WO2001034660A2

WO2001034660A2 - Screening and analysis of polymers, specialty chemicals and catalysts using radiography

Info

Publication number: WO2001034660A2
Application number: PCT/US2000/030720
Authority: WO
Inventors: Christopher D. Tagge; Robert B. Wilson; Seajin Oh
Original assignee: Sri International
Priority date: 1999-11-09
Filing date: 2000-11-09
Publication date: 2001-05-17
Also published as: WO2001034660A3; AU1476501A

Abstract

The invention relates to methods, using radiography, for the analysis of chemical compounds, such as polymers, specialty chemicals, and catalysts. In particular, the methods of the invention provide methods, which may be carried out in a highly parallel manner, for the synthesis and analysis of chemical compounds in a high-throughput or combinatorial manner. According to the invention, a substrate having a plurality of reaction regions is employed. Next, polymerization, synthesis or adsorption steps are carried out with one or more radiolabeled reagents. The radioactivity in the resulting product provides a measure of various physical properties. For instance, the methods of the invention may be used to determine the comonomer content of polymers, the productivity of catalysts, and/or the incorporation of a reagent in a specialty chemical. In addition, the invention provides means for determining a variety of chemical and physical properties of porous catalysts, including surface area, the number of active sites, the number of acidic or basic sites, pore size distribution, and chemisorption.

Description

Screening and Analysis of Polymers, Specialty Chemicals and Catalysts Using Radiography

This application claims benefit under 35 U.S.C. §119 to U.S. Provisional Application Nos. 60/164,342 filed November 9, 1999, 60/167,227 filed November 24, 1999; and 60/224,411 filed August 10, 2000; the disclosure of these three applications is hereby incorporated in their entirety by reference.

Field of Invention The invention relates to methods, using radiography, for the analysis of polymers, specialty chemicals, and catalysts. The invention also relates to combinatorial and high- throughput techniques for the synthesis and characterization of polymers, specialty chemicals, and catalysts using radiography.

Background The use of combinatorial techniques to generate libraries of chemical and/or biological compounds is known in the art. Once a library has been generated, it is usually necessary to screen the compounds or mixtures to determine if the desired properties are present. However, most techniques developed for screening and characterization of combinatorial libraries are sequential, involve sample preparation or sample transfer steps, and are generally labor-intensive, time-consuming and expensive for large libraries or arrays of several compounds. For example, comonomer content of a polymer is conventionally measured through time intensive techniques such as NMR spectroscopy; however, such methods are ineffective for the analysis of large numbers of compounds.

Thus, methods for the characterization of large numbers of compounds, in an efficient and highly parallel manner are needed in the art.

Although radiography has been used for screening biological samples, radiography has not been applied to combinatorial or high-throughput techniques for the characterization of chemical products. WO 97/37953 describes mass-based encoding and qualitative analysis of combinatorial libraries; however, the focus is on inserting an isotopically labeled tag into solid state combinatorial synthesis constructs, followed by mass spectrometry, mass-based nuclear magnetic resonance spectrometry or mass-based infrared spectrometry analysis as a means for physical, non-chemical encoding of large numbers of combinatorial synthesis products. These techniques are not adapted to the analysis of the chemical and physical properties of the products that are synthesized in arrays and combinatorial libraries. Radiolabels have been used as tracers and tags. For instance, reactivity ratios were studied in the co-polymerization of methyl methacrylate with chlorine-36 vinyl chloride, as described in McNeill, I.C. and Straiton, T '.; European Polymer Journal, 13(1):17-18 (1977). Certain physical and chemical properties of catalysts have been studied using various radioisotopes as labels. For example, radioisotopes have been used as tracers for the study of physical and chemical properties of nickel/silica catalysts in Jackson, S.D., et al., Catalysis Today, 10(3):323-328 (1991). The exchange process of preadsorbed ¹⁴CO on Pd/Al₂O₃ is reported in Schroder, TJ. and Schδδn, N.-H.; Journal of Catalysis; 143:381-387 (1993). The chemisorption of ¹⁴C-labeled benzene on nickel, platinum, and copper catalyst has been investigated; see Tetenyi, P. and Babernics, L.; Journal of Catalysis, 8:215-222 (1967). In addition, studies of the adsorption of ¹⁴C-labeled acetylene, ethylene and carbon monoxide with rhodium supported on silica or alumina catalysts, is described in Reid, J.U., Thomson, ST., and Webb, G.; Journal of Catalysis; 30:372-377, 378-386 (1973).

Radiolabels have also been used to investigate the number of active centers in Ziegler-Natta catalysts. For example, the number of active centers of a Ziegler-Natta catalyst has been determined using inhibition and kinetic studies employing a radioisotope; see Abu-Eid, M, Davies, S. and Tait, P.J.T.; Polymer. Prep. 24(1): 114-115 (1983). The determination of the number of active centers of various Ziegler-type catalyst systems, using ¹⁴CO radiolabels has been reported in Jaber, LA. and Fink, G.; Makromol. Chem., 190:2427-2436 (1989); Jaber, LA., Hauschild, K., and Fink, G.; Makromol. Chem., 191 :2067-2076 (1990); and Marques, M.M., Tait, P.J.T., Mejzlik, J., and Dias, A.R.; Journal of Polymer Science: Part A: Polymer Chemistry, 36:573-585 (1998).

Cracks and formations in polymer films have been investigated by diffusing a radiolabeled gas or liquid into a preformed polymer and scanning the sample using radiography. See e.g., Figge, K. et al, Deut. lebensm-Rundsch 66(9):281-9 (1970), Bellazzini, R et al, Nucl. Instrum. Methods Phys. Res. Sect. A A251(1): 196-8 (1986), Mysak, F. et al, Izotoptechnika, 14(l-2):27-28 (1971), Bekman, I. N., et al. Radiokhimiya 28(2):222-229 (1986), and Kocbynka, D. et al, Radioisotopy 8(6):860-l (1967).

Despite the use of radioisotopes in certain assays and studies, as described above, radiography has generally not been adapted or extended to the characterization of an array of chemical compounds, such as polymers, catalysts or specialty chemicals, in a high- throughput manner. Sequential techniques involve time-consuming and inefficient methods for the analysis of large libraries or arrays of chemical compounds. There are also few empirical rules available to predict the properties of a final product, based on the catalyst composition or structure. Therefore, combinatorial or high-throughput techniques for the screening and characterization of large collections of chemical compounds, including polymers, specialty chemicals and catalysts are needed in the art. Such methods preferably provide a qualitative and/or quantitative determination of properties such as comonomer content, amount of incorporation of a reagent into a final product, and/or various properties of catalysts. This invention answers this need.

