Parallel Synthesis and Positional Encoding

In contrast with the split/pool method, parallel synthesis does not require encoding, produces discrete compounds in measurable quantities, and allows for collection of a full SAR. It is becoming increasingly popular among other combinatorial methods. 

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Diversity Sciences developed a library synthesis strategy that combines the simplicity of parallel synthesis and the power of resin-mixing techniques. The general format is four 96-well plates that give rise to 384 synthetic wells, as shown in Figure 8.9. The layout of the synthesis blocks enables 16 unique monomers in monomer position A (across rows) and 24 unique monomers in monomer position B (down the columns). All of the 384 wells are preloaded with off-the-shelf resin where each well has a unique binary code embedded in the analytical construct. The first two points of diversity (monomer A and monomer B) is added in all possible combinations by parallel synthesis. Each spatial location has a unique binary-mass code that encodes for a particular combination of monomer A and monomer B. For example, binary code number 8 represents monomer Al and monomer B8. After the addition of monomer B, the resin from all 384 wells is mixed together and split into 96 identical pools, to which monomer C is added. The third monomer, monomer C, is spatially encoded, since the 96 pools are not mixed after the last step and screened as pools. Upon decoding, the identification of the binary code reveals the combination of monomer A and monomer B on each bead. 

Most approaches described in the literature for the synthesis of complex oxides deal with parallel or fast sequential synthesis by the aid of robotic systems. The variability of synthetic procedures employed ranges from gas phase deposition methods pioneered by the initial work of Hanak [5,6] and other authors who used the basic principle and refined the synthetic technique with regard to the deposition features and the chemistries employed [7-9]. Typical deposition techniques use several source materials and spatial resolution is mostly achieved via masking techniques. An essential feature of these synthetic approaches is the fact that a plurality of compounds is generated on a single substrate so that the result of the synthetic procedure is a substrate-bound library, where the position of each library member encodes the synthetic information, as composition or other synthetic steps that the material has been subjected to. 

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