An Investigation into the Effects of Gating in Artificial Host Systems

The translocation of molecules in natural systems is often regulated by modulation of dynamic moieties in a process referred to as gating. In the enzyme acetylcholinesterase, the tunnel leading to the active site is regulated by five freely-rotating aromatic residues which serve as gates. Although the passageway is effectively closed off by the gates roughly 98% of any given time, the rate of guest uptake is only decreased by a factor of two. Additionally, the gates constrict the effective aperature guests must squeeze through in order to pass and thus, through the process of gating, acetylcholinesterase achieves a high degree of kinetic selectivity with only a small sacrifice of catalytic efficiency.;With the goal of incorporating gating into artificial host molecules, the Badjic group has designed and synthesized a series of molecules, termed molecular baskets, that consist of a bowl-shaped cavity with dynamic appendages (gates) tethered to the rim. In previous work within the Badjic group, phenol-based gates were shown to effectively close the basket, but the dynamics of the gates prevented an effective preorganized cavity to form and any resulting host-guest complex did not exist within a reasonable time-frame to allow study.;In an effort to more effectively close the basket and reduce gate dynamics, molecular baskets containing pyridyl gates were synthesized and their properties were analyzed after folding with Cu(I). The resulting basket, however, only encapsulated linear coordinating guest molecules, which prevented the study of its gating properties.;Subsequently, a basket containing pyridylamido gates was synthesized and found to form a wider variety of host guest complexes. This basket was also found to incorporate gating successfully: the entrance and departure of guest molecules are primarily dependent on the rate by which the gates fold/unfold. By modifying the structure of the gates, it was found that the rates of guest ingress and egress can be controlled and tailored.;Through the use of linear free energy relationships between the activation energies for guest entrance and departure and the thermodynamic stability of the resulting host-guest complex, it was found that the baskets displayed kinetic selectivity toward the size/shape of guest molecules: small molecules enter and leave at rates faster than larger molecules. To probe the relationship between the gate dynamics and kinetic selectivity, the experiment was repeated with molecular baskets possessing faster and slower gates. Interestingly, a correlation was found whereby faster gate dynamics resulted in increased kinetic selectivity.;In addition to gating, other interesting properties were found for the pyridylamido molecular baskets. Surprisingly, cyclohexane was found to interconvert between its two chair forms at a faster rate within the cavity than outside in the bulk solvent due to favorable interactions between the host and half-chair transition state. The baskets were also found to effectively reversibly interconvert between the metal-chelation and intramolecular hydrogen bond modes of folding with an added stimulus. By studying gating in artificial host systems, unique features such as rate control and increased kinetic selectivity can potentially be incorporated into the next generation of supramolecular catalysts.