development. Such a comprehensive polymorphism investigation involves further
crystallization experiments and extensive physicochemical characterization of the various forms. In this article the high-throughput
polymorphism screening method that we have developed is described. Using carbamazepine as an example, the power of this high-throughput
polymorphism screening system is demonstrated. Not only were all published forms found, but also new forms were identified.
In the second part of the article, important considerations for crystallization optimization are discussed, again using the
example of carbamazepine.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
3.
Xiao Lu Zhiji Luo Ruili Huang Donald C. Lo Dr. Wenwei Huang 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(50):e202201421
Detecting the formation of new chemical bonds in high-throughput synthesis is limited by the efficiency and scalability of reaction product detection, as conventional methods for isolating product from reaction mixtures are time consuming and labor intensive. Here, we report a miniaturizable purification method that enables the rapid, high-throughput isolation of quaternary ammonium-tagged products from reaction mixtures with excellent purity using inexpensive equipment that easily can be set up in a typical organic chemistry laboratory. This novel purification technique enabled us to establish a high-throughput reaction discovery platform. We validated this platform in a screen of 1536 reactions, and one previously unreported transformation was identified. 相似文献
4.
Anderson JE Moore S Tarczynski F Walker D 《Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy》2001,57(9):1793-1808
This work describes the use of UV/visible spectroscopy and calorimetry to follow the onset of crystallization of a commercially available compound, N(1)-2-(thiazolyl)sulfanilamide (sulfathiazole), during crystallization reactions performed using an automated reaction platform. Sulfathiazole has been the subject of numerous publications through which considerable confusion about the morphic form is apparent. This work does not attempt to investigate exhaustively the polymorph issue, but rather to exploit the use of the HEL auto-MATE for monitoring the onset of crystal formation. Real-time calorimetry and UV-Vis spectroscopy are compared as tools for determining the onset of crystallization. Subsequently, differential scanning calorimetry, dispersive Raman, and infrared spectroscopy analysis serve to identify the crystal forms generated by the HEL auto-MATE. A solvent-anti-solvent matrix and several bench-top crystallization experiments were performed to supplement the investigation in terms of generating the desired polymorphs. 相似文献
5.
Here, we demonstrated a mini-pillar based multi-channel electrochemical platform that can efficiently adjust multiple electrochemical deposition parameters in the microdroplet arrays to control and predict the final structures of silver nanomaterials. Each mini-pillar is capable of anchoring microdroplet to form a separate microreactor, and the electrodes are integrated to achieve a multi-channel electrochemical electrodeposition platform. We systematically investigated the multiple deposition parameters of silver nanostructures and summarized the relevant experience of electrochemical silver deposition to guide silver nanostructure preparation. Such the mini-pillar based microdroplet platform provides an approach for further high-throughput and intelligent nanomaterial fabrication. 相似文献
6.
The discovery and selective production of crystalline polymorphs, an outstanding problem in solid-state chemistry, is of great importance industrially in, for example, the manufacture of pharmaceuticals and pigments. Despite considerable efforts, no reliable method exists to produce all of the stable polymorphs of a given compound. Herein, we report methodology to control the phenomenon of crystal polymorphism through the use of diverse libraries of polymer heteronuclei including both commercially available polymers and combinatorially synthesized cross-linked polymers. This new approach for exploring polymorph space offers the advantage of high throughput crystallization to discover multiple polymorphs combined with the ability to selectively produce a given form from a single solvent and temperature condition by simply varying the nature of the polymer substrate. This technique is successfully demonstrated on the pharmaceuticals acetaminophen, sulfamethoxazole, and carbamazepine and on the pharmaceutical intermediate 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY). High throughput screening, accomplished by optical microscopy and Raman spectroscopy, identified the selective production of the two stable polymorphs of acetaminophen and all six stable forms of ROY. Furthermore, one new form of carbamazepine and two new forms of sulfamethoxazole were discovered; in these cases, single crystals were obtained enabling the structural characterization of two new tetramorphic systems. 相似文献
7.
