Design, Synthesis, and Conformational Dynamics of a Gated Molecular Basket

We have developed a synthesis and examined the conformational behavior and recognition
properties of dynamic molecular containers 1−3. As follows from the 1H NMR dilution, diffusion NMR, and
vapor pressure osmometry measurements, compound 1 has a low affinity for intermolecular aggregation
and is mostly present in monomeric form in dilute chloroform solutions. Inspecting the O−H chemical shift
resonances of 1, 3, and model compound 4 as a function of temperature afforded the Δδ/ΔT coefficients
of 17.0, 17.3, and 4.7 ppb K-1, respectively. In combination with the results from variable temperature 1H
NMR and IR measurements, the existence of conformers of 1 and 3 in equilibrium, each having a different
extent of hydrogen bonding, was confirmed. Molecular mechanics calculations suggested 1a as the most
favorable conformation, with three additional conformers, 1b, 1c, and 1d, populating local energy minima.
Further optimization of each of the four conformers using semiempirical PM3 and ab initio (HF/6-31G*)
methods allowed a determination of their relative free energies and the corresponding Boltzmann population
distributions which were heavily weighted toward 1a. A computed composite IR spectrum of a fraction-weighted mixture of the conformers of 1 reproduced the experimentally observed IR spectrum in its structural
features, leading to a conclusion that conformer 1aindeed dominates the equilibrium. The egg-shaped
cavity of 1 (136.6 A3) is complementary in size, shape, and electrostatic potential to chloroform (74.9 Å3).
A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand
along its C3 axis.