Host–Guest Complexation through Geometric Self-Optimization in [12]Cycloparaphenylene

Host-guest chemistry typically relies on attractive noncovalent interactions to drive the inclusion of guest molecules within a host framework. In contrast, we demonstrate that [12]cycloparaphenylene ([12]CPP) forms inclusion complexes not through such interactions but through geometric self-optimization─a process in which the host molecule spontaneously adjusts its conformation to achieve energetic stabilization upon guest incorporation. Single-crystal X-ray structure analyses of complexes of [12]CPP with various achiral and chiral molecules revealed that guest molecules interacting negligibly with the host in solution, or those whose access to the cavity is prevented by intermolecular interaction at the outer π-surface of [12]CPP, can nevertheless be accommodated within the rigid, covalently bonded cavity of [12]CPP. Structural evaluation of the complex of [12]CPP and ethyl abietate revealed several intermediate states of geometric self-optimization, providing experimental insight into the mechanism of host-guest accommodation. This self-optimization mechanism also enables spontaneous crystallization of liquid compounds as host-guest crystals suitable for single-crystal X-ray structure analysis, allowing the determination of molecular structures and absolute configurations of liquid molecules. These findings establish geometric self-optimization as a new principle of host-guest chemistry and highlight its potential for extending molecular inclusion beyond the limits imposed by conventional attractive interactions.