Dynamic combinatorial/covalent chemistry: a tool to read, generate and modulate the bioactivity of compounds and compound mixtures

Abstract

Reversible covalent bond formation under thermodynamic control adds reactivity to self-assembled supramolecular systems, and is therefore an ideal tool to assess complexity of chemical and biological systems. Dynamic combinatorial/covalent chemistry (DCC) has been used to read structural information by selectively assembling receptors with the optimum molecular fit around a given template from a mixture of reversibly reacting building blocks. This technique allows access to efficient sensing devices and the generation of new biomolecules, such as small molecule receptor binders for drug discovery, but also larger biomimetic polymers and macromolecules with particular three-dimensional structural architectures. Adding a kinetic factor to a thermodynamically controlled equilibrium results in dynamic resolution and in self-sorting and self-replicating systems, all of which are of major importance in biological systems. Furthermore, the temporary modification of bioactive compounds by reversible combinatorial/covalent derivatisation allows control of their release and facilitates their transport across amphiphilic self-assembled systems such as artificial membranes or cell walls. The goal of this review is to give a conceptual overview of how the impact of DCC on supramolecular assemblies at different levels can allow us to understand, predict and modulate the complexity of biological systems.

An “Ingredients” Approach to Functional Self‐Synthesizing Materials: A Metal‐Ion‐Selective, Multi‐Responsive, Self‐Assembled Hydrogel

“…By designing a building block to contain the right ingredients, a multi-responsive, self-assembled hydrogel was obtained through a process of template-induced self-synthesis in a dynamic combinatorial library. The system can be switched between gel and solution by light, redox reactions, pH, temperature, mechanical energy and sequestration or addition of Mg II salt.Recent developments in dynamic combinatorial chemistry [1] have led to the new concept of self-synthesizing materials, [2] in which a self-assembly process drives the synthesis of the very molecules that self-assemble from a mixture of interconverting species. For cases in which self-assembly is based on non-covalent interactions, self-synthesis involves the formation of covalent bonds.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…It is also worthy to note that lipase-catalyzed reactions have been used in "dynamic systemic resolutions" (DSR) (Herrmann, 2014;Sakulsombat et al, 2012b) of hemithioacetals (Zhang and Ramström, 2014), nitroalcohols (Vongvilai et al, 2007;Zhang et al, 2014b) and aminotriles (Vongvilai and Ramström, 2009), a process in which a dynamic system under thermodynamic control, consisting of compounds generated from reversible reactions, is coupled to an irreversible kinetically controlled reaction, thus resulting in re-equilibration of the system and amplification of the optimally reacting species. This technique cannot only lead to optically active products but is also useful for evaluating the enzyme specificities.…”

A reversible fluorescence chemosensor for sequentially quantitative monitoring copper and sulfide in living cells

“…[1][2][3][4][5][6][7]. Keeping the integrity and balance of these species would be of vital importance for physiological and pathological processes.…”