Transformation of metastable forms of acetaminophen studied by thermal Fourier transform infrared (FT-IR) microspectroscopy 总被引:3,自引:0,他引:3
A novel Fourier transform infrared (FT-IR) microspectroscopy equipped with a micro hot stage (thermal FT-IR microscopic system) was used to quickly study the phase transformation of acetaminophen polymorphs by a one-step process. Acetaminophen was sealed in KBr disc on the first and second heating processes under this system. The results indicate that the contour IR profile of form I acetaminophen in the first heating process changed dramatically only near 165 degrees C, but in the re-heating process exhibited a considerable alteration in peak intensity, band width and position near the temperatures at 85, 118 and 153 degrees C. A glassy form of acetaminophen was obtained after rapidly cooling the melted acetaminophen from 200 to 25 degrees C. The glassy acetaminophen was recrystallized at 85 degrees C to transform to the form III of acetaminophen in the reheating process, and then transformed to its form II near 118 degrees C. The thermal FT-IR microscopic system is a simple, quick and timesaving tool for investigation of the thermo-dependent molecular structure of acetaminophen polymorphs in the processes of recrystallization and polymorphic transition. 相似文献
8.
Microfluidic synthesis of multifunctional Janus particles for biomedical applications 总被引:2,自引:0,他引:2
Multifunctional Janus particles have a variety of applications in a wide range of fields. However, to achieve many of these applications, high-throughput, low-cost techniques are needed to synthesize these particles with precise control of the various structural/physical/chemical properties. Microfluidics provides a unique platform to fabricate Janus particles using carefully controlled liquid flow in microfluidic channels to form Janus droplets and various types of solidification methods to solidify them into Janus particles. In this Focus article, we summarize the most recent representative works on Janus particle fabrication in microfluidics. The applications of Janus particles in biomedical areas are emphasized. We believe that microfluidics-enabled multifunctional Janus particles could resolve multiple prevalent issues in biomedicine (e.g., disease monitoring at an early stage, high-throughput bioassays, therapeutic delivery) if persistent effort and collaboration are devoted to this direction. 相似文献
9.
基于X射线晶体学的蛋白质结构解析主要依赖于大规模结晶条件筛选获得的高衍射分辨率的蛋白质晶体。近年来,自动化、高通量的液体操控技术和相关仪器的快速发展为蛋白质结晶筛选提供了高效、可靠的研究手段,显著推动了蛋白质结构生物学的研究。文章综述了蛋白质结晶筛选的自动化液体处理技术的发展,包括移液器、注射泵、同步纳升定量吸取注射、喷墨打印、超声喷射以及微流控等技术。文章详细介绍了各技术所对应的典型商品化仪器及其在蛋白质结晶筛选中的应用。此外,文章还介绍了集成多孔板的储存和操控、编码扫描、环境控制和软件管理等诸多功能的一体化液体操纵平台。 相似文献
10.
Rapid catalyst identification for the synthesis of the pyrimidinone core of HIV integrase inhibitors
Bellomo A Celebi-Olcum N Bu X Rivera N Ruck RT Welch CJ Houk KN Dreher SD 《Angewandte Chemie (International ed. in English)》2012,51(28):6912-6915
A microscale chemistry improvement engine: a pre-dosed microscale high-throughput experimentation additives platform enables rapid, serendipitous reaction improvement. This platform allowed one chemist to set up 475 experiments and analyze the results using MISER chromatography in a single day, thus resulting in two high-quality catalytic systems for the construction of the title compound 1. Support for a single-electron transfer mechanism was obtained. 相似文献
11.
Moridi N Elend D Danylyuk O Suwinska K Shahgaldian P 《Langmuir : the ACS journal of surfaces and colloids》2011,27(15):9116-9121
Three amidophenol-modified calixarenes have been produced reacting the parent 5,11,17,23-tetracarboxy-25,26,27,28-tetradodecyloxycalix[4]arene with o-, m-, and p-aminophenol. The produced amphiphiles have been shown to form stable monomolecular Langmuir layers on water. Working on subphases containing 1 mM acetaminophen (APAP), it has been demonstrated that the produced amphiphiles interact with this active pharmaceutically ingredient (API) with a relevant preference for the para-derivative that possesses in its structure substituents that are analogous to the target. Working at supersaturating concentrations of APAP, it has been demonstrated that the so-produced calixarene Langmuir monolayers do favor crystallization of APAP (polymorph I), with a clear effect of the packing density of the amphiphile at the interface on the quantity of produced crystals. Monolayers of the para-derivative have been transferred on solid substrates using the Langmuir-Blodgett technique; the so-produced ultrathin films have been shown to initiate surface crystal nucleation of APAP. The produced solids have been analyzed by single-crystal X-ray crystallography and shown to preferentially grow in the [010] direction. 相似文献
12.