Summary

The invention relates to methods, using radiography, for the analysis of chemical compounds. In particular, the methods of the invention provide analytical methods, which may be carried out in a highly parallel manner, and which are useful in the synthesis and analysis of chemical compounds in a high-throughput or combinatorial manner. In a preferred embodiment, these methods may be used to analyze a variety of polymers, specialty chemicals, and catalysts.

In a first embodiment, the invention relates to a method for the synthesis and analysis of polymers. This method involves providing a substrate having a plurality of reaction regions, and delivering a monomer or mixture of monomers to two or more reaction regions. At least one of the monomers is a radiolabeled monomer. Next, the monomer or mixture of monomers is polymerized. After the polymerization step, any unreacted radiolabeled monomer may be removed from the reaction region. The radioactivity of the polymer in the reactor regions is then measured. The radioactivity provides a means for determining the yield of the polymerization reaction in the reaction region. Further, in cases where a copolymer is formed, the copolymer content may be determined, e.g. the ratio of a first radiolabeled comonomer with respect to a second comonomer that contains a different radiolabel, or the ratio of first comonomer with respect to the mass of polymer produced. Moreover, in another embodiment of the invention, where known amounts of different catalysts are delivered to the reaction regions prior to the polymerization step, the invention provides a method for determining the productivity of the catalysts, either in parallel or sequentially. The productivity of a catalyst during the polymerization may be monitored by measuring the heat produced during the reaction, for instance, using calorimetry or thermography. According to the invention, the productivity of the catalyst may also be determined from the same polymerization, based on the radioactivity of the resulting polymer.

In another embodiment of the invention, the amount of incorporation of a reagent into a specialty chemical is measured using radiography. In a method for the synthesis and analysis of a fine chemical, a substrate having a plurality of reaction regions is provided. The method involves delivering a reagent or mixture of reagents, where at least one reagent is a radiolabeled reagent. Optionally, a catalyst, co-catalyst, activator, or reaction solvent may also be added to the reaction regions. The reaction may be conducted either in parallel or sequentially. After the reaction step, any unreacted radiolabeled reagent may optionally be removed from the reaction regions. The radioactivity of the products is measured, either during the reaction or after the reaction. This embodiment provides a method for determining the conversion of the reactants. Also, according to the invention, it is possible to determine the amount of radiolabeled reagent incorporated in the product. Moreover, in another embodiment, a catalyst may be provided to the reaction region, and the productivity of the catalyst may be determined. For example, the catalyst productivity may be determined by monitoring the heat emitted or absorbed during the reaction, e.g. using calorimetry or thermography, or by determining the radioactivity of the resulting chemical compound and correlating the radioactivity to the productivity of the catalyst.

Also according to the invention is a method for the analysis of chemical and physical properties of porous catalysts. A substrate having a plurality of reaction regions is provided, and then a porous catalyst is provided to two or more reaction regions. A radiolabeled compound is provided to the reaction regions under conditions sufficient for the radiolabeled compound to be adsorbed by the porous catalyst. Finally, the radioactivity of the catalyst after adsorption of the radiolabeled porous catalyst is measured. The radioactivity may be correlated to the surface area, the number of active sites of a porous catalyst, and/or the number of acidic or basic sites of a porous catalyst.

The invention also relates to a method for analysis of the pore size distribution of porous catalysts, comprising the steps of first providing a porous catalyst to a reaction region on a substrate, as described above. A mixture of radiolabeled compounds is provided to the reaction regions under conditions sufficient for the radiolabeled compound to be adsorbed by the porous catalyst. The mixture of radiolabeled compounds comprises compounds having different molecular sizes, where compounds of different molecular sizes are uniquely labeled with different radiolabels. By measuring the relative amounts of each radiolabel incorporated into the catalyst after adsorption of the mixture of radiolabeled compounds, it is possible to determine the pore size distribution.

According to the invention, a method for measuring, either in parallel or sequentially, the exchange rate between different adsorbed species for a porous catalyst is provided. The exchange rate is the rate of displacement of a first adsorbed species by a second adsorbed species from the porous catalyst, as monitored over time. According to the invention, in a first step, an array comprising a plurality of reaction regions is provided. A porous catalyst is provided to two or more reaction regions, wherein the porous catalyst has a first adsorbed species, which is radiolabeled. Then a second radiolabeled adsorbed species is provided to the reaction regions. By measuring the exchange rate of the first radiolabeled adsorbed species for the second radiolabeled adsorbed species, the exchange rate of different adsorbed species can be determined.

Any of the embodiments of the invention may be used either alone or taken in various combinations. Additional objects and advantages of the invention are discussed in the detailed description that follows, and will be obvious from that description, or may be learned by practice of the invention. It is to be understood that both this summary and the following detailed description are exemplary and explanatory only and are not intended to restrict the invention.

Detailed Description In general, the invention relates to various methods, using radiography, for the analysis and characterization of chemical compounds, such as polymers, specialty chemicals, and porous catalysts. While any equipment or apparatus designed for high- throughput or combinatorial chemistry may be used, the methods of the invention employ a substrate having a plurality (i.e. two or more) of reaction regions.

According to the invention, a substrate having a plurality of reaction regions is employed. Next, polymerization, synthesis or adsorption steps are carried out with one or more radiolabeled reagents, or with radiolabeled starting materials. The amount of the radiolabeled reagent or starting material incorporated into the resulting chemical product may be monitored using radiography. In cases where the starting material is radiolabeled, it is also possible to monitor the loss of radioactivity, i.e. in a decomposition reaction. In either case, the change in the radioactivity is measured or monitored over time using radiography. The amount of radioactivity in the resulting product may then be used to determine various physical and chemical properties. For instance, the methods of the invention are used to determine the comonomer content of polymers, the productivity of catalysts and/or the incorporation of a reagent in a specialty chemical. In addition, the invention provides means for determining a variety of properties of porous catalysts, including surface area, the number of active sites, the number of acidic or basic sites, pore size distribution, and chemisorption.

