With an International Collaborations in Chemistry (ICC) award, Professors Laura Gagliardi (PI) and Christopher J. Cramer (co-PI) of the University of Minnesota, supported jointly by the Macromolecular, Supramolecular, and Nanochemistry (MSN) Program and the Chemical Theory, Models and Computational Methods Program (CTMCM) in the Division of Chemistry as well as the NSF Office of International Science and Engineering (OISE), will engage in research with Professor Jonathan Nitschke of the Department of Chemistry, Cambridge University, United Kingdom, to assess the fundamental factors affecting binding and recognition in the aqueous host-guest chemistry of small to moderate-sized organic molecules inside self-assembling, metal-templated cages. By taking advantage of spiral feedback between modeling and experiment, they will identify key steric and electrostatic interactions in the complexes, the control of which will facilitate the rational design of improved host-guest combinations. Theoretical models based on both quantum and molecular mechanics will be employed. Quantum mechanical models will be employed to supplement experiment with benchmark data for the selection of classical mechanical force fields and also be used to compute spectral data (e.g., NMR and UV/Vis) in order to compare to experimental host-guest combinations. Classical mechanical force field modeling will be used to simulate the dynamical behavior of host-guest combinations and for the prediction of potentials of mean force associated with aqueous binding events. With sufficient validating data in hand, in silico design efforts will be undertaken with the goal of focusing synthetic efforts on host-guest combinations showing enhanced selectivity and binding efficiencies.
Molecular cages have been shown to stabilize unstable molecules, such as white phosphorus, a spontaneously-flammable and highly toxic form of the element. Cages can also selectively speed up (catalyze) reactions by binding to high-energy reactive intermediates, thus lowering their energies. In order to extend these uses and develop new ones, fundamental understanding must be gained as to the weak interactions between encapsulated molecules and their hosts. This collaborative research project will allow a US-UK team to combine theory and experiment to come to an understanding of the fundamentals of this 'host-guest chemistry' with the goal of being able to design new cages for applications as yet undreamt-of.