Ensuring Meaningful Amplifications

The power of DCC for the discovery of new synthetic receptors depends in part on the original conception that the best hosts in a DCL would be most amplified upon 

Despite these and various other examples of molecular amplification of receptors described during the last 12 years, the amplification of the fittest concept 

In summary, to ensure selective amplification of the best receptor it is important that the concentration of template molecules does not demand more molecules of the preferred building blocks than the system can provide. This can be achieved by using low concentration of templates or by keeping an in situ building block feedstock. This feedstock can be free building blocks (virtual libraries) or building blocks as part of nonbinding assemblies (sublibraries). 

A second original concept from the early years of DCC was that exposure of a given DCL of receptors to a variety of guests that amplify the same receptor would produce responses from the libraries that correlate with the binding of those guests to the ampUfied receptor. Again, some early results on amplification of receptors from relatively simple DCLs supported that idea. 

Adding aUcaU metal iodide salts as templates induced modest changes in product distribution [36]. The most significant shift in library composition was induced by sodium iodide, which doubled the concentration of tetramer and pentamer in the reaction mixture. Binding constants were not measured however, the relative affinities of the amplified cyclophane macrocycles for the different metal alkali were studied by electrospray ionization-mass spectrometry (electrospray ionization ESI-mass spectrometry MS), finding good agreement with the main amplification observed. The yield of cychc tetramer was increased by the addition of sodium in the cases of the MEM and di(p-methoxybenzyl) monomers, and these were found to bind sodium preferentially in the ESl-MS study [109]. 

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