Spatially addressable

Pirrung, M.C., Spatially addressable combinatorial libraries, Chem. Rev., 1997, 97, 473-488. 

The use of planar supports for presenting large arrays of spatially addressed molecules is one of the most powerful and versatile methods for creating combinatorial libraries.19,28-29 

Scharn, D., Wenschuh, H., Reineke, U., Schneider-Mergener, J. and Germeroth, L., Spatially addressed synthesis of amino- and amino-oxy-substituted 1,3,5-triazine arrays on polymeric membranes, /. Comb. Chem., 2000, 2, 361. 

Fodor, S. P. (1991). Light-directed, spatially addressable parallel chemical synthesis. Science 251, 767-773. 

I-odor. S P A. 01 at. "Light-Directed. Spatially Addressable Parallel Chemical Synthesis.". Vcienee, 767 (February IS. 19911 Jam>ld. M.F. "Nanosurfaee Clietnisiry on Size-Selected Silicon C liniers." Seitner. 1085 tMay 14. 1991). 

Their components are produced typically in a spatially addressable format requiring no deconvolution or encoding strategies for identification of active components making for very quick analysis of SAR. 

In-situ photofabrication of OND arrays involves light-directed, spatially addressable, parallel (combinatorial) chemical synthesis [35,43,66-68]. A surface, usually a sihcon wafer or a glass slide, is coated with hnker molecules 

Direct electrochemical amide oxidation reactions have also been employed in parallel synthesis using a spatially addressable electrochemical platform [107]. In this work, an electrolysis platform was set up so that 16 electrochemical reactions could be run in parallel at the same time. The cells were set up in a 4 by 4 array in which each cell was equipped with a 

Parallel synthesis is the term loosely applied to the preparation of discrete compounds in the format of a spatially addressable array. It is often used in contrast to "mixture-based" combinatorial synthesis. While it is hue that the term "parallel synthesis" may encompass the preparation of a fully combinatorial multidimensional array of compounds, in practice, it most 

The experiments described above demonstrate the ability to deliver soluble analytes to bilayer arrays and to evaluate the ability of these species to prevent surface absorption of proteins. Therefore, we have demonstrated methods of creating spatially addressed arrays of aqueous solutions above phospholipid membranes as well as arrays of phospholipid membranes with unique chemistry in each bilayer.13 These two concepts were carried out in separate assays. To be able to control both surface chemistry and aqueous chemistry 

In a different approach three different structurally defined aza-crown ethers were treated with 10 different metal salts in a spatially addressable format in a 96-well microtiter plate, producing 40 catalysts, which were tested in the hydrolysis of /xnitrophenol esters.32 A plate reader was used to assess catalyst activity. A cobalt complex turned out to be the best catalyst. Higher diversity is potentially possible, but this would require an efficient synthetic strategy. This research was extended to include lanthanide-based catalysts in the hydrolysis of phospho-esters of DNA.33 

Other terms also relate to the anatomy of the microarray (Figure 1.4). The probes are immobilized on the substrate at discrete (x, y) locations or spatially addressable sites. The probe spots [measured in microns (diameters) for a circular spotted array or as a side of a square for an in situ array] are often referred to as features or elements of an array. Thus, an array containing 10,000 features would have 10,000 probes arranged as an array on a substrate. 

As first practiced by Geysen and Houghton, the preparation of combinatorial libraries produced discrete compounds of known identity through a technique known as "spatial separation," which simply means that individual compounds in the library are produced discretely and are not mixtures. Such spatially addressable compound sets are produced in such a way as to keep separate the reaction flasks or resin beads containing the individual components of the library and perform bioassays on the discrete compounds, one at a time. Thus, if the "history" of the reaction conditions performed in each flask or on each solid support, the identity of the compounds produced is known, without resort to structure elucidation techniques. Initially, this technique, after typically an extensive reaction development stage, allowed the preparation of between 10 and 1000 discrete combinatorial products. 

In the future, further studies should be addressed to improve the chemose-lectivity and diastereoselectivity of the reductive coupling process, especially searching for novel reagents and milder experimental conditions. As a matter of fact, a few novel reductive couphng procedures which showed improved efficiency and/or stereoselectivity have not been further apphed to optically active imines. For example, a new electrochemical procedure which makes use of the spatially addressable electrolysis platform with a stainless steel cathode and a sacrificial aluminum anode has been developed for imines derived from aromatic aldehydes, and the use of the N-benzhydryl substituent allowed 1,2-diamines to be obtained with good yields and dl-to-meso ratios 

In Scheme 9.4, a three-component synthesis using an amine, acid chloride, and alkyl halide is shown. If this process were started with two amines (Ai and A2), two acid chlorides (Cj and C2), and two alkyl halides (Hj and H2), eight (23) new amides may be formed (Scheme 9.5). Such a synthesis would require eight wells. The reagents would be dispensed in a pattern to generate all possible combinations. At the end of the synthesis, the exact position and contents of each well would be known. Therefore, parallel synthesis is often referred to as a spatially addressable method. Any particular compound may be accessed directly and immediately. 

Several combinatorial approaches to the discovery of transition metal based catalysts for olefin polymerization have been described. In one study Brookhart-type polymer-bound Ni- and Pd-(l,2-diimine) complexes were prepared and used in ethylene polymerization (Scheme 3).60,61 A resin-bound diketone was condensed with 48 commercially available aminoarenes having different steric properties. The library was then split into 48 nickel and 48 palladium complexes by reaction with [NiBr2(dme)] and [PdClMe(COD)], respectively, all 96 pre-catalysts being spatially addressable. 

Regardless of how the products are isolated and purified, all parallel syntheses hold to the concepts of one compound-one well and spatial-addressability. Differences between various parallel syntheses are discemable based on whether the synthesis is performed in a solution-phase or solid-phase manner. 

FIGURE 6.3. (a) A schematic representation of a 2 X 2 array of addressed supported fluid biomembranes with various components in each box. The right-hand side (b) An epifluorescence image of a 3 x 3 array of fluid biomembranes that have been addressed using the spatial addressing techniques described above. 

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