Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor

We report the one-pot amplification and isolation of a nanomolar receptor in a multibuilding block aqueous dynamic combinatorial library using a polymer-bound template. By appropriate choice of a poly(N,N-dimethylacrylamide)-based support, unselective ion-exchange type behaviour between the oppositely charged cationic guest and polyanionic hosts was overcome, such that the selective molecular recognition arising in aqueous solution reactions is manifest also in the analogous templated solid phase DCL syntheses. The ability of a polymer bound template to identify and isolate a synthetic receptor via dynamic combinatorial chemistry was not compromised by the large size of the library, consisting of well over 140 theoretical members, demonstrating the practical advantages of a polymer-supported DCL methodology

Probing the limits of selectivity in a recognition-mediated reaction network embedded within a dynamic covalent library

This work was supported by the award of a Postgraduate Studentship from EPSRC (EP/K503162/1) to TK.Two recognition-mediated reaction processes operating through a reactive binary complex drive resolution of a 24-component dynamic covalent library, assembled from individual aldehydes and nucleophiles. The effectiveness of the library resolution and selective amplification of one recognition-enabled species over another is limited by the difference in the rates of the recognition-mediated reactive processes and strength of the recognition processes employed in the dynamic system.PostprintPeer reviewe

Template-Directed Synthesis of Multiply Mechanically Interlocked Molecules Under Thermodynamic Control

The template-directed construction of crown-ether-like macrocycles around secondary dialkylammonium ions (R2NH2+) has been utilized for the expedient (one-pot) and highyielding synthesis of a diverse range of mechanically interlocked molecules. The clipping together of appropriately designed dialdehyde and diamine compounds around R2NH2+-containing dumbbell-shaped components proceeds through the formation, under thermodynamic control, of imine bonds. The reversible nature of this particular reaction confers the benefits of “errorchecking” and “proof-reading”, which one usually associates with supramolecular chemistry and strict self-assembly processes, upon these wholly molecular systems. Furthermore, these dynamic covalent syntheses exploit the efficient templating effects that the R2NH2+ ions exert on the macrocyclization of the matched dialdehyde and diamine fragments, resulting not only in rapid rates of reaction, but also affording near-quantitative conversion of starting materials into the desired interlocked products. Once assembled, these “dynamic” interlocked compounds can be “fixed” upon reduction of the reversible imine bonds (by using BH3·THF) to give kinetically stable species, a procedure that can be performed in the same reaction vessel as the inital thermodynamically controlled assembly. Isolation and purification of the mechanically interlocked products formed by using this protocol is relatively facile, as no column chromatography is required. Herein, we present the synthesis and characterization of 1) a [2]rotaxane, 2) a [3]rotaxane, 3) a branched [4]rotaxane, 4) a bis [2]rotaxane, and 5) a novel cyclic [4]rotaxane, demonstrating, in incrementally more complex systems, the efficacy of this one-pot strategy for the construction of interlocked molecules

Dynamic combinatorial libraries of complexes with oligopyridine ligands

Chapter 1 gives a background of some achievements reached in the fields of dynamic combinatorial libraries, 2,2´-bipyridine and 2,2´:6´,2´´-terpyridine chemistry, and ferrocenes compounds in the years preceding the present work. Chapter 2 describes the study by 1H-NMR spectroscopy of the composition of different mixtures of cobalt(II) complexes with 2,2´-bipyridine and 1,10- phenanthroline ligands. Chapter 3 discusses the 1H-NMR analysis of different mixtures of complexes with different cobalt oxidation states and 2,2´-bipyridine and 1,10-phenanthroline ligands. Chapter 4 describes a new synthesis for the previously reported bpy-CH3 and bpy- CHO. The 1H-NMR spectra of their cobalt(II) complexes are discussed. It was established that the complexes in solution spontaneously formed a DCL of the fac and mer stereoisomers. Templating experiments are discussed that have the goal to change the composition of the library. Chapter 5 describes the synthesis of new 5-substituted 2,2´:6´,2´´-terpyridines and the 1H-NMR characterisation of their cobalt(II) and iron(II) complexes. Attempts to bind the complexes with different templates are discussed. Ligand exchange at one metal centre and between two different metals is also studied. Chapter 6 describes the synthesis of new 2,2´:6´,2´´-terpyridines functionalised with a ring capable of forming sandwich complexes. The 1H-NMR characterisation of their cobalt(II) and iron(II) complexes is discussed. The possibility of forming macrocycles containing two metal centres with two different complexing sites was studied. In these systems the ligand exchange could be controlled by independent actions influencing only one complex. Chapter 7 reports the detailed synthetic procedures for the products encountered and their characterisation data

Metal-directed assembly of combinatorial libraries - principles and establishment of equilibrated libraries with oligopyridine ligands

The cobalt(II) complexes [Co(bpy)(3)][PF6](2), [Co(Me(2)bpy)(3)][ PF6](2) (Me(2)bpy = 4,4` dimethyl- 2,2`-bipyridine) and [Co( phen)(3)][ PF6] (2) give paramagnetically shifted 1 H NMR spectra which may be fully assigned; the complexes are labile and ligand exchange is complete within mixing time in CD3CN solutions to give libraries of heteroleptic complexes which have been fully characterised by one- and two-dimensional (1) H NMR spectroscopy. A library comprising mer and fac isomers of [CoL3](2+) ( L = 2,2`- bipyridine-5-carbaldehyde) can be ampli. ed by speci. c reaction of the fac stereoisomer with a triamine to give a new hexadentate ligand, although other ligand exchange processes compete

Exploiting neighboring-group interactions for the self-selection of a catalytic unit

This article reports a new approach for the screening of dynamic combinatorial libraries based on the tethering of a model of the transition state of the reaction. This approach has numerous advantages for catalyst development: 1. It allows one to screen independently the catalytic and the recognition site of a catalyst (all approaches performed so far screen a catalysts on the basis of both properties with serious limitations in catalyst combinatorial space accessible); 2. It allows one to pinpoint even the most subtle catalytic effects that are often hidden by a poor binding. It is worth pointing out that without tethering strategy it would not have been able to select any catalyst