Adsorption characteristics of medicinal carbon powder (JP 14) for acetaminophen were examined at 37 degrees C using conventional incubation in an attempt to obtain an effective oral dosage form. Hydroxypropyl cellulose (HPC) and maltitol (MT), being able to act as a binding agent, were tested as additives. Tablets of medicinal carbon were produced by the wet granulation method. The rate and extent of adsorption of the medicinal carbon powder were roughly similar in water, JP 14 1st fluid (pH 1.2) and JP 14 2nd fluid (pH 6.8). The relationship between concentrations of free and adsorbed acetaminophen indicated that the adsorption followed the Langmuir mode. The maximal adsorption of acetaminophen in water was 0.219 g per gram medicinal carbon powder, little influenced by the addition of MT, but slightly reduced by the addition of HPC. The tablet prepared using MT as a binding agent displayed a favorable hardness and adequate disintegration time. The tablet showed good adsorption potential for acetaminophen, though the adsorption rate and extent of the tablet were reduced to some extent as compared with powder. 相似文献
13.
《Analytical letters》2012,45(13):1003-1012
Abstract A simple electrochemical method for the determination of acetaminophen in serum is described. The eleotrode and associated electronics are simple, reliable, and inexpensive to build. The apparatus can be operated at a rate of 2–3 determinations per minute using only 10 μl serum per determination. The procedure includes extraction of acetaminophen in ethyl acetate and subsequent oxidative amperometric detection of the drug by a form of flow-injection analysis. The system parameters of buffer, pH, and redox potential have been optimized to permit measurement of less than 10 μg/ml of acetaminophen. The determination is linear over the range of 10–300 μg/ml with a C.V. of less than 3% for replicate analysis of the same sample. 相似文献
14.
Rengarajan GT Enke D Steinhart M Beiner M 《Physical chemistry chemical physics : PCCP》2011,13(48):21367-21374
More than 100 years after Ostwald postulated his step rule of stages, predictive understanding as to early crystallization stages of polymorphic materials is still premature. We studied crystallization of the polymorphic pharmaceutical acetaminophen in nanoporous glasses as a model for early stages of bulk crystallization since the surface energy significantly contributes to the total Gibbs free energy of nanosized crystals in both cases. Systematic studies of transitions between different polymorphs inside nanoporous glasses show that the thermodynamic stability of the polymorphs depends on the crystal size. Accordingly, the transient occurrence of different polymorphs during crystal growth in bulk systems can be related to surface energy contributions to the total Gibbs free energy of the developing crystals. In nanosized early-stage crystals with high surface-to-volume ratios other polymorphs may be stable than in large crystals with low surface-to-volume ratios. Improved control of the crystallization of polymorphic materials by imposing well-defined confinement is a promising strategy to tailor release of polymorphic drugs and to optimize optical, electronic, magnetic and ferroelectric properties of polymorphic materials. 相似文献
15.
A M Rustum 《Journal of chromatographic science》1989,27(1):18-22
The determination of acetaminophen in biological samples of humans who have ingested normal and overdosage of the drug is necessary to understand the clinical pharmacokinetics of acetaminophen and to determine its distribution and toxicokinetic parameters. This paper describes a rapid, simple, and sensitive high-performance liquid chromatographic method for determining acetaminophen in human plasma. Acetaminophen is isolated from plasma by adding approximately 200 microL of acetonitrile and 50 mg of solid zinc sulfate to each milliliter of plasma. A short column (60 mm x 4.6 mm) slurry packed with 5.0-microns PRP-1 particles is used with an isocratic elution of 5.0 mM dibasic potassium phosphate and 5.0 mM tetrabutylammonium hydroxide/methanol, 70:30 (v/v). The flow rate is 1.0 mL/min. The acetaminophen peak is detected with a variable wavelength ultraviolet/visible detector at 250 nm and 0.50 to 0.002 AUFS. The analysis time of the assay is less than 15 min, and the limit of detection is 20 ng/mL for an 80-microL injection volume. The pharmacokinetics of acetaminophen in plasma from a subject who had orally ingested 975 mg of the drug in tablet form is conducted using this method, and various pharmacokinetic parameters are determined. 相似文献
16.
