Selective Host Molecules Obtained by Dynamic Adaptive Chemistry

Abstract

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry.

Mirror symmetry breaking upon spontaneous crystallization from a dynamic combinatorial library of macrocyclic imines

“…These dynamic processes involve: (a) the reversible reaction of aldehyde with amine to form the imine bond, (b) mutual interconversion of macrocyclic and linear imines, which constitute the multiproduct dynamic combinatorial library, (c) formation of imine complexes with a template, in this case Li + , which strongly favours [1+1] macrocycle 3, and (d) deposition of the complex in the form of crystals (Scheme 2). The first three stages (a)-(c) were common to DCL experiments under thermodynamic control 19 and proceeded in the solution, while the crystallization step occurred when LiCl was used as the template, breaking the ''all-in-one-phase'' paradigm of Dynamic Combinatorial Chemistry (DCC) [23][24][25] and ultimately leading to the spontaneous crystallization of 3ÁLiCl.…”

Probing secondary interactions in biomolecular recognition by dynamic combinatorial chemistry

“…DCC has recently emerged as a powerful technology for exploring the recognition modes governing biomolecular recognition. [34][35][36][37][38][39][40][41][42][43][44] DCC offers the advantage that hit generation is induced by the target itself, thereby enabling the identification of selective binders with optimal structural features for molecular recognition or compounds that would not be formed in the absence of the target. 37,44,45 DCC is a one-pot screening method involving (a) competition between components of a Dynamic Combinatorial Library (DCL) through reversible covalent bond formation, (b) targetinduced selection of the best suited components, and (c) amplification of the optimal target-binding constituent through the reorganization of the dynamic system according to Le Cha ˆtelier principle (Fig.…”

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

“…The synthesis of cryptands with C 3 symmetry by peculiar reactions (acetylenic coupling [ 16 – 18 ], CuAAC [ 19 – 22 ], double or triple bond metathesis [ 23 – 25 ], aromatic nucleophilic substitutions [ 26 – 33 ], or via the amplification of a cryptand belonging to DCC libraries [ 2 , 25 , 34 – 35 ]) allowed accessing of more sophisticated architectures. In a previous work [ 32 ] we reported the formation of a host–guest complex between a cryptand having pyridine units in the bridges and 1,3,5-triphenylbenzene caps ( 1 , Fig.…”