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Supramolecular Recognition in Dynamic Covalent Networks at Equilibrium and Beyond

Periodic Reporting for period 2 - SUPRANET (Supramolecular Recognition in Dynamic Covalent Networks at Equilibrium and Beyond)

Reporting period: 2021-01-01 to 2022-06-30

It is a curious fact that most chemical reactions proceed only in the forward direction and can therefore be seen as the chemical equivalent of a “one-way street”. Project SUPRANET explores the fascinating world of chemical reactions that proceed in both the forward and the backward direction and therefore resemble “two-way streets”. Such chemical “two-way streets” can operate in two fundamental ways that every passionate hiker (or walker) is familiar with: first, there is the possibility to go forward and backward following the same path and second, there is the “roundtrip”, in which one travels backward along a different route. Both these types of chemical reactions are explored and applied in project SUPRANET.

So, why are these chemical “two way streets” of interest, also outside the chemical laboratory? Most importantly, carrying out “two-way street” reactions on different chemicals in the same pot is an excellent way to generate complex mixtures of interacting compounds. In project SUPRANET we use these dynamic chemical networks to achieve a number of important outcomes: first, we aim to use the approach to identify new receptors for chloride ions, which is a promising way to combat the hereditary disease cystic fibrosis. Second, we aim to use dynamic chemical mixtures to develop “prisons” for simple ions, such that these can be transported across (cell) membranes and released at will to tackle a wide range of medicinal disorders. Third, we aim to contribute to arguably the biggest open question of chemistry: how (on earth) was it possible that chemical mixtures developed the capability to make copies of themselves? Spoiler alert: we think that the “roundtrip” type of a chemical “two-way street” could have been involved. And fourth, we aim to use our network- and fuel-driven approach to develop vesicle- and nanolipid-based delivery systems, much like those used for the cellular delivery of BioNTech’s mRNA vaccines.
At this point of the overall project period, we have already achieved a number of important milestones such as the synthesis of biodegradable cages for the binding and release of the chloride ion, the exploration of two new binding motifs for anions, the dissociation of the ion pair in a simple inorganic salt (CsCl) using our network approach, the discovery of a new type of “roundtrip” reaction based on phosphoramidates and the fuel-driven generation of RNA-based vesicles.
In the remaining time of the project period, we will focus our attention on the outstanding project aims and follow up on unexpected results that were observed during the past year. Such activities will include membrane-transport studies for chloride ions, new strategies for the synthesis and use of “ion prisons”, the realization of further RNA-based “roundtrip” reactions as well as activities that bring different architectures and concepts of this project together.