CONTROLLING THE FREQUENCY OF MACROCYCLIC RING ROTATION IN BENZYLIC AMIDE [2]CATENANES

A combination of variable-temperature H-1 NMR spectroscopy and molecul ar mechanics calculations have been used to probe the factors that det ermine the rate of macrocyclic ring rotation in benzylic amide [2]cate nanes. The results show that the interlocked macrocycle dynamics are g overned by a delicate combination of steric effects, intricate inter-m acrocyclic arrays of hydrogen bonds, pi-pi stacking, and T herringbone -type interactions. A cascade of hydrogen-bond ruptures and formations is the principal event during circumvolution (complete rotation of on e macrocyclic ring about the other) but is accompanied by a series of cooperative conformational and co-conformational rearrangements that h elp to stabilize the energy of the molecule. The experimental picture is consistent both when activation energies are measured from the coal escence of NMR signals and when rate constants are directly measured b y spin polarization transfer by selective inversion recovery (SPT-SIR) methods. The nature of the circumrotational process means that the pr ecise structure of the diacylaromatic units has a tremendous effect on the frequency of macrocyclic ring rotation: a 2,5-thiophene-based cat enane rotates 3.2 million-fold faster than the analogous 2,6-pyridine- based system at room temperature! The polarity of the environment also plays a crucial role in determining the inter-ring dynamics: reducing the strength of the ground-state hydrogen-bonding network by employin g hydrogen bond-disrupting solvents (methanol, DMSO) increases the rat e of rotation by lowering the activation energy for circumvolution (no rmally in the region of 11-20 kcal mol(-1)) by up to 3.2 kcal mol(-1). This allows exquisite control over the kinetics of the translational behavior of the individual components of an interlocked molecular syst em, a key requirement for their development as nanoscale shuttles, swi tches, and information storage systems.