Spatially addressable method

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. 

At the end of a split synthesis, because the beads have been pooled and mixed, the exact identity of a molecule on a given bead is unknown. Likewise, the identity and structure of compounds in wells is unknown. Split synthesis is not a spatially addressable method. Fortunately, the exact structure does not need to be known unless a compound shows activity in a screen. If active, the structure of the compound in the well will need to be elucidated through a process called deconvolution. Deconvolution is generally accomplished through one of two methods recursive deconvolution21 or binary encoding.22... 

An alternative method for tracking the chemical history is encoding by spatial address. The identity of each entity is defined by its spatial address. A one-dimensional directed split-and-pool procedure, referred to as necklace coding, has been developed for synthesis carried out on SynPhase Crowns and Lanterns.13 Individual supports are strung on a Teflon thread and the position of a particle on the thread (necklace) encoded the previous chemical history (Fig. 1). A similar concept was later reported by Furka and co-workers14,15 Two-and three-dimensional encoding of the directed split-and-pool synthesis platform has been patented by Selectide Corp.16... 

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... 

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... 

The preferred mode of preparation for both mixture and split synthesis libraries is the solid phase. Both polymer matrices or pins and resin beads have been used. The solid-phase approach is preferred because of its simplicity and ease of purification and isolation of the reaction products. Unlike the spatially addressable library when structure is defined by position in a set of reaction vessels, the structure of interesting library members prepared by mixture or split synthesis must be defined by highly sensitive analytical methods or indirectly by encoding or by biological results combined with resynthesis, the so-called deconvolution method. 

Therefore, heterogeneous catalysts present a greater potential for the application of HT and Combinatorial methods, because they involve diverse compositional phases that are usually formed by interfacial reactions during their synthesis, which in turn produce a variety of structural and textural properties, often too vast to prepare and test by traditional methods. In this respect the HT and Combinatorial methods extend the capabilities of the R D cycle, which comprises the synthesis, the characterization of physicochemical properties and the evaluation of catalytic properties. The primary screening HT method gives the possibility of performing a rapid test of hundreds or thousands of compounds using infrared detection methods [27-29]. Alternatively, a detection method called REMPI (Resonance Enhanced Multi Photon Ionization) has been used, which consists of the in situ ionization of reaction products by UV lasers, followed by the detection of the photoions or electrons by spatially addressable microelectrodes placed in the vicinity of the laser beam [30, 31]. 

In essence only two approaches exist to generate combinatorial peptide libraries biologic and synthetic library approaches. According to the different techniques used, the synthetic library approach can be divided additionally into five methods 1) the spatially addressable parallel library method (1, 4, 8),... 

Other methods that are used commonly in combinatorial chemistry include attaching structures of known composition to polystyrene beads (one compound per bead) or synthesizing structures onto a inienxthip-sized matrix where a compound s location gives its identity. Tlie latter is called spatially addressable synthesis. This topic is covered in more detail in Chapter 3. 

Light-directed spatially addressable parallel synthesis, a method for the parallel... 

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