The Substrate

The substrate used in the invention may be any material having a rigid or semi-rigid surface, and may be in any shape that is convenient and practical, e.g. an array comprising several wells, a spot plate, or a test tube rack. The substrate may be fabricated from any material which is compatible with the reaction conditions and reagents to be used. The substrate typically comprises one or more materials selected from silicon, doped silicon, silicon dioxide, doped silicon dioxide, steel, sapphire, glass materials, ceramic materials, plastic materials, and mixtures thereof. Acceptable materials for the substrate include a variety of materials, including but not limited to: Pyrex, quartz, resins, carbon, metals, or inorganic crystals. In particular, suitable materials for the array include steel and steel alloys, including materials such as stainless steel. A variety of ceramic materials, such as silicon nitride, silicon oxynitride, aluminum nitride, boron nitride, aluminum oxide, zirconium oxide, silicon carbide, lithium aluminum silicate and mixtures thereof may also be used. Several plastic materials are also well suited for the fabrication of the array. Typical plastic materials comprise at least one of polyethylene, polypropylene, polystyrene, polycarbonates, polyimides, poly(vinyl chloride), fluorinated polymers (for example, such as tetrafluoroethylene fluorocarbon polymers and fluorinated ethylene- propylene resins), acrylic, and poly(ethylene terephthalate). The substrate may be a hybrid substrate, with different sections made from different materials. For instance, it may be desirable to bond together a glass plate having wells and channels machined and/or etched therein, with a silicon wafer that forms the bottom of the wells. Other suitable materials are known in the art.

When the array is made from a silicon wafer, the array has the additional feature and advantage of being well adapted for single-use applications. In particular, the array may be disposable or archivable. By batch-fabricating the array, the array may be produced at a cost such that it is cost-effective to dispose of the array after use, which avoids time-consuming cleaning operations and the risk of contamination. Alternatively, the array may be archived for future studies or characterization.

The reaction regions on the substrate may be in the form of wells, dimples, or raised regions, which permit reactions to occur in separate areas or compartments. There may be a physical barrier between the reaction regions, or the reactions may be conducted in physically separate compartments or containers, and assembled together into a substrate or an array, i.e. a test tube rack, or an array made up of individual blocks or containers each having reaction regions.

In general, the reaction regions may be of any size and volume that is practical. In a preferred embodiment, the reactions may be run on small scale or microscale. Advantages of the microscale include smaller reactor volume, lower costs for reagents and labor, generally higher throughput, and compatibility with commercially available radiographs. The reaction regions may have a volume of less than about 1 μL. In particular, the array may comprise wells having a volume of from about lnL to about 500 μL, from about 0.1 μL to about 100 μL, or from about 0.25μL to about 10 μL.

In a preferred embodiment, the substrate is an array, such as described in co- pending U.S. Provisional Application Nos. 60/164,342 filed November 9, 1999 and 60/167,227 filed November 24, 1999, as well as U.S. Application "Array for the High- Throughput Synthesis, Screening, and Characterization of Combinatorial Libraries" and "Workstation, Apparatus, and Methods for the High-Throughput Synthesis, Screening, and Characterization of Combinatorial Libraries" both filed on November 9, 2000; the disclosure of all these applications is hereby incorporated in their entirety by reference. The array, as described in these applications, contains wells (typically used as reaction regions), and/or thermal channels which may be used to regulate or monitor the temperature of the reactions in the reaction regions. The wells and thermal channels may be in the form of dimples, wells, raised regions or etched trenches in the substrate.

Typically substrates have a plurality (i.e. two or more) reaction regions, and may have rows and columns in arrangements of about 8 x 12, and multiples thereof (i.e. 16 x 24, 32 x 48, etc.), or arrays of about 10 x 10, and multiples thereof (i.e. 100 x 100, 1000 x 1000, etc.). The number and arrangement of the reaction regions depends upon the particular application involved, and are known or easily determined by one of ordinary skill in the art. In another preferred embodiment, the substrate may be part of an apparatus optionally comprising an array cover, an array, a reaction stage, and/or means for attaching the array cover, the array, and the reaction stage. The array cover may comprise one or more gas manifolds. For instance, there may be one gas manifold, common to all of the wells. Alternatively, there may be several gas manifolds corresponding to specific rows or columns. In another embodiment, the array cover may have an array of gas manifolds, disposed over each of the individual reaction regions. The gas manifolds may be used to introduce a gaseous reagent or other gas into the wells of the array, provide an inert atmosphere, remove gaseous side-products from the wells and/or provide a vacuum to the wells.

In general, the apparatus may further comprise means for controlling the temperature of the wells. Such means may be incorporated into any combination of the array cover, the array, or the stage. For example, some reactions or processes require heat, and in such instances, the reaction stage may comprise means for heating, such as individual thermocouples or a heating block. Alternatively, the array may further comprise one or more thermal channels, or an array of thermal channels, which are used to regulate the temperature inside the wells.

The thermal channels may be metalized for resistive heating, or doped with a material selected from the group consisting of boron, phosphorus, or arsenic, among others. In other embodiments of the invention, the thermal channels may contain a fluid or gas, which is used to regulate the temperature. Preferably, the thermal channels contain a coolant, such as nitrogen, air, water, methanol, hydrocarbons, or halogenated hydrocarbons, which permits the reactions within the wells to be run at a desired temperature. Thus, according to the invention, the reactions within each well can run under isothermal conditions. In addition, the thermal channels allow for the study of different reaction temperatures in different reaction regions of the same substrate. In preferred embodiments, the thermal channels may be aligned parallel to at least one row or column, or may define a checkerboard pattern around the wells of the array.

In a preferred embodiment, the array can be easily interchanged between different stations or analytical instruments without requiring transfer of compounds or components of the library from the array. This feature of the array reduces sample preparation and sample transfer steps. Starting Materials

As described previously, in one embodiment, the invention comprises methods for the analysis and/or synthesis of polymers and catalysts. According to the invention, a polymerization reaction is carried out by delivering a monomer or mixture of monomers to reaction regions on a substrate. Optionally, solvent, one or more catalysts, co-catalysts, activators, etc. may be delivered to the reaction regions as well. The monomer or mixture of monomers is selected from any commercially or synthetically available monomer starting material. As discussed below, at least one of the monomers contains a radiolabel.