A highly efficient method is developed for automated high-throughput screening of nanoliter-scale protein crystallization.
The system integrates liquid dispensing, crystallization and detection. The automated liquid dispensing system handles nanoliters
of protein and various combinations of precipitants in parallel to access diverse regions of the phase diagram. A new detection
scheme, native fluorescence, with complementary visible-light detection is employed for monitoring the progress of crystallization.
This detection mode can distinguish protein crystals from inorganic crystals in a nondestructive manner. A gas-permeable membrane
covering the microwells simplifies evaporation rate control and probes extended conditions in the phase diagram. The system
was successfully demonstrated for the screening of lysozyme crystallization under 81 different conditions. 相似文献
17.
Recent advances in proteomics have provided impetus towards the development of robust technologies for high-throughput studies
of enzymes. The term “catalomics” defines an emerging ‘-omics’ field in which high-throughput studies of enzymes are carried
out by using advanced chemical proteomics approaches. Of the various available methods, microarrays have emerged as a powerful
and versatile platform to accelerate not only the functional annotation but also the substrate and inhibitor specificity (e.g.
substrate and inhibitor fingerprinting, respectively) of enzymes. Herein, we review recent developments in the fabrication
of various types of microarray technologies (protein-, peptide- and small-molecule-based microarrays) and their applications
in high-throughput characterizations of enzymes. 相似文献
18.
The objective of this work was to investigate whether or not the hydrogen bonding interaction between polymer and crystal surface can be detected by the etching pattern changes in the presence of polymers. The (010) face of acetaminophen single crystal was used as a model solid surface. The etching patterns on the (010) face of acetaminophen crystal by water are in the directions of a- and c-axes, which are the same as the directions of the dominant attachment energies on the (010) face. In the presence of polymer, the hydrogen bonding interactions between adsorbed polymer and crystal surface can affect surface diffusion of acetaminophen molecules and change the etching patterns in the direction of a-axis, i.e., the direction of one hydrogen bond chain. Studies with 2-hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) and poly(vinyl alcohol) (PVA) showed that polymers, which can form hydrogen bonds with acetaminophen crystal surface, can change etching patterns in the direction of a-axis. Study with Dextran suggested that if a polymer cannot form hydrogen bonds with crystal surface due to steric repulsion, it will not change the etching pattern in the direction of a-axis. Studies with poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) further confirmed that only if a polymer can form hydrogen bonds with acetaminophen on crystal surface, the etching patterns in the direction of a-axis will be affected. The study results suggest that in the presence of polymers, the etching pattern change in the direction of hydrogen bond chain, the a-axis of acetaminophen crystals, can be used to indicate the existence of the hydrogen bonding interactions between adsorbed polymers and acetaminophen crystal surface. 相似文献
19.
Liang-Bin Li 《高分子科学》2018,(10)
Synchrotron radiation(SR) provides highly brilliant light with tunable wavelength from hard X-ray to far infrared, on which scattering, spectroscopy and imaging techniques with high time and spatial resolutions have been developed for in situ study on biological system and materials like polymer. With examples on flow-induced crystallization of polymer, deformation of nanoparticle filler network in rubber composite and necking propagation in tensile stretch, current work attempts to demonstrate the advantages of in situ synchrotron radiation X-ray scattering, X-ray nano-CT and infrared imaging in the study of deformation-induced multi-scale structural evolutions of polymers. With time resolution up to sub-ms, synchrotron radiation is expected to play a great role in understanding non-equilibrium polymer physics under processing and service conditions, while high-throughput characterization platform based on synchrotron radiation opens the possibility to establish polymer Materials Genome database in processing parameter space within reasonable time, which can serve as the roadmap for industrial polymer processing and accelerate material innovation. 相似文献
20.
Uttamchandani M Liu K Panicker RC Yao SQ 《Chemical communications (Cambridge, England)》2007,(15):1518-1520
A panel of 20 peptide vinyl sulfone probes has been synthesized and used to generate activity-based fingerprinting profiles of cysteine proteases in both gel- and microarray-based formats; the inhibitor fingerprints of representative small molecule inhibitors targeted against 4 cysteine proteases were also obtained, in high-throughput, using the same protein microarray platform. 相似文献