Inclusion complex of β-cyclodextrin with coffee chlorogenic acid: new insights from a combined crystallographic and theoretical study.

This work reports the elusive structural evidence for the [4]pseudorotaxane of β-cyclodextrin (β-CD) with coffee chlorogenic acid (CGA), a conjugate of caffeic acid (CFA) and quinic acid (QNA). A single-crystal X-ray structure analysis of the inclusion complex β-cyclodextrin-chlorogenic acid-water (2/2/17), 2CHO·2CHO·17HO, reveals that CGA threads through β-CD and assembles via O-H...O hydrogen bonds and parallel-displaced π-π interactions in the twofold symmetry-related dimer yielding a [4]pseudorotaxane, which is crystallographically observed for the first time in CD inclusion complexes. The encapsulation of the aromatic ring and C=C-C(=O)O chain in the β-CD dimeric cavity indicates that the CFA moiety plays a determinant role in complexation. This is in agreement with the DFT-derived relative thermodynamic stabilities of the trimodal β-CD-CGA inclusion complexes, that is, β-CD complexed with different CGA components: C=C-C(=O)O chain > cyclohexane ring > aromatic ring. The complexation stability is further enhanced in the dimeric β-CD-CGA complex, with the CFA moiety totally enclosed in the β-CD dimeric cavity.