Monomers containing radiolabels may be either commercially available, or synthetically produced from commercially available reagents and/or starting materials containing a radiolabel. As an example, but not a limitation, the monomer or mixture of monomers used in the invention are typically selected from a variety of linear olefins, branched olefins, cyclic olefins, diolefins, and aromatic olefins. Examples of these include, but are not limited to: ethylene, propylene, cis-2-butene, butadiene, 1-hexene, 1- octene, 1-butene, 3 -methyl- 1-butene, 1,3-butadiene, 1-pentene, 4-methyl-l-pentene, 1- hexene, 4-methyl- 1-hexene, 1,4-hexadiene, 1,5-hexadiene, 1-octene, 1,6-octadiene, 1- nonene, 1-decene, 1 ,4-dodecadiene, 1-hexadecene, 1-octadecene, cyclopentene, 3- vinylcyclohexene, 5-vinyl-2-norbornene, 5-ethylidene-2-norbornene, dicyclopentadiene, 4- vinylbenzocyclobutane, tetracyclododecene, dimethano-octahydronaphthalene, 7-octenyl- 9-borabicyclo-(3,3,l)nonane, styrene, o-methylstyrene, /w-methylstyrene,/?-methylstyrene, ?-tert-butylstyrene, w-chlorostyrene, ?-chlorostyrene,

indene, 4- vinylbiphenyl, acenaphthalene, vinylfluorene, vinylanthracene, vinylphenanthrene, vinylpyrene, vinylchrisene, methylmethacrylate, ethylacrylate, vinyl silane, phenyl silane, trimethylallyl silane, acrylonitrile, maleimide, vinyl chloride, vinylidene chloride, tetrafluoroethylene, isoprene, isobutylene, carbon monoxide, acrylic acid, 2- ethylhexylacrylate, methyl acrylate, methyl methacrylate, methacrylonitrile, methacrylic acid, vinyl acetate, norbornene, norbornadiene, and mixtures thereof.

In another embodiment, the invention relates to methods for determining the amount of incorporation of a reagent into a specialty chemical, i.e. a fine chemical, or a performance chemical. A fine chemical is a pure, single substance produced by a chemical reaction. Fine chemicals encompass a broad category of chemicals, including but not limited to: basic building blocks, advanced intermediates, pharmaceuticals, standard bulk compounds, cosmetic ingredients, food additives, household chemicals, agricultural products, pesticides, analytical chemicals, dyes and stains, and photographic chemicals, for example. Performance chemicals are typically mixtures of substances, proprietary products, and formulated with carriers or solvent. See Stinson, S.C., ''Pharmaceutical Fine Chemicals", Chemical &Engineering News, 78(28):63-80 (2000). As used in the invention, the term specialty chemical does not include large biomolecules, i.e. polynucleotides. However, pharmaceuticals including small molecule peptides are considered specialty chemicals.

According to the invention, specialty chemicals, fine chemicals and performance chemicals can also be synthesized and then analyzed using radiography. Although commercially available fine chemicals are usually sold in a pure form as a single compound, for the purposes of this invention, it is permissible to perform analysis of the fine chemical, although there may be solvent, side products, or other compounds in the reaction region. Thus, the fine chemical does not necessarily have to be purified prior to the analysis step.

The invention comprises providing a substrate having a plurality of reaction regions, as described above. A first reagent, and a second reagent are delivered to a reaction region, where at least one of the first reagent or second reagent is a radiolabeled reagent. Optionally, solvents, one or more catalysts, co-catalysts, activators, etc. may be added. The reagents may be selected from any commercially available and/or synthetically available reagents. Appropriate reagents and reaction conditions are known to one of ordinary skill in the art, or may be determined by routine experimentation. For instance, see March, J ^'., Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Fourth Edition, Wiley-Interscience, John Wiley & Sons, New York, New York (1992); Hassner, A., and Stumer, C, Organic Synthesis Based on Name Reactions and Unnamed Reactions, Pergamon, Tarrytown, New York (1994); and Mundy, B., and Ellerd, M.G.; Name Reactions and Reagents in Organic Synthesis, John Wiley & Sons, New York, New York (1988).

Radiolabels

As described above, the invention uses various radiolabeled reagents and monomers. According to the invention, a radiolabel is an isotope which is radioactve. A radioactive isotope will undergo nuclear transformation, emitting energy in the form of , β, or γ rays. Radioactivity is generally not affected by the physical state, temperature, pressure, or chemical combination of the element. The radioactivity of a nuclide is characterized by the nature of the radiation, the energy, and the half-life of the process, i.e. the time required for the activity to decrease to one half of the original. Half-lives vary from microseconds to millions of years. To be effectively used as a radiolabel, the radioisotope must display a half-life appropriate to the particular process being used. For instance, the half-life must usually be long enough to complete the polymerization, reaction or adsorption steps, and the analysis steps. Suitable radiolabels can be selected depending on the particular reaction or polymerization to be studied. Information regarding the half-lives of radioisotopes, modes of decay, decay energies, etc. may be found in various handbooks; see Robert C. Weast, Editor, CRC Handbook of Chemistry and Physics, 64th Edition, CRC Press, Boca Raton, Florida (1983), which is hereby incorporated in its entirety.

Typical radioisotopes which may be used as the radiolabel include, but are not limited to, ³H, ¹⁴C, ¹²⁵1, ⁸⁵Kr, ²²²Rn, ¹²⁵1, ³³P, ³²P, ³⁵S, ³⁶C1, and combinations of these. In a preferred embodiment, the radioisotope used as the radiolabel is ³H and/or ¹⁴C, which have half-lives of about 12.26 years and 5730 years respectively.

In additional to commercially available reagents and starting materials, it is also possible to synthesize radiolabeled compounds, using commercially available starting materials and reagents. Standard organic chemistry techniques may be used to synthesize a variety of radiolabeled reagents from commercially available starting materials and reagents.

For instance, radiolabeled comonomers may be prepared from commercially available isotopically enriched alcohols, as shown in the following scheme, where the radiolabeled carbon is indicated by the asterisk (*):

H₂SO,,, 180°C

catalyst

Other synthetic methods for incorporating radioisotopes into starting materials and reagents are known in the art. The synthetic methods used are analogous to standard synthetic organic techniques, and are known to one of ordinary skill in the art.

Catalysts

Optionally, one or more catalysts are delivered to the reaction regions prior to the reaction step. The catalyst may be any chemical compound that accelerates or initiates chemical reactions. Typical catalysts may be inorganic, organic, or a complex of organic groups and metal halides. The catalyst may be selected from a wide variety of catalysts including, but not limited to: acids, bases, mixed metal oxides, mixed metal nitrides, mixed metal sulfides, mixed metal carbides, mixed metal fluorides, mixed metal silicates, mixed metal aluminates, mixed metal phosphates, noble metals, zeolites, metal alloys, intermetallic compounds, inorganic mixtures, inorganic compounds, inorganic salts, radical catalysts, cationic catalysts, anionic catalysts, anionic coordination catalysts, and mixtures thereof. See Richard J. Lewis, Sr., Hawley's Condensed Chemical Dictionary, Thirteenth

Edition, John Wiley & Sons, Inc., New York, 1997. Typical catalysts, which may be used in the invention, include but are not limited to: Ziegler-Natta catalysts, metallocene catalysts, stereospecific catalysts, constrained geometry catalysts, single-site catalysts, late transition metal single-site catalysts, free radial initiators, living free radical initiators, cationic initiators, anionic initiators, co-ordination complexes and mixtures thereof.

