Periodic Reporting for period 4 - SUPRANET (Supramolecular Recognition in Dynamic Covalent Networks at Equilibrium and Beyond)
Berichtszeitraum: 2024-01-01 bis 2025-12-31
Most chemical reactions proceed predominantly in one direction: reactants are converted into products and the system eventually reaches a stable end state. In this sense, many reactions resemble chemical “one-way streets”. In contrast, Project SUPRANET focused on a fascinating and much less explored class of reactions that proceed in both the forward and the backward direction. Such reversible reactions form chemical “two-way streets”, enabling molecules to continuously interconvert and explore many different structures. These reversible processes are the foundation of dynamic chemical networks, in which many compounds coexist and transform into one another until the most stable or best-adapted structures emerge. Chemical “two-way streets” can operate in two conceptually different ways. First, molecules can move forward and backward along the same reaction pathway, analogous to walking along the same trail in both directions. Second, they can undergo cyclic or “round-trip” processes, where forward and backward transformations follow different routes through the reaction network. Project SUPRANET explored both types of dynamic behaviour and used them as design principles to construct adaptive supramolecular systems.
The scientific challenge addressed by the project was to harness such dynamic reaction networks to discover and control complex functional molecules. Conventional molecular design typically relies on stepwise synthesis of predetermined targets. In contrast, dynamic chemical networks allow molecules to be selected and amplified from mixtures through processes such as self-assembly, template effects, or kinetic trapping. Understanding and exploiting these processes is a central question in modern chemistry because they provide a pathway toward adaptive molecular systems resembling the behaviour of biological chemistry.
The importance of this research extends beyond fundamental science. Dynamic molecular systems underpin key biological functions such as molecular recognition, membrane transport, and the emergence of self-replication. By learning how to construct and control similar behaviour in synthetic systems, chemists can develop new strategies for sensing, drug delivery, ion transport, responsive materials, and other technologies relevant to medicine and biotechnology.
Within this context, SUPRANET pursued four overarching objectives.
First, the project aimed to identify and construct new anion and ion-pair receptors, particularly for chloride ions, using dynamic covalent self-assembly. Such receptors may ultimately contribute to strategies addressing diseases linked to dysfunctional ion transport, such as cystic fibrosis.
Second, the project sought to develop supramolecular host structures capable of kinetically trapping ions—conceptually described as molecular “prisons”—that could enable controlled transport of ions across membranes and their release under defined conditions.
Third, the project investigated network-based chemical replication processes, exploring how dynamic reaction cycles might generate self-amplifying behaviour and thereby shed light on fundamental questions about the chemical origins of life.
Fourth, the project explored fuel-driven and network-controlled self-assembly, including transient vesicle-like systems that could function as delivery platforms for molecular cargo.
The scientific challenge addressed by the project was to harness such dynamic reaction networks to discover and control complex functional molecules. Conventional molecular design typically relies on stepwise synthesis of predetermined targets. In contrast, dynamic chemical networks allow molecules to be selected and amplified from mixtures through processes such as self-assembly, template effects, or kinetic trapping. Understanding and exploiting these processes is a central question in modern chemistry because they provide a pathway toward adaptive molecular systems resembling the behaviour of biological chemistry.
The importance of this research extends beyond fundamental science. Dynamic molecular systems underpin key biological functions such as molecular recognition, membrane transport, and the emergence of self-replication. By learning how to construct and control similar behaviour in synthetic systems, chemists can develop new strategies for sensing, drug delivery, ion transport, responsive materials, and other technologies relevant to medicine and biotechnology.
Within this context, SUPRANET pursued four overarching objectives.
First, the project aimed to identify and construct new anion and ion-pair receptors, particularly for chloride ions, using dynamic covalent self-assembly. Such receptors may ultimately contribute to strategies addressing diseases linked to dysfunctional ion transport, such as cystic fibrosis.
Second, the project sought to develop supramolecular host structures capable of kinetically trapping ions—conceptually described as molecular “prisons”—that could enable controlled transport of ions across membranes and their release under defined conditions.
Third, the project investigated network-based chemical replication processes, exploring how dynamic reaction cycles might generate self-amplifying behaviour and thereby shed light on fundamental questions about the chemical origins of life.
Fourth, the project explored fuel-driven and network-controlled self-assembly, including transient vesicle-like systems that could function as delivery platforms for molecular cargo.
During the course of the project, these objectives were addressed through the development of new dynamic covalent chemistries, particularly orthoester- and related tripodal bridgeheads (thioorthoester, trialkoxysilane, trialkoxyborane), combined with supramolecular recognition and advanced analytical methods. The project established a versatile platform for the self-assembly of adaptive molecular cages and ion receptors, clarified key mechanistic principles governing their dynamic behaviour, and demonstrated how reversible reaction networks can be used to discover and control functional supramolecular systems.
A central outcome of SUPRANET was the successful development of orthoester-based bridgeheads as a general design principle for stimuli-responsive dynamic covalent host architectures. This outcome was disseminated as an Account article in a prestigious Account of Chemical Research (https://pubs.acs.org/doi/10.1021/acs.accounts.3c00738(öffnet in neuem Fenster)). A second central outcome is the successful synthesis of a minimalistic "prison" for the ion Na+ (manuscript in preparation). A third outcome, which is central to continuing research in the lab of the PI, was the creation of the first chemically fuelled non-equilibrium networks based on the dissipative exchange of P-X bonds.
In conclusion, SUPRANET showed that reversible chemical “two-way streets” provide a powerful strategy for constructing adaptive molecular systems. The project significantly advanced dynamic covalent supramolecular chemistry, produced numerous high-impact publications and conference contributions, and led to a patent application for a thioorthoester-based material capable of removing toxic metals from solution.
A central outcome of SUPRANET was the successful development of orthoester-based bridgeheads as a general design principle for stimuli-responsive dynamic covalent host architectures. This outcome was disseminated as an Account article in a prestigious Account of Chemical Research (https://pubs.acs.org/doi/10.1021/acs.accounts.3c00738(öffnet in neuem Fenster)). A second central outcome is the successful synthesis of a minimalistic "prison" for the ion Na+ (manuscript in preparation). A third outcome, which is central to continuing research in the lab of the PI, was the creation of the first chemically fuelled non-equilibrium networks based on the dissipative exchange of P-X bonds.
In conclusion, SUPRANET showed that reversible chemical “two-way streets” provide a powerful strategy for constructing adaptive molecular systems. The project significantly advanced dynamic covalent supramolecular chemistry, produced numerous high-impact publications and conference contributions, and led to a patent application for a thioorthoester-based material capable of removing toxic metals from solution.
The project led to a number of groundbreaking results. Specific "firsts" include the first dynamic covalent self-assembly templated by an ion pair, the first use of three reversible transformations in the context dynamic covalent hosts (thioorthoester, trialkoxysilane and trialkoxyborane exchange), the first orthoester-based carceplex which is also the smallest carceplex prepared to date and the first three instances of chemical fuelled P-X networks (phosphoramidates, phosphodiesters, acylphosphates).