Dynamic combinatorial chemistry DCC

Dynamic combinatorial chemistry (DCC) is marvelously effective at discovering receptors for a broad array of analytes. The nature of the internal competition experiment ensures (normally) that the most effective binder for the analyte of interest is amplified for subsequent identification and characterization. In the context of a host-guest assembly, the issue of stereochemistry can be manifested in a number of scenarios. These include various permutations of chiral or achiral guests, along with achiral, enan-tiopure, or racemic dynamic library components. 

Dynamic combinatorial chemistry (DCC) is a rapidly emerging field that offers a possible alternative to the approach of traditional combinatorial chemistry (CC).32 Whereas CC involves the use of irreversible reactions to efficiently generate static libraries of related compounds, DCC relies on the use of reversible reactions to generate dynamic mixtures. The binding of one member of the dynamic library to a molecular trap (such as the binding site of a protein) is expected to perturb the library in favor of the formation of that member (Figure 29.1). 

FIGURE 29.1 The dynamic combinatorial chemistry (DCC) concept reversible reactions performed with a limiting amount of X generate a mixture of compounds AX, BX, and CX. The binding of AX to molecular trap T causes perturbation of the equilibria involving A and X to give overall amplification of AX at the... 

Dynamic combinatorial chemistry (DCC) is founded on the study and the construction of mixtures of discrete constituents which are produced by reversible molecular or supramolecular associations [1, 2], The composition of a dynamic combinatorial library (DCL) is thermodynamically driven and, as such, is able to adapt itself to any parameter that - permanently or transiently - modifies its constitution/energy potential surface [3,4], Thus, in the presence of various internal or external parameters, the involved equilibria can be displaced toward the amplification of given products through an adaptation process that will occur through an in situ screening of these species. A schematic representation using Emil Fisher lock-and-key metaphora can be used to illustrate these concepts (Fig. 1). 

This dynamic process is commonly known as constitutional dynamic chemistry (CDC). While the concept of dynamic covalent chemistry defines systems in which the molecular (or supramolecular) reorganization proceeds via reversible covalent bond formation/breakage, dynamic systems based on noncovalent linkage exchanges define the concept of dynamic noncovalent chemistry. Dynamic combinatorial chemistry (DCC) can be defined as a direct application of CDC where libraries of complementary functional groups and/or complementary interactional groups interexchange via chemical (i.e., covalent) reactions or physical (i.e., noncovalent) interactions. 

This conceptually different approach resides in dynamic combinatorial chemistry (DCC). It is based on dynamically generated combinatorial libraries (DCLs), which are virtual in their generality, the actual constituents present at any moment being just the real sub-set of all those that are potentially accessible ). Its main features are summarized in Fig. 1, in comparison to those of CLs themselves. 

Finally, dynamic combinatorial chemistry (DCC) opens new perspectives for templated syntheses. Early work was accomplished by the late M. Nelson, who studied in detail the condensations between diamines and 2.6-diacetyl-pyridine in the presence of various metal cations. To conclude, he found that the macrocyciic compounds formed depend on the overall proportions of the reactants and the type of cation used as the template. Related studies were accomplished using pyridine dialdehyde and several diamines (Fig. 22). ... 

Dynamic combinatorial chemistry (DCC) Effective molarity (EM) Equilibrium macrocyKzations allosteric cooperativity, 48—51 factor, 49, 50f... 

See also Cooperativity Dynamic combinatorial chemistry (DCC) assembly of cooperative supramolecular complex, 80f... 

The value of the dynamic combinatorial chemistry (DCC) approach has been demonstrated by some interesting examples that reveal receptors with exceptionally strong affinities for the target [8]. 

The basic concepts of selection experiments with dynamic combinatorial libraries (DCLs) were articulated more than 10 years ago (see Chapter 1). Since then, a number of applications have emerged. This includes the discovery new enzyme inhibitors, receptors, and catalysts, as well as the synthesis of novel materials such as responsive gels and polymers (see Chapters 2-5). A recent addition to the list of applications is the utilization of dynamic combinatorial chemistry (DCC) for analyhcal purposes. This chapter summarizes the main ideas and results in this area. 

Interest in dynamic combinatorial chemistry (DCC) has increased rapidly since the first publications on the subject in the mid-1990s. Figure 8.1 shows that the annual number of publications involving DCC has risen steadily. Among the various available reversible covalent reactions, disulfide, imine, and hydrazone chemistries are the most popular (Figure 8.2). However, other reversible covalent reactions are being developed and there is definitely a need to further expand this repertoire. 

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. ... 

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