Dynamic libraries

Nitschke, J. R. Lehn, J.-M. Self-organized by selection generation of a metallosupra-molecular grid architecture by selection of components in a dynamic library of ligands. Proc. Natl. Acad. Sci. USA 2003, 100, 11970-11974. 

Figure 70 Guest-controlled assembly of PdII-linked cage-like receptors from a dynamic library generated from a Pd11 complex and two different tridentate ligands.

Rotaxanes Dynamic Libraries Self-replication Photodimerisation... 

Lehn, which was obtained from a dynamic library of hydrogen-bonding building blocks [101]. This system involved the equilibration between different products resulting from the condensation of 5,5-dimethyl-1,3-cyclohexanedione (74) and 2-hydrazinopyridine (75) (see Scheme 38). 

The examples discussed in this section provide encouraging leads for the future development of DCLs. Since a large number of biologically relevant substrates (and receptors) involve hydrogen bonding, it is certain that more templates using such interactions to amplify the formation of specific compounds from a dynamic library, will be developed in the future. 

Buryak and Severin have described the use of dynamic libraries of Cu(II) and Ni(II) complexes as sensors for tripeptides [61]. A notable aspect of this work is that as isolation of the metal complexes is not necessary (sensing is accomplished by observing changes in the UV-vis spectrum), potential concerns over the lability of coordination complexes do not apply. Specifically, three common dyes [Arsenazo I (41), Methyl Calcein Blue (42), and Glycine Cresol Red (43), Fig. 1.18] were mixed with varying ratios and total concentrations of Cu(II) and Ni(II) salts in a 4X5 array. Previous work had demonstrated that these conditions produced equilibrating mixtures of 1 1 and 2 1 homo- and heteroleptic complexes [62], These arrays were able to clearly and unambiguously differentiate tripeptides based on the differential pattern of response. The Severin laboratory has... 

Once an exchange reaction has been chosen, the researcher must next choose a set of building blocks for construction of the dynamic library. 

Zameo, S. Vauzeilles, B. Beau, J.-M. Direct composition analysis of a dynamic library of imines in an aqueous medium. Eur. J. Org. Chem. 2006, 5441-5444. 

Danieli, B. Giardini, A. Lesma, G. PassareUa, D. Peretto, B. Sacchetti, A. Silvani, A. Pratesi, G. Zunino, F. Thiocolchicine-podophyllotoxin conjugates Dynamic libraries based on disulfide exchange reaction. J. Org. Chem. 2006, 71, 2848-2853. 

Similarly, the authors also examined the stabilization effect of dynamic modification of a U-NH -appended RNA aptamer that forms a kissing complex with the HIVl transactivation-responsive RNA element TAR. In this dynamic library, 2-chloro-6-methoxy-3-quinofinecarboxaldehyde (Rd) was incorporated in place of benzaldehyde (Ra). After equilibration of the U-NHj-substituted aptamer and aldehydes Rb-Rd in the presence of the TAR RNA target, it was found that the nalidixic aldehyde Rc-appended RNA was amplified 20%, and accompanied by an increased (Fig. 3.17). Interestingly, the nalidixic aldehyde Rc was selected in both DNA and RNA complexation experiments. 

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. 

Otto, Sanders, and coworkers have utilized disulfide exchange to generate dynamic libraries of diastereomeric receptors [3]. DCLs made from a racenfic dithiol led to numerous cyclic structures including four cyclic tetramers, with the RR,RR,RR,RR diastereomer being the most stable (along with its all-5 enantiomer). Upon addition of N(CH3)J, the meso-diastereomer shown below was amplified 400-fold (Fig. 5.3). The structure of the diastereomer was confirmed by NMR and re-equilibration... 

In this chapter, it has been demonstrated that DCR is an effective method for effective kinetic screening of dynamic libraries. By combining DCLs with enzyme-mediated reactions, complete resolution of the libraries could be achieved in a one-pot process. This approach also enables screening of complex DCLs without the necessity of equimolar amounts of target molecules. 

The solver is implemented in Fortran, using optimized treatment of diagonal-band matrices and analytical derivatives of reaction rates to minimize computation time. The software structure is modular, so that different reaction-kinetic modules for individual types of catalysts can be easily employed in the monolith channel model. The compiled converter models are then linked in the form of dynamic libraries into the common environment (ExACT) under Matlab/Simulink. Such combination enables fast and effective simulation of combined systems of catalytic monolith converters for automobile exhaust treatment. 

Since the most favourable chemical fragment space for any given class of targets varies over time, we recommend planning ahead for dynamic library extensions, which may comprise target-focused fragments, new chemistries, new privileged chemical classes or... 

Certain ligand structures are certain to be favored, and others not present at all ( virtual ) [26]. Likewise, certain metal complexes are thermodynamically more stable than others. Since dynamic interconversion is possible on both covalent and supramolecular levels, both ligand and metal preferences may act in concert to amplify a limited subset of structures out of the dynamic library of all possible structures. The preparation of 1 thus represents a sorting of the dynamic combinatorial library of Figure 1.2. 

This concept may also be extended to polynuclear helicates [38]. When 2-amino-quinoline and 4-chloroaniline were mixed with the phenanthroline dialdehyde shown in Scheme 1.10, a dynamic library of potential ligands was observed to form. The addition of copper(I) causes this library to collapse, generating only dicopper and tricopper helicates. As in the mononuclear case of Scheme 1.9, the driving force behind this selectivity appeared to be the formation of structures in which all ligand and metal valences are satisfied. The use of supramolecular (coordination) chemistry to drive the covalent reconfiguration of intraligand bonds thus... 

The preparation of structure 10, shown in Scheme 1.11, requires a different kind of selectivity in the choice of ligand subcomponents. Whereas during the simultaneous formation of dicopper and tricopper helicates (Scheme 1.10) all mixed ligands were eliminated from the dynamic library initially formed, in Scheme 1.11 the mixed ligand forms the unique structure selected during equilibration [39]. 

Scheme 1.10 Simultaneous preparation of dicopper and tricopper helicates from a dynamic library of ligands.

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). 

Generation of the dynamic library proved straightforward a mixture containing equimolar amounts of the three substrates 28a-c and two equivalents of sodium pyruvate was incubated in the presence of NANA aldolase (Figures 29.2 and 29.3). Aliquots of the incubation mixture were withdrawn at intervals and analyzed by ion-exchange HPLC. 

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