Dynamic reversible chemistry

With these selected examples as context, it became clear to several laboratories in the mid-1990s that one should be able to combine reversible formation of compounds (exchange processes) and a selection method with the then rapidly developing field of combinatorial chemistry to produce equilibrating libraries that would evolve based on some selection process. Thus, dynamic combinatorial chemistry or DCC, as it came to be called, evolved from a number of lines of research into the diverse and vibrant field it is today. 

Shi, B. Greaney, M. F. Reversible Michael addition of thiols as a new tool for dynamic combinatorial chemistry. Chem. Commun. 2005, 886-888. 

Figure 3.8 Resin-bound dynamic combinatorial chemistry. Left Dynamic combinatorial building blocks immobihzed on sohd phase resin and in solution are allowed to equilibrate by reversible bond exchange to form a resin-bound dynamic combinatorial hbrary. Center The hbrary is screened against a fluorescently labeled target, and dynamic selection occurs. Right The selected hbrary members binding to the labeled target are easily visuahzed, spatially segregated, and identified.

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... 

The chemistry of superheavy elements always faces a one-atom-at-a-time situation - performing separations and characterizations of an element with single, short-lived atoms establishes one of the most extreme limits in chemistry. While large numbers of atoms and molecules are deeply inherent in the statistical approach to understanding chemical reactions as dynamic, reversible processes Chapter 3 discusses specific aspects how the behavior of single atoms mirrors properties of macro amounts. 

CDC also encompasses dynamic coordination chemistry [35, 38, 40], whereby the coordination of metal ions induces the preferential formation of specific ligand molecules and/or induces reversible changes in them. Such processes may be traced back to early work on coordination reactions of imine-based macrocyclic ligands, when now revisited in the light of constitutional dynamics [52],... 

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). 

Non-biomimetic interfaces which are constructed as they are from supramolecular associations or reversible covalent linkages. An approach to such an interface can be envisaged through the application of supramolecular chemistry and dynamic constitutional chemistry which are both conducive to adaptive structures. 

Nguyen R, Hue I (2003) Optimizing the reversibility of hydrazone formation for dynamic combinatorial chemistry. Chem Commun 8 942-943... 

Keywords Constitutional changes Covalent changes Dynamic covalent chemistry Molecular machines Molecular motors Molecular switches Polymer/monomer switches Reversible polymers Size switches... 

Once such reversible systems have been identified, it is worth the effort to find conditions for their modulation through external stimuli, ideally in a repetitive way. Examples of reversible systems come from the field of dynamic covalent chemistry [19-24] which involves covalent changes with relatively fast equilibration. 

Fig. 13 The reversible conversion (here, mediated by metal ions M) of a copolymer (A-B) into a much smaller molecule (here, a macrocycle ABM) can be seen as a size-switch which consists of a dramatic change of molecular size (molecular diameter) modulated through external stimuli, and operates through dynamic covalent chemistry. See also Fig. 15...

Moreover, reversible covalent changes (e.g. due to dynamic imine bonds) are of importance within the area of dynamic combinatorial chemistry, where they can serve as basis for the design and operation of functional materials and devices [86]. 

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. 

The synthesis of rotaxanes (and catenanes) carried out under kinetically controlled conditions has as a drawback the employment of an irreversible bond-forming final step, which may yield competitive or unwanted non-interlocked by-products. Methods allowing interlocking to occur in a thermodynamically controlled manner have therefore been developed, so that by-products can be recycled to afford the energetically, most favored, interlocked species, via reversible breakage/formation of covalent bonds ( dynamic covalent chemistry ) <2002AGE898>. 

The excellent yields of the cyclic tetramer over potentially accessible larger structures have been demonstrated to result from thermodynamic product control under equilibrating conditions <2006OL2755, 2006TL4041>. The facile and selective formation of a specific molecule in a thermodynamically controlled reaction, where the covalent bond has the ability to be formed and reversibly broken, is the subject matter of dynamic covalent chemistry <2002AGE898>. 

Aldol addition has a low activation energy, a potentially important consideration in dynamic covalent chemistry (reactions carried out reversibly, under conditions of equilibrium control). ... 

Recently, the French Nobel prizewinner Jean-Marie Lehn proposed the use of CTI as a source of molecular diversity in dynamic combinatorial chemistry. The prospect of using a dynamic fully reversible process such as CTI for the evolutionary selection of ligands is extremely attractive and should lead to fundamental advances in this field of research. 

It was recently suggested that carbamate bonds could be employed for a wider variety of dynamic covalent chemistry (DCC) experiments (88) and DCC is quickly emerging as a promising alternative to noncovalent self-assembly (91). This experiment offers an elegant opportunity of performing supramolecular chemistry with covalent bonds. One of the most important advantages here is the robustness of covalently organized structures, which on the other hand can be reversibly broken, at will. Of particular interest are supramolecular polymers and supramolecular materials. 

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