In a preferred embodiment, the catalysts are supported catalysts. In general, the solid support material may include any material known to one of ordinary skill in the art.

Typical supported catalysts, and methods of making and using precipitated catalyst supports in polymerization processes are known to those of ordinary skill in the art, and are described, for example, in U. S. Patent Nos. 5,747,407; 5,206,314; 5,081,090; 4,946,816;

4,831,091; and 4,567,155, and WO 92/13009, as well as George M. Benedikt and Brian L.

Goodall, Eds., Metallocene-Catalyzed Polymers: Materials, Properties, Processing &

Markets, Plastics Design Library, (1996); George M. Benedikt and Brian L. Goodall, Eds.,

Metallocene Technology: in Commercial Applications, Plastic Design Library, William

Andrew Inc. (1999); Fink, G.; Muelhaupt, R.; Brintzinger, H.H.; Editors; Ziegler

Catalysis, Springer, Berlin, Germany, (1995); Peter Roos et al., Macromol. Rapid

Commun., 18:319-324 (1997); and Elodie Bourgeat-Lamie and Jacques Lang, Journal of

Colloid and Interface Science, 197:293-308 (1998) which are all hereby incorporated by reference. Typical solid support materials include, but are not limited to: porous resinous materials selected from the group consisting of copolymers of styrene-divinylbenzene, or solid inorganic oxides, selected from the group consisting of silica, alumina, magnesium oxide, magnesium chloride, titanium oxide, thorium oxide, mixed oxides of silica and one or more Group 2 or 13 metal oxides. In a preferred embodiment, the solid support material is selected from the group consisting of silica-magnesia and silica-alumina mixed oxides, or from the group consisting of silica, alumina, and mixed oxides of silica and one or more Group 2 or 13 metal oxides.

Analysis of Catalysts

The invention also provides methods for analysis of the catalysts in the polymerization and synthesis reactions. For instance, the productivity and/or activity of the catalyst may be also measured. The productivity of the catalyst is the polymer or product per unit of catalyst. Activity is polymer per unit of active catalyst sites. The invention provides a convenient means for determining the productivity and/or activity of catalysts. The catalysts may be analyzed based on the heat produced during the reaction, i.e. monitoring the reaction using calorimetry or thermography. The catalysts may also be studied, based on the amount of heat absorbed during the reaction; for a discussion of IR- thermographic screening of thermoneutral or endothermic transformations, see Reetz, M. T. et al., Angew. Chem. Int. Ed. 39(7): 1236-1239 (2000).

The activity and productivity of the catalysts may also be determined by the radioactivity of the final product. For example, in a homopolymer produced from a radiolabeled monomer, the radioactivity is directly correlated to the activity of the catalyst.

The invention may be used to study whether different catalysts incorporate different ratios of reagents or starting materials. In this case, for specialty chemicals, different ratios of reagents may be incorporated in the final product. In polymer chemistry, each catalyst may incorporate different proportions of monomer or comonomer in the resulting polymer. In this embodiment, the total amount of the specialty chemical or polymer product is determined, and the amount of radioactivity is measured. By measuring the radioactivity of the product, it is possible to determine the relative amount of radiolabeled reagent that is incorporated into a specialty chemical, or in the case of polymerization reactions, it is possible to determine co-monomer content. In an embodiment of the invention, by using two or more different radiolabeled monomers or reagents, it is also possible to determine co-monomer content in a copolymer, or the ratio of reagents incorporated in a specialty chemical. In this embodiment, different reagents or monomers comprise a different radiolabel. By measuring the radioactivity corresponding to each radiolabel, it is possible to determine the relative amounts of each corresponding monomer or reagent in the resulting product, i.e. the polymer or specialty chemical.

Polymerization, Specialty Chemical Reactions, and Processing Steps

The reagent or monomer, including the radiolabeled reagent or monomer, may be delivered to the reaction regions by any means known in the art. In addition, any catalyst, co-catalyst, activator, solvent, etc. as required, may be delivered to each of the reaction regions, either manually or through an automated system. Typical delivery systems include pipette and other dispensers. Alternatively, the reagent may be delivered by one or more gas manifolds, positioned over the reaction regions.

Polymerization

For polymer studies, after the delivery step, the monomer or mixture of monomers, are polymerized under conditions sufficient to form a polymer. The polymerization step may be carried out under suitable reaction conditions, as known to one of ordinary skill in the art, e.g. a gas phase polymerization, a slurry phase polymerization, solution polymerization, or an emulsion polymerization. The polymerization reaction may typically require initiators, activators, heat and/or light. According to the invention, the polymerization reaction may be run under high pressure. The polymerization reaction may be carried out (1) in the gas phase, typically at high pressures and temperatures of greater than 50°C, (2) in solution at normal to high pressure and at normal to high temperatures, typically from about 0°C to about 70°C, (3) in slurry, typically at normal to high pressures, and at temperatures ranging from about 50°C to over 200°C, or (4) in emulsion form, typically at normal pressures, and at temperatures from about -20 to about 60°C. See Richard J. Lewis, Sr., Hawley's Condensed Chemical Dictionary, Thirteenth Edition, John Wiley & Sons, Inc., New York, New York, 1997 and Odian, G., Principles of Polymerization, Third Edition, John Wiley & Sons, Inc., New York, New York, 1991, for a general discussion of polymerization techniques. In an embodiment of the invention, the polymerization step in each reaction region may be carried out either in parallel, or sequentially. After the reaction step, the polymers produced may be transferred to a second array for analysis, or in a preferred embodiment, the array that was used for the polymerization step is also used for the analysis step, described below.

In addition to polymerization reactions, the invention also applies to an embodiment for the synthesis and analysis of specialty chemicals. In this embodiment, the first and second reagents, and optionally any catalysts, cocatalysts, activators, solvent, etc. as required, are exposed to conditions sufficient to form a product. Suitable reaction conditions depend upon the reaction, and are apparent to one of ordinary skill in the art. The reaction steps may be carried out either in parallel or sequentially.

Specialty Chemical Reactions

According to the invention, the specialty chemicals may be made by a variety of reactions known in the art, whereby at least one radiolabeled reagent is monitored, either by incorporation into a product, or by disappearance from a starting material. Typical reactions include, but are not limited to the following: condensation, decomposition, oxidation, reduction, combination, replacement, hydrolysis, hydrogenation, hydro silylation, hydrocyanation, hydroformylation, carbonylation, metathesis, cross coupling, hydration, dimerization, enolization, saponification, covalent interactions, ligand binding, hydroboration, hydrohalogenation, and combinations of these. Examples of addition reactions include hydrogenation, hydroboration, hydrohalogenation, hydroxylation, hydroformylation, halohydrination, alkylation, carbene addition, dihalo carbene addition, carbonylation, epoxidation, aziridination, and combinations of these. Preferred reactions include catalytic hydrogenation, carbonylation, hydroformylation, epoxidation, and aziridination, as examples. This list is not meant to be exclusive. One of ordinary skill in the art can apply the methods of this invention to other suitable reactions.

