Long-Range Effects on the Capture and Release of a Chiral Guest by a Helical Molecular Capsule

Helically folded molecular capsules based on oligoamide
sequences
of aromatic amino acids which are capable of binding tartaric acid
in organic solvents with high affinity and diastereoselectivity have
been synthesized, and their structures and binding properties investigated
by 1H NMR, X-ray crystallography, circular dichroism, and
molecular modeling. We found that elongating the helices at their
extremities by adding monomers remote from the tartaric binding site
results in a strong increase of the overall helix stability, but it
does not influence the host–guest complex stability. The effect
of this elongation on the binding and release rates of the guest molecules
follows an unexpected non-monotonous trend. Three independent observations
(direct monitoring of exchange over time, 2D-EXSY NMR, and molecular
modeling) concur and show that guest exchange rates tend to first
increase upon increasing helix length and then decrease when helix
length is increased further. This investigation thus reveals the complex
effects of adding monomers in a helically folded sequence on a binding
event that occurs at a remote site and sheds light on possible binding
and release mechanisms.