Dynamic combinatorial library approach

The dynamic combinatorial library approach can also be employed using solid-state substrates with the templating fragments attached to them with suitably long linkers." In addition to the templating effect that the active fragment maintains on the surface and dropped out into the... 

Using this approach, a dynamic combinatorial library (DCL) of rapidly equilibrating metal complexes was formed by incubating a series of salicylaldimines with the transition metal salt ZnCl in aqueous solution (Fig. 3.3). Divalent zinc was chosen as the transition metal for its known tetravalent coordination geometry with salicylaldimines [7] and its compatibility with DNA. (In retrospect, this was a somewhat naive view of both... 

Dynamic combinatorial libraries (DCLs) are continuously interconverting libraries that evenmally evolve to an equilibrium distribution [61-65]. This approach has been used successfully in the discovery of stable supramolecular assemblies from mixtures. Due to the nearly endless possible peptide sequences that can potentially be synthesised, the DCL approach is attractive for the identification of supramolecular peptide interactions. Indeed, disulfide exchange between cysteine residues has been explored for this purpose [66, 67] as has peptide-metal binding [68]. We have recently demonstrated protease-catalysed amide exchange in this context, which allows for the evolution of the self-assembled peptide structures, and will therefore allow exploration of peptide sequence space for biomaterials design. 

The use of anions as templating agents is discussed by Vilar. The chapter starts with a general overview of the area and a discussion of the applications of anion templates in organic and coordination chemistry. The second part of the chapter deals with examples where anions are employed as templates in dynamic combinatorial libraries. This approach promises to provide an efficient route for the synthesis of better and more selective anion receptors. The last chapter by Ewen and Steinke also deals with the use of anions as templates but in this case in the context of molecular imprinted polymers. The first half of the chapter provides an introduction into molecularly imprinted polymers and this is followed by a detailed discussion of examples where anionic species have been used to imprint this class of polymeric materials. 

Constable. E.C. Housecroft. C.E. Kulke, T. Lazzarini. C. Schofield, E.R. Zimmermann, Y. Redistribution of terpy ligands—Approaches to new dynamic combinatorial libraries. J. Chem. Soc.. Dalton Trans. 2001. 2864-2871. 

It is evident from Chapters 3 and 5 that dynamic combinatorial libraries (DCLs) have indeed become popular and powerful tools for these purposes. The responsiveness of DCLs to external influences has also potential for other applications. First reports on the influence of electric flelds [9], light [10-12], and temperature and pH [13] have recently appeared, and it is our expectation that there is a great deal more to be discovered by using these and other external stimuli. The same applies to the use of DCLs for identifying catalysts (see Chapter 4). The dynamic combinatorial approach has not yet seriously entered this area of science and only the first examples have appeared that show proof-of-principle. It is possible to design procedures to select a catalyst from a dynamic mixture of candidate molecules. 

Dynamic combinatorial chemistry (DCC) has proven extremely useful in creating complex mixtures of interchanging compounds termed dynamic combinatorial libraries (DCL). Key to the formation of such DCLs is a reversible chemical process that allows the library members to interconvert. The formation of imines from aldehydes and amines is a prominent example for the creation of a DCL. Since the overall distribution of compounds is under thermodynamic control, external stimuli can be used to bias the DCL toward a specific member of the library. This approach has been exploited successfully in the search of potent receptors for molecules of pharmacological interest, the creation of supramolecular assemblies, and ligands for biomacromolecules. ... 

In this work, they describe a general approach for the synergistic relationships that exist at two length scales within a self-replicating dynamic combinatorial library. They show that molecnlar constituents can compete at the subnanometer scale for the reversible production of amphiphiUc dynamic block copolymers or surfactants (i.e., dynablocks, which are defined as species combining a hydrophobic and a hydrophilic moiety linked together by a reversible connection). The packing parameters of the condensed dynablocks determine the formation and the thermodynamic stability of... 

Supramolecular chemistry thus has a direct relationship with the highly active area of combinatorial chemistry, however in a very specific fashion. Indeed, reversibility being a basic and crucial feature of supramolecular systems, the dynamic generation of supramolecular diversity from the reversible combination of noncovalently linked building blocks falls within the realm of the emerging area of dynamic combinatorial chemistry (DCC) which involves dynamic combinatorial libraries, of either virtual (VCL) or real nature depending on the system and the conditions [45,46], The concepts and perspectives of the DCCA CL approach have been outlined, inter alia with respect to supramolecular polymers [45],... 

Figure 3.17 Approach to the dynamic combinatorial modification of the TAR-binding aptamer. Left, italics The TAR RNA sequence. Left, bold The TAR-binding aptamer. Left, boxed The 2 -amino-2-deoxyuridine (U-NH ) for dynamic RNA modification. Left center Rb—Rd, the aldehyde library components. Right center Imino-linked DCL members. Right The selected nalidixic aldehyde appended to U-NH results in the TAR RNA-aptamer complex stabilization.

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