Design, synthesis, and conformational dynamics of a gated molecular basket

Article abstract of DOI:10.1021/ja060534l

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 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 1_a indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 A³) is complementary in size, shape, and electrostatic potential to chloroform (74.9 A³). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C₃, axis.