Sulfur in Dynamic Covalent Chemistry.

Sulfur has been important in dynamic covalent chemistry (DCC) since the beginning of the field. Mainly as part of disulfides and thioesters, dynamic sulfur-based bonds (DSBs) have a leading role in several remarkable reactions. Part of this success is due to the almost ideal properties of DSBs for the preparation of dynamic covalent systems, including high reactivity and good reversibility under mild aqueous conditions, the possibility of exploiting supramolecular interactions, access to isolable structures, and easy experimental control to turn the reaction on/off. DCC is currently witnessing an increase in the importance of DSBs. The chemical flexibility offered by DSBs opens the door to multiple applications. This Review presents an overview of all the DSBs used in DCC, their applications, and remarks on the interesting properties that they confer on dynamic chemical systems, especially those containing several DSBs.

Engineering multilayer chemical networks.

Dynamic multilevel systems emerged in the last few years as new platforms to study thermodynamic systems. In this work, unprecedented fully communicated three-level systems are studied. First, different conditions were screened to selectively activate thiol/dithioacetal, thiol/thioester, and thiol/disulfide exchanges, individually or in pairs. Some of those conditions were applied, sequentially, to build multilayer dynamic systems wherein information, in the form of relative amounts of building blocks, can be directionally transmitted between different exchange pools. As far as we know, this is the first report of one synthetic dynamic chemical system where relationships between layers can be changed through network operations.

Molecular Networks in Dynamic Multilevel Systems.

Dynamic multilevel systems can be assembled from molecular building blocks through two or more reversible reactions that form covalent bonds. Molecular networks of dynamic multilevel systems can exhibit different connectivities between nodes. The design and creation of molecular networks in multilevel systems require control of the crossed reactivity of the functional groups (how to connect nodes) and the conditions of the reactions (when to connect nodes). In recent years, the combination of orthogonal and communicating reactions, which can be simultaneous or individually activated, has produced a variety of systems that have given rise to macrocycles and cages, as well as molecular motors and multicomponent architectures on surfaces. A given set of reactions can lead to systems with unique responsiveness, compositions, and functions as a result of the relative reactivities. In this Concept article, different molecular networks from synthetic systems that can be produced by combinations of different reaction types are discussed. Moreover, applications of this chemistry are highlighted, and future perspectives are envisioned.

Rewiring Chemical Networks Based on Dynamic Dithioacetal and Disulfide Bonds.

The control of the connectivity between nodes of synthetic networks is still largely unexplored. To address this point we take advantage of a simple dynamic chemical system with two exchange levels that are mutually connected and can be activated simultaneously or sequentially. Dithioacetals and disulfides can be exchanged simultaneously under UV light in the presence of a sensitizer. Crossover reactions between both exchange processes produce a fully connected chemical network. On the other hand, the use of acid, base or UV light connects different nodes allowing network rewiring.

Host Amplification in a Dithioacetal-Based Dynamic Covalent Library.

Molecular amplification in a dithioacetal-based dynamic library is described for the first time. The homatropine induced selection, amplification, and isolation of one cyclophane host demonstrates the utility of dithioacetal exchange for preparing responsive dynamic libraries. Nuclear magnetic resonance and isothermal titration calorimetry analysis suggest that the amplified macrocycle forms a 1:1 complex with the template. This is the first report about a host/guest system involving a dithioacetal cyclophane.

Dithioacetal Exchange: A New Reversible Reaction for Dynamic Combinatorial Chemistry.

Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks.

Two-stage amplification of receptors using a multilevel orthogonal/simultaneous dynamic combinatorial library.

Sequential activation of different reversible exchange reactions in a dynamic combinatorial library allows directed exploration of the chemical space: initially a macrocyclic scaffold is selected by the template and finally side chain and conformational constrains are introduced into such a scaffold.

Supramolecular interactions between library members modulate the behavior of dynamic combinatorial libraries.

The presence of a supramolecular network of interactions between library members can lead to very different responses when libraries with identical molecular composition are exposed to the same template. Numerical simulations demonstrate that supramolecular interactions between library members of covalent dynamic combinatorial libraries (DCLs) can affect both degree and selectivity of the response of the library when a template molecule is added.

Covalent double level dynamic combinatorial libraries: selectively addressable exchange processes.

Hydrazones and disulfides have been combined in one dynamic system: hydrazones were exchanged by acid catalysis in the presence of disulfide and a thiol group without interference; neutralization of the reaction medium turns off the exchange of hydrazones and, at the same time, activates thiolate-disulfide exchange.