Constitutional dynamic library

A set of interconverting supramolecular or molecular entities represents a real or virtual [35, 42] constitutional dynamic library (CDL). The full ensemble of all constituents, i.e., of all possible combinations of the components, may be termed the combinome of the system under consideration. The set of components may be considered as the genotype of the dynamic system and the sets of constituents generated from these components in given conditions its phenotypes. 

Evolution of a constitutional dynamic library of dynamer strands may be driven by metal ion binding towards the generation of a specific metallo-supramolecular architecture, such as a [2x2] grid [54], or of a dynamer presenting specific interactions and properties (such as optical self-sensing) [57] (see also Figs. 7 and 8 in [9]). 

Along another line of thought, one might also consider that the ability of a constitutional dynamic library to generate potentially all virtual constituents represents a sort of superposition of all states of the system corresponding to a given combination of the initial components. The conditions determine which state/ combination/constituent becomes/is observable. 

Fig. i Constitutional dynamic chemistry applied to bovine carbonic anhydrase bCA II isozyme and elaboration of constitutional dynamic library (CDL). Precursor amines a-d and aldehydes 1-3 and resulting components of the combinatorial library Ia-c-3a-c. HPLC traces of the final reaction mixtures showing amplification of 3c and 3d (adapted from [49])... 

In this context the constitutional dynamic library (CDL) is susceptible to change its composition (output expression) through component selection driven by the... 

Fig. 3 Elaboration of the DCL of inhibitors inhibition constants K and the amplification of the constitutional dynamic library (CDL) against catalytically active human hCA I and hCA II cytosolic isozymes (adapted from [66])...

Other terms have been employed for this general concept, including self-assembled combinatorial libraries, constitutional dynamic chemistry, and virtual combinatorial libraries . Dynamic combinatorial chemistry and dynamic combinatorial library seem to have found the broadest usage, while virtual combinatorial library is perhaps best reserved for conditions under which library members form at concentrations below detection limits in the absence of target (e.g.. Reference 81). 

Numerous studies have been performed on the dynamic generation from DCLs of either molecular receptors for substrates or substrates for receptors [35-39, 46]. Work in our group has been directed in particular towards the influence of physical and chemical stimuli on the behavior of DCLs, as for instance in the case of the constitutional dynamic reorganization exerted by temperature and protonation on imine libraries [45], the induction of liquid crystal properties by an electric field acting on a dynamic library [47], or component selection induced by cation binding in a folded dynamer chain [48] (see also below). 

A particularly illustrative case is that of induced fit expression/amplification of a receptor by selection among an interconverting set of entities, enforced by substrate binding, in a triple dynamic library (constitutional, configurational, and conformational) (Fig. 4) [49]. 

Fujii S, Lehn JM (2009) Structural and functional evolution of a library of constitutional dynamic polymers driven by alkali metal ion recognition. Angew Chem Int Ed Engl 48 7635-7638... 

CA Carbonic anhydrases CDC Constitutional dynamic chemistry DCC Dynamic combinatorial chemistry DCL Dynamic combinatorial library(ies)... 

These concepts were first developed and described by Lehn [67] and Giuseppone [11]. The constitutional recomposition of a dynamic library of imines can display complex behavior under the effect of two external parameters a physical (T) stimulus and a chemical effector ([H+]) [67]. These results illustrate the possibility of modulating an optical by constitutional recomposition induced by a specific trigger. Such features have been used for the development of stimuli-responsive, functional dynamic materials. 

Keywords Dynamic combinatorial library Constitutional dynamic chemistry Reversible reactions Supramolecular chemistry Thermodynamic control... 

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. 

It follows from the previous considerations that supramolecular polymer chemistry is both dynamic and constitutionally diverse. Supramolecular polymers present dynamic constitutional diversity and are therefore constitutional dynamic materials (CDMs) belonging to the realm of constitutional dynamic chemistry (CDC) [4], They are based on dynamic polymer libraries whose constituents have a constitutional diversity determined by the number of different monomers (see Section III). Similar views apply to supramolecular liquid crystals. 

Application of the considerations above to polymer chemistry leads to the definition of constitutionally dynamic polymers, dynamers, of both molecular and supramolecular types (Fig. 1) [29-32]. They behave as dynamic combinatorial entities, based on dynamic libraries whose constituents have a combinatorial diversity determined by the number of different monomers. The components incorporated by polyassociation or by polycondensation into the supramolecular or molecular polymer chains depend on the nature of the connections (recognition patterns or functional groups) and core groups, as well as on the interactions with the environment, so that dynamers possess the capacity of adaptation by association/growth/ dissociation sequences. 

Lehn and coworkers reported a series of reactive diene and pentafulvenes involving reversible Diels-Alder reactions at ambient temperature. The results provide a foundation for the implementation of the reversible Diels-Alder reaction in constitutional dynamic chemistry (Scheme 7.26) [27]. With variation of the functionalized substituted fulvenes 108 and cyanoolefin esters 109, the methodology may be applied for the preparation of dynamic combinatorial libraries and provides an entry to reversible dynamic polymers and the discovery of biologically active substances. 

Multiple Expressions of Target-Encoded Dynamic Constitutional Libraries. 35... 

In this context the supramolecular crystalline [15-22] or hybrid materials [23-35] can be prepared and constitutionally self-sorted by using an irreversible kinetic process like crystallization or sol-gel polymerization. The self-selection is based on constitutional internal interactions of library components, resulting in the dynamic amplification of self-optimized architectures, during the phase change process. With all this in mind, the second part will be devoted to sol-gel resolution of dynamic molecular supramolecular libraries, emphasizing recent developments, especially as pursued in our laboratory. 

Complex dynamic and positive feedback between molecular/supramolecular partners in dynamic combinatorial libraries (DCLs) gives rise to emergent functional systems with a collective behavior. From the conceptual point of view, these systems express a synergistic constitutional self-reorganization (self-adaptation) of their configuration, producing an adaptive response in the presence of internal or external structural factors. 

Barboiu M, Petit E, van der Lee A, Vaughan G (2006) Constitutional self-selection of [2x2] homonuclear grids from a dynamic combinatorial library. Inorg Chem 45 484 186... 

Nasr G, Petit E, Vullo D, Winum JY, Supuran CT, Barboiu M (2009) Carbonic anhydrase-encoded dynamic constitutional libraries towards the discovery of isozyme-specific inhibitors. J Med Chem 42 4853 -859... 

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). 

Giuseppone N, Schmitt J-L, Allouche L, Lehn J-M (2008) DOSY NMR experiments as a tool for the analysis of constitutional and motional dynamic processes implementation for the driven evolution of dynamic combinatorial libraries of helical strands. Angew Chem Int Ed 47 2235-2239... 

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