An iterative approach using simulations and experiments for the investigation of supramolecular dynamics of cucurbit[n]uril multicomponent host–guest systems

• Applicant: Dr. Tim Kohlmann
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554475391

The entire world is based on complexity, on intertwined interactions of different chemical molecules in systems that require a constant supply of energy. Much of the complexity observed in nature is based on supramolecular chemistry (that is, the species are held together by intramolecular forces), where a variety of structures with versatile dynamic transformations are possible. As a system in this project, host-guest complexes with cucurbit[n]urils (CB[n]) as hosts will be investigated. The aim is to develop an approach in which simulations of the kinetics of the system defines the possible structures of guests that are likely to lead to a pre-defined targeted outcome. The simulations are followed by experiments to determine if the desired function can be achieved. The simulations will determine the parameter space, which are the concentrations of hosts and guests, rate and equilibrium constants, and the time of addition of the system’s components, that will lead to the targeted outcome. The formation of guest complexes will be determined by fluorescence studies while the kinetics will be studied by stopped-flow. In complex systems with multiple competitive reaction pathways the properties of the system cannot be predicted from the parameters (rate and equilibrium constants) known for pairwise interactions. The initial targeted outcome is to implement a system that can be kept under kinetic control. A ditopic guest will be used where the naphthyl moiety will bind to CB[7], while the alkyl ammonium moiety will bind to CB[6], and the these two moieties are separated by two spacers with different length. The competitive pathways will be the irreversible formation of the CB[6] complex while the reversible fast complexation to CB[7] will provide the kinetic trap. Once the CB[6]/CB[7] system has been implemented studies will be done with the larger CB[8] macrocycle to test the robustness of the simulation/experimental methodology and to expand on the types of competitive pathways that will be studied since CB[8] readily forms complexes with two organic guest molecules. The impact of this work will be to implement a simulation/experimentation methodology which will rapidly screen if a specific guest is suitable to achieve a pre-defined outcome for a supramolecular system. The proposed work will also lead to mechanistic insights on how to build and control the outcomes of supramolecular systems which contain competitive pathways and increased complexity.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professorin Dr. Cornelia Bohne