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 H-1 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 Delta delta/delta T coefficients of 17.0, 17.3, and 4.7 ppb K-1, respectively. In combination with the results from variable temperature H-1 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 1(a) as the most favorable conformation, with three additional conformers, 1(b), 1(c), and 1(d), 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 1(a). 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 la indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 A(3)) is complementary in size, shape, and electrostatic potential to chloroform (74.9 A(3)). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C axis.