Strategies for Exploring Functions from Dynamic Combinatorial Libraries

Abstract

Dynamic combinatorial chemistry (DCC) is a powerful approach for creating complex chemical systems, giving access to the studies of complexity and exploration of functionality in synthetic systems. However, compared with more advanced living systems, the man‐made chemical systems are still less functional, due to their limited complexity and insufficient kinetic control. Here we start by introducing strategies to enrich the complexity of dynamic combinatorial libraries (DCLs) for exploiting unexpected functions by increasing the species of building blocks and/or templates used. Then, we discuss how dynamic isomerization of photo‐switchable molecules help DCLs increase and alter the systemic complexity in‐situ. Multi‐phase DCLs will also be reviewed to thrive complexity and functionality across the interfaces. Finally, there will be a summary and outlook about remote kinetic control in DCLs that are realized by applying exogenous physical transduction signals of stress, light, heat and ultrasound.

Sulfur in Dynamic Covalent Chemistry

“…Dynamic covalent chemistry (DCC) relies on the preparation, exploitation, and analysis of dynamic mixtures of compounds [1] . Some functions performed by DCC include drug delivery, [2] self‐replication, [3] the preparation of covalent organic frameworks [4] and materials, [5] and more [6] . The use of reversible reactions involving covalent bonds is central to the concept of DCC.…”

“…[1] Some functions performed by DCC include drug delivery, [2] self-replication, [3] the preparation of covalent organic frameworks [4] and materials, [5] and more. [6] The use of reversible reactions involving covalent bonds is central to the concept of DCC. Reversibility confers adaptability towards external changes and allows the composition to evolve until the thermodynamic equilibrium is reached, and the covalent character of the implemented chemistry provides product stability.…”

Development of “Imprint-and-Report” Dynamic Combinatorial Libraries for Differential Sensing Applications

“…24 In a dynamic combinatorial library (DCL), building blocks that form reversible covalent bonds are allowed to reach thermodynamic equilibrium, and the presence of a guest creates favorable molecular recognition events that shift this equilibrium toward host formation. 25,26 Species that are amplified in the guest-templated DCL relative to an untemplated DCL represent likely binders, which can be confirmed via receptor isolation and binding measurements. Many receptors have been identified and synthesized by this method and subsequently used by our group and others in IDAs and sensor arrays.…”

“…Dynamic combinatorial chemistry (DCC) has been applied as a promising method for both identifying and synthesizing new receptors for sensor arrays . In a dynamic combinatorial library (DCL), building blocks that form reversible covalent bonds are allowed to reach thermodynamic equilibrium, and the presence of a guest creates favorable molecular recognition events that shift this equilibrium toward host formation. , Species that are amplified in the guest-templated DCL relative to an untemplated DCL represent likely binders, which can be confirmed via receptor isolation and binding measurements. Many receptors have been identified and synthesized by this method and subsequently used by our group and others in IDAs and sensor arrays. , Nonetheless, despite addressing the challenge of identifying and synthesizing receptors, this approach still requires isolation of individual receptors and development of several IDAs.…”

Graph-based Automated Macro-Molecule Assembly

“…Besides proteins with well-defined secondary and tertiary structures, there also is the broad class of intrinsically disordered proteins − that do perform important biochemical functions, including catalysis, despite their lack of rigidity. This is taken to yet another level by dynamic combinatorial libraries − in which molecular functions (including catalysis) are achieved by only temporary association of nonbonded fragments.…”