Processing Steps

The reactions may be conducted using any combinatorial and high-throughput processes known in the art. The synthesis may create mixtures of compounds, or arrays of individual compounds in each reaction region of the substrate. In cases where mixtures of compounds are synthesized, screened and/or characterized, there is often also a method of identifying compounds of interest. These methods may be either spatial, (such as through spatially addressable synthesis or chemical encoding), or systematic, (such as through a series of deconvolutions). Spatially addressable synthesis refers to the generation of an array of compounds where each reaction well comprises an individual reaction product or compound. Chemical encoding may take the form of a number of inert chemical tags to identify each compound. Iterative deconvolution involves the identification of the most active mixture, followed by fixing some specific part of the molecule and making a smaller library; this process is repeated until a single compound is identified. Other deconvolution, positional scanning, and encoding methods are known in the art. See Wilson, S.R. and Czarnik, A. W., Eds., Combinatorial Chemistry, John Wiley & Sons, New York, 1997, which is hereby incorporated in its entirety.

After the polymerization or reaction steps, it may be necessary to remove any unreacted or excess radiolabeled reagents, in order to accurately measure the radioactivity and/or mass of the resulting product, i.e. the polymer or the specialty chemical. The excess radiolabeled reagent may be removed by any means known in the art, including applying a vacuum, or by flushing the reaction regions with an inert fluid (such as argon or helium gas) or using a solvent, until no radioactivity is detected in the exit gas or wash solution. Optionally, any volatile solvents, and unreacted starting materials or reagents, may also be removed.

It is to be understood that the invention may also be practiced without necessarily having to remove excess radiolabeled compounds. For instance, it is possible to provide a constant feed of the radiolabeled compound at a constant pressure during the reaction, polymerization or adsorption step, which provides a constant level of background radioactivity. As the radioactivity is incorporated into the product in the reaction region, it is then possible to monitor, over time, the amount of radioactivity that is incorporated into the polymer, specialty chemical, or porous catalyst. Using this method, it is possible to monitor either an increase or decrease in the amount of radioactivity in the reaction regions over time.

In a preferred embodiment, the same array is used for both the synthesis and analysis steps, since this avoids time-consuming and possibly expensive transfer and handling steps. However, in another embodiment of the invention, it may be desirable to purify and/or isolate a product prior to the analysis step. It may be possible to conduct any purification, isolation, or separation steps directly in the reaction regions. For instance, certain volatile side products or solvents can be removed from the reaction regions using reduced pressure. However, in an embodiment of the invention, it is also possible to separate the resulting products, and transfer them to a second substrate also having a plurality of reaction regions, for carrying out the analysis steps.

Automation of Process

In an embodiment of the invention, one or more steps are automated. For instance, the invention may be carried out in a workstation, where one or more of the materials, i.e. starting materials, catalysts, co-catalysts, activators, solvents, reagents, etc., is delivered using an automated system. For example, a number of pipetters and robotically or computer controlled workstations are known in the art. Such systems may be also programmed to dispense specified quantities of compounds into certain reaction regions at certain times, over the course of the reaction. In addition, it is also possible to use an automated system to regulate or program the temperature(s) or pressure(s) in the reaction regions.

The analysis of the products may also be carried out using an automated system. In an embodiment of the invention, the entire substrate may be transferred between a number of workstations, each designed for a different type of analysis technique. This embodiment provides a method for characterizing many different properties of the products, in an efficient manner that does not involve sample handling or transfer steps. Such a workstation has been described in co-pending U.S. Provisional Application No. 60/167,227 filed November 24, 1999; the disclosure of which is hereby incorporated by reference.

Analysis of Products

After the reaction is complete, the compounds may be analyzed for radioactivity.

As known in the art, a variety of methods may be used to detect emissions from radioactive substances. For example, photographic plates and film may be used. The photographic film or plate can provide a quantitative measure of activity. The greater the extent of exposure to radiation, the darker the area of the developed negative. Radioactivity can also be detected and measured using a Geiger counter, where the ions and electrons produced by the ionizing radiation permit conduction of an electrical current, which can be correlated to the amount of radiation produced. A scintillation counter may be used to detect and measure fluorescence caused by radiation, and thereby the radiation that causes it. In a preferred embodiment of the invention, radioactivity is measured using an autoradiograph. Digital autoradiography equipment is commercially available. Typical autoradiographs which are used in this invention include those commercially available from sources such as EG&G Berthold, Gaithersburg, Maryland. Typical models used include, but are not limited to the LB 287 Digital autoradiograph, and LB 285 and LB 284 Linear Analyzers. Some recent advances are described in Lees, J. E., Fraser, G. W., Carthew, P., Nucl. Instr. Meth. A., 40 (1998). The step of measuring the radioactivity of the product may be performed in parallel or sequentially, and/or may be automated.

When a catalyst is used, the radioactivity provides a measure of the productivity and/or activity of the catalyst. The productivity of the catalyst is the polymer or product per unit of catalyst. Activity is polymer per unit of active catalyst sites. The total radioactivity of the final product can provide a measure of the total amount of polymer or specialty chemical produced, i.e. the yield of the reaction. In an embodiment where the amount of catalyst in each reaction region is the known, the radioactivity can then also be correlated to the productivity of the catalyst.

In another embodiment, the productivity of the catalyst activity or productivity may be monitored during the course of the reaction by measuring the amount of heat emitted or absorbed, e.g. using thermography or calorimetry. The catalyst activity, i.e. measured by reaction calorimetry or thermography, may then also be used to calculate the mass of the polymer or specialty chemical produced. In addition, the change in radioactivity can be monitored over time, providing kinetic rate data, for example.

The total mass of the product is determined by methods known in the art, i.e. by calculations based on the catalyst activity or productivity, or by direct measurement of the product. Once both the radioactivity measurement, and the total mass of the product is known, the ratio of the radiolabeled comonomer in a copolymer (i.e. the comonomer content), or the ratio of the radiolabeled reagent incorporated into the product may also be determined.

