Solid-State Conformational Flexibility at Work: Energetic Landscape of a Single Crystal-to-Single Crystal Transformation in a Cyclic Hexapeptoid

We describe the energetic landscape beyond the solidstate dynamic behavior of a cyclic hexapeptoid decorated with four propargyl and two methoxyethyl side chains, namely, cyclo-(Nme-Npa(2))(2), Nme = N-(methoxyethyl)glycine, Npa = N-(propargyl)glycine. By increasing the temperature above 40 degrees C, the acetonitrile solvate form 1A starts to release acetonitrile molecules and undergoes a reversible single crystal-to-single crystal transformation into crystal form 1B with a remarkable conformational change in the macrocycle: two propargyl side chains move by 113 degrees to form an unprecedented CH-pi zipper. Then, upon acetonitrile adsorption, the CH-pi zipper opens and the crystal form 1B transforms back to 1A. By conformational energy and lattice energy calculations, we demonstrate that the dramatic side-chain movement is a peculiar feature of the solid-state assembly and is determined by a backbone conformational change that leads to stabilizing CH center dot center dot center dot OC backbone-to-backbone interactions tightening the framework upon acetonitrile release. Weak interactions as CH center dot center dot center dot OC and CH-pi bonds with the guest molecules are able to reverse the transformation, providing the energy contribution to unzip the framework. We believe that the underlined mechanism could be used as a model system to understand how external stimuli (as temperature, humidity, or volatile compounds) could determine conformational changes in the solid state.

Automated summary

The study reveals a reversible single crystal-to-single crystal transformation in a cyclic hexapeptoid upon heating, resulting in significant side-chain movement and conformational changes with the formation of unique CH-pi bonds. Upon acetonitrile adsorption, the changes are reversed back to the original structure.