Self-assembly dynamic combinatorial library

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). 

Kay Severin s group has previously investigated the preparation of dynamic combinatorial libraries of metallo-macrocycles for use as sensors for Li+ at physiologically relevant conditions [59]. For example, they have found that ligand 62 and metal complexes 63 undergo a self-assembly process to yield the trimeric complexes depicted in Scheme 4.15 [60]. Mixtures of 64 and... 

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. 

FLUXIONAL SELF-ASSEMBLY AND DYNAMIC COMBINATORIAL LIBRARIES... 

Five bis-calecholate ligand syntones (Scheme 4.119) have been used [116] to evaluate combinatorial libraries of their coordination self-assemblies with metal ions as hosts for various guests. As follows from ESI-MS and NMR data, the dynamic combinatory library with many assemblies simultaneously being present in a solution is made from labile ligand syntones and... 

Hue, I. Lehn, J. M. Virtual combinatorial libraries Dynamic generation of molecular and supramolecular diversity by self-assembly. Proc. Natl. Acad. Sci. U.S.A. 1997,94,2106-2110. 

Fig. 6 Dynamic combinatorial peptide library that expioits enzyme reactions to control self-assembly processes under thermodynamic controi. (a) Emergence of the potentiai peptide derivatives of varying length in a library of interconverting molecules formed from the staring materials of Fmoc L/L2 system. Fmoc-Ls is preferentially formed. Corresponding AFM images of the fibrillar structures formed at 5 min after the addition of enzyme, and the sheet-like structures observed after 2000 h show that redistribution of the derivatives is accompanied by the remodelling from fibres (Fmoc L3) to sheet-like structures (Fmoc L5). (b) HPLC analysis of the composition of the system reveals the formation and the stabilisation of Fmoc-Ls over time. Modified from [21]...

For dynamic processes involving hydrogen-bonded entities, see (a) Calama MC et al (1998) Libraries of non-covalent hydrogen-bonded assemblies combinatorial synthesis of supramolecular systems. Chem Commun 1021-1022. (b) Timmerman P et al. (1997) Noncovalent assembly of functional groups on Calix[4]arene molecular boxes. Chem Eur J 3 1823-1832. (c) Cai MM et al. (2002) Cation-directed self-assembly of lipophilic nucleosides the cation s central role in the structure and dynamics of a hydrogen-honded assembly. Tetrahedron 58 661-671... 

Template-directed synthesis has also been exploited for combinatorial purposes in which a reversible reaction and the use of thermodynamic templates have been used. Two different processes have been envisaged and validated, both of which consider the dynamic optimization of a receptor-ligand interaction where one of the partners is the template that drives the self-assembly of a reversible library of other partners from which the best binder for the template is selected (Fig. 8.53). If the receptor is a template, a library made using a reversible reaction is incubated with the receptor and... 

Fig. 3. Dynamic generation of virtual combinatorial libraries. Top Casting process receptor-induced self-assembly of the complementary substrate from a collection of components serving as building blocks it amounts to the selection of the optimal substrate from a virtual substrate hbrary. Bottom Molding process substrate-induced self-assembly of the complementary receptor from a collection of structural components it amounts to the selection of the optimal receptor from a virtual receptor Hbrary. The diverse potential constituents of the Hbraries center, top and bottom) are either covalently Unked or noncovalently bound, reversibly generated species that may or may not exist in significant amount(s) in the free state, in absence of the partner. The components may either be directly connected or assemble reversibly on polyfunctional supporting frameworks of various structural types.

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