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 beta-cyclodextrin (beta-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 beta-cyclodextrin-chlorogenic acid-water (2/2/17), 2C(42)H(70)O(35)center dot 2C(16)H(18)O(9)center dot 17H(2)O, reveals that CGA threads through beta-CD and assembles via O-H center dot center dot center dot O hydrogen bonds and parallel-displaced pi-pi 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 beta-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 beta-CD-CGA inclusion complexes, that is, beta-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 beta-CD-CGA complex, with the CFA moiety totally enclosed in the beta-CD dimeric cavity.