In another embodiment of the invention, the same amount of catalyst is provided to each reaction region, and the total amount of radioactivity in the final product provides a direct comparison of the productivity of the catalyst. According to this embodiment, the autoradiograph will also show the relative amounts of radioactivity in each of the reaction conditions, which is particularly useful for optimizing reaction catalysts and/or reaction conditions. In a different embodiment of the invention, it is possible to study catalysts that incorporate different ratios of reagents or starting materials. For specialty chemicals, different amounts of reagents may be incorporated in the final product. In polymer chemistry, each catalyst may incorporate different proportions of monomer or comonomer in the resulting polymer. Both the amount of final product, and the radioactivity of the final product must be determined. By measuring the radioactivity of the product, it is possible to determine the amount of radiolabeled reagent that is incorporated into a specialty chemical, or in the case of polymerization reactions, it is possible to determine co-monomer content.

In an embodiment of the invention, by using two or more different radiolabeled monomers or reagents, it is also possible to determine co-monomer content in a copolymer, or the ratio of reagents incorporated in a specialty chemical. In this embodiment, different reagents or monomers contain different radiolabels. By measuring the radioactivity corresponding to each radiolabel, it is possible to determine the relative amounts of each corresponding monomer or reagent in the resulting product, i.e. polymer or specialty chemical.

Additional Analysis of Products

In one embodiment of the invention, the substrate containing the products may be placed into one or more other instruments, for analysis of the products, either before or after measuring the radioactivity. Several of these analytical methods may be performed before measuring the radioactivity, without affecting the measurement of the radioactivity.

However, if analysis of the products is performed prior to measuring the radioactivity of the products, methods that destroy the product should be avoided prior to measuring radioactivity to prevent loss of the sample. Methods to be avoided, which may destroy the sample and/or prevent the measurement of radioactivity incorporated into the product, such as mass spectrometry, elemental analysis, gas chromatography, and others are known to one of ordinary skill in the art.

The analytical instrument used may be selected from any analytical instrument that is known in the art, including but not limited to: a reaction calorimeter (i.e. used during a polymerization or reaction step), a differential scanning calorimeter, a viscosity sensor, or a mass spectrometer. Typical techniques to be used with this invention include, but are not limited to: calorimetry, mass spectrometry, viscosity measurement, thermogravimetric analysis (TGA), polarimetry, imaging polarimetry, infrared spectroscopy, IR imaging, reflectance spectroscopy, uv-vis spectroscopy, chemisorption, surface area (BET) measurements, uv-vis fluorescence, phosphorescence, chemiluminescence, Raman spectroscopy, near IR spectroscopy, magnetic resonance imaging, NMR spectroscopy, Electron Spin Resonance (ESR) spectroscopy, gas chromatography, high performance liquid chromatography (HPLC), gel permeation chromatography (GPC), temperature rising elution fractionization (TREF), x-ray diffraction, neutron diffraction, refractometry, circular dichroism, turbidimetry, electron spectroscopy, scanning electron microscopy (SEM), transmitting electron microscopy (TEM), scanning tunneling microscopy (STM) and atomic force microscopy (AFM). These techniques may be used alone, or in any combination. Other chemical and physical properties can also be measured such as magnetoresistance, conductivity, porosity, solubility, hexane extractables, weatherability, uv-vis stability, scratch resistance, abrasion resistance, wetability, hardness, color, dielectric constant, moisture absorption, drying rate, solvent swelling, gloss, adhesion, heat aging, shear, stain resistance, color fastness, scrub resistance, spreadability, emulsion stability, zeta potential, and contact angle.

Analysis of Porous Catalysts

The invention also relates to a method for the analysis of porous catalysts. For instance, according to the invention, the surface area, the number of active sites and/or metal sites, the number of acidic or basic sites, the pore size distribution, and the exchange rate of different adsorbed species and/or diffusion rates of adsorbed species can be determined. This embodiment of the invention comprises the step of providing a substrate having a plurality of reaction regions, as described above. Next, a porous catalyst is delivered to the reaction regions. The porous catalysts may be the same or different, depending on the process to be studied. For example, the invention provides a method for comparing properties of different porous catalysts. However, it is also possible to study the same catalyst, under different conditions in the reaction regions, i.e. different reagents, different amounts of activators or co-catalysts, different temperatures, etc.

The porous catalyst may be any supported catalyst, as discussed previously, which contains channels or open spaces. The channels may be microscopic or macroscopic, and there may be a variety of different size pores. The porous catalyst may further comprise naturally occurring and synthetic zeolite materials, typically comprising aluminum and silicon, and additionally boron, gallium, zirconium, titanium and trivalent metals heavier than aluminum. Additional materials may be deposited on the porous catalyst using techniques known in the art, i.e. impregnation, precipitation techniques or ion exchange. In a wet impregnation technique, the support pellets are presaturated with a solvent and immersed in the agitated solution of an active component of a certain concentration. In dry impregnation (also known as capillary impregnation), a prolonged impregnation procedure leads to equilibrium concentration of the catalyst. The porous catalyst may comprise other clays, clay oxides, silica and/or metal oxides. In a preferred embodiment, zeolites, pillared clays and molecular sieves are used. In certain cases, inactive materials may be incorporated into the porous catalyst in order to control the rate of reaction. For a general discussion of the physical chemistry of adsorption of gases and vapors on solid surfaces, as well as chemisorption and catalysis, see Adamson, A. W., Physical Chemistry of Surfaces, Second Edition, John Wiley & Sons, New York, New York (1967).

In an embodiment of the invention for determining the surface area of the catalyst, a radiolabeled compound is delivered to said reaction regions under conditions sufficient for the radiolabeled compound to be adsorbed by the porous catalyst. Typical radiolabeled reagents for such uses include Rn, Kr, and various radiolabeled hydrocarbons, such as methane, propane, ethane, cyclopropane, and others. The radiolabeled compound may be delivered, either in parallel or sequentially. Optionally, after any excess radiolabeled reagent is removed from the reaction regions, the radioactivity of the catalyst in each region may be detected and/or measured. The radioactivity of the catalyst can then be correlated to a number of physical properties, e.g., the surface area and/or the number of active sites of the porous catalyst may be determined. The radioactivity may be detected using an autoradiograph, for instance, and the detection step may be conducted either in parallel, or sequentially. Moreover, according to the invention, the method may be automated.

The invention also relates to an embodiment for determining the pore size distribution. This method comprises the steps of providing an array comprising a plurality of reaction regions, and providing a porous catalyst to the reaction regions. A mixture of radiolabeled compounds is delivered to the reaction regions under conditions sufficient for said radiolabeled compound to be adsorbed by the porous catalyst. The mixture of radiolabeled compounds comprises compounds having different molecular sizes, and wherein compounds of different molecular sizes have a different radiolabel. Typically, mixtures of radiolabeled hydrocarbons of varying molecular size and shape, such as methane, ethane, propane, cyclohexane, etc. may be used. Volatile or gaseous compounds are generally preferred. Any excess radiolabled compounds are removed from the porous catalyst in the reaction regions. By measuring the relative amounts of each radiolabel incorporated into the catalyst after adsorption of the mixture of radiolabeled compounds, it is possible to determine the pore size distribution.

