Synthesis high-throughput

Glass BM, Combs AP (2001) In Sucholeiki 1 (ed) High-Throughput Synthesis. Principles and Prachces. Marcel Dekker, New York... 

Wyss PC, Gerber P, Hartman PG, Hubschwerlen C, Locher H, Marty HP, Stahl M. Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening. J Med Chem 2003 46 2304-12. 

Guerin S, Hayden BE. 2006. Physical vapor deposition method for the high-throughput synthesis of solid-state material libraries. J Comb Chem 8 66-73. 

Guerin S, Hayden BE, Lee CE, et al. 2006a. High-throughput synthesis and screening of ternary metal alloys for electrocatalysis. J Phys Chem B 110 14355-14362. 

Hammer-Nprskov d-band model, 70, 272-273, 327 Heme-copper oxidase, 610 High Throughput Synthesis of Nanoparticles, 572-574 Hydrogen (underpotential) adsorption, 60-63,254, 471-484, 526 Hydrogen evolution reaction (HER), 31, 79-87... 

Hahndorf, I., Buyevskaya, O.V., Langpape, M. et al. (2002) Experimental equipment for high-throughput synthesis and testing of catalytic materials. Chem. Eng. J., 89, 119. 

Cong, P., Doolen, R., Fan, Q. et al. (1999) High-throughput synthesis and screening of combinatorial heterogeneous catalyst libraries. Angew. Chem. Int. Ed., 38, 484. 

MultiPREP rotors (Fig. 3.7) For high-throughput synthesis, Milestone offers a series of different parallel rotors for 36, 50 or 80 glass or Teflon-PFA vessels (35/50 mL) to perform reactions at atmospheric pressure up to 230 °C. 

Parallel processing of synthetic operations has been one of the cornerstones of medicinal and high-throughput synthesis for years. In the parallel synthesis of compound libraries, compounds are synthesized using ordered arrays of spatially separated reaction vessels adhering to the traditional one vessel/one compound philosophy. The defined location of the compound in the array provides the structure of the compound. A commonly used format for parallel synthesis is the 96-well microtiter plate, and today combinatorial libraries comprising hundreds to thousands of compounds can be synthesized by parallel synthesis, often in an automated fashion. 

Several articles in the area of microwave-assisted parallel synthesis have described irradiation of 96-well filter-bottom polypropylene plates in conventional household microwave ovens for high-throughput synthesis. While some authors have not reported any difficulties in relation to the use of such equipment (see Scheme 4.24) [77], others have experienced problems in connection with the thermal instability of the polypropylene material itself [89], and with respect to the creation of temperature gradients between individual wells upon microwave heating [89, 90]. Figure 4.5 shows the temperature gradients after irradiation of a conventional 96-well plate for 1 min in a domestic microwave oven. For the particular chemistry involved (Scheme 7.45), the 20 °C difference between the inner and outer wells was, however, not critical. 

B. M. Glass, A. P. Combs, in High-Throughput Synthesis. Principles and Practices... 

B. M. Glass, A. P. Combs, Case Study 4-6 Rapid Parallel Synthesis Utilizing Micro-wave Irradiation, in High-Throughput Synthesis. Principles and Practices (Ed. I. Sucholeiki), Marcel Dekker, Inc., New York, 2001, Chapter 4.6, pp 123—128. 

Apart from the traditional organic and combinatorial/high-throughput synthesis protocols covered in this book, more recent applications of microwave chemistry include biochemical processes such as high-speed polymerase chain reaction (PCR) [2], rapid enzyme-mediated protein mapping [3], and general enzyme-mediated organic transformations (biocatalysis) [4], Furthermore, microwaves have been used in conjunction with electrochemical [5] and photochemical processes [6], and are also heavily employed in polymer chemistry [7] and material science applications [8], such as in the fabrication and modification of carbon nanotubes or nanowires [9]. 

Y-FMOC-AMINOOXY-2-CHLOROTRITYL POLYSTYRENE RESIN FOR HIGH THROUGHPUT SYNTHESIS OF HYDROXAMIC ACIDS... 

Fig. 10.4 Diagram outlining criteria for successful use of high-throughput synthesis/screening approaches to materials discovery and exploration.

Our research using the CCS approach has focused on the discovery of new dielectric thin films. This example illustrates the power of this approach and key considerations in utilizing high throughput synthesis and screening approaches. A variety of other problems appear well matched to such combinatorial-style methods. A few of these are discussed briefly below, touching on both experimental challenges and research opportunities. 

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