In another embodiment of the invention, a method for determining the exchange rate of an adsorbed species adsorbed to a porous catalyst is provided. An array comprising a plurality of reaction regions is provided, and a porous catalyst is also provided to the reaction regions. The porous catalyst has a first radiolabeled compound adsorbed by the porous catalyst. The porous catalyst may either be delivered to the reaction region with the first radiolabeled compound already adsorbed, or the porous catalyst may first be delivered to the reaction region, and then the first radiolabeled compound will be delivered and, under appropriate conditions, adsorbed by the porous catalyst. Then, a second radiolabeled compound is provided to the reaction regions under conditions to allow a second radiolabeled compound to displace the first. To determine the exchange rate, the increase or decrease in the amount of radiation associated with the first radiolabeled absorbed compound and/or the second absorbed species is measured.

Although the present invention has been described in some detail by way of illustration for purposes of clarity of understanding, it will be apparent to those of ordinary skill in the art that various modifications and equivalents can be made without departing from the spirit and scope of the invention. It should be understood that the foregoing discussion and examples merely present a detailed description of certain preferred embodiments. All the patents, journal articles and other documents discussed or cited above are herein incorporated by reference in their entirety.

Claims

The claimed invention is: The claimed invention is:

1. A method for the synthesis and analysis of polymers, comprising the steps of: providing a substrate having a plurality of reaction regions; delivering a monomer or mixture of monomers to at least two reaction regions, wherein at least one monomer is a radiolabeled monomer; polymerizing the monomer or mixture of monomers, under conditions sufficient to form a polymer; optionally, removing any unreacted radiolabeled monomer from the reaction region; and measuring the radioactivity of the polymer in the reactor region.

2. A method of claim 1, further comprising the step of determining the yield of the polymerization reaction in the reaction regions.

3. A method of claim 1, further comprising, prior to the polymerization step, the step of delivering a catalyst to the reaction regions.

4. A method of claim 3, wherein the catalyst is selected from the group consisting of:

Zieglar-Natta catalysts, metallocene catalysts, stereospecific catalysts, constrained geometry catalysts, single-site catalysts, late transition metal single-site catalysts, free radial initiators, living free readical initiators, cationic initiators, anionic initiators, supported catalysts, unsupported catalysts and mixtures thereof.

5. A method of claim 3, further comprising the step of determining the productivity of the catalyst.

6. A method of claim 5, wherein the step of determining the productivity of the catalyst in each reaction region is performed in parallel.

7. A method of claim 3, wherein the delivery step comprises delivering a first radiolabeled monomer and a second radiolabeled monomer, wherein said first radiolabeled monomer, and said second radiolabeled monomer each comprise a different radiolabel; and wherein the polymerization step comprises polymerizing the first radiolabeled monomer and the second radiolabeled monomer, under conditions sufficient to form a copolymer, wherein the copolymer has a first radiolabeled co-monomer and a second radiolabeled co-monomer; and wherein the measuring step comprising the step of measuring the radioactivity of the first radiolabeled co-monomer, and measuring the radioactivity of the second radiolabeled co-monomer.

8. A method of claim 1, wherein the polymerization step in at least two reaction regions is performed in parallel.

9. A method for the synthesis and analysis of specialty chemicals, comprising the steps of: providing a substrate having a plurality of reaction regions; delivering a reagent or mixture of reagents to at least two reaction regions, wherein at least one reagent is a radiolabeled reagent; reacting the reagent or mixture of reagents under conditions sufficient to form a specialty chemical; optionally, removing any unreacted radiolabeled reagent from the polymer in the reaction regions; and measuring the radioactivity of the specialty chemical in the reaction regions.

10. A method of claim 9, further comprising the step of determining the yield of the reaction.

11. A method of claim 9, further comprising prior to the reaction step, the step of providing a catalyst to the reaction region.

12. A method of claim 11, further comprising the step of determining the productivity of the catalyst during the reaction step.

13. A method of claim 9, wherein the reaction step comprises at least one reaction selected from the group consisting of: hydrogenation, hydroformylation, hydroboration, hydrosilylation, hydrocyanation, carbonylation, metathesis, cross coupling, hydration, dimerization, enolization, saponification, covalent interactions, ligand binding, hydrohalogenation, condensation, decomposition, oxidation, reduction, combination, replacement, hydrolysis, and combinations of these.

14. A method for analysis of porous catalysts, comprising the steps of: providing an array comprising a plurality of reaction regions; providing a porous catalyst to at least two reaction regions; delivering a radiolabeled compound to the reaction regions under conditions sufficient for the radiolabeled compound to be adsorbed by the porous catalyst, forming a radiolabeled compound; optionally, removing any unreacted radiolabeled compound from the reaction regions; and measuring the radioactivity of the radiolabeled compound.

15. A method of claim 14, further comprising, during or after the delivery step, the step of determining the surface area of the porous catalyst.

16. A method of claim 14, further comprising, during or after the delivery step, the step of determining the number of active sites in the porous catalyst.

17. A method of claim 14, further comprising, during or after the delivery step, the step of determining the number of acidic sites in the porous catalyst.

18. A method for analysis of porous catalysts, comprising the steps of: providing an array comprising a plurality of reaction regions; providing a porous catalyst to at least two reaction regions; delivering a mixture of radiolabeled compounds to the reaction regions under conditions sufficient for the mixture of radiolabeled compounds to be adsorbed by the porous catalyst, wherein the mixture of radiolabeled compounds comprises radiolabeled compounds having different molecular sizes, and wherein radiolabeled compounds having different molecular sizes have at least one different radiolabel; optionally, removing any unadsorbed radiolabeled monomer from the reaction regions; and measuring the relative amounts of each radiolabeled compound adsorbed by the porous catalysts in the reaction regions.

19. A method of claim 18, further comprising the step of determining the pore size distribution of at least one porous catalyst.

20. A method for analysis of porous catalysts, comprising the steps of: providing an array comprising a plurality of reaction regions; providing a porous catalyst to at least two reaction regions, wherein a first radiolabeled compound is adsorbed to the porous catalyst; providing a second radiolabeled compound to said reaction regions; and measuring the exchange rate of the first radiolabeled compound for the second radiolabeled compound.