Variation of Cyclodextrin (CD) Complexation with Biogenic Amine Tyramine: Pseudopolymorphs of β-CD Inclusion vs. α-CD Exclusion, Deep Atomistic Insights.

Tyramine (TRM) is a biogenic catecholamine neurotransmitter, which can trigger migraines and hypertension. TRM accumulated in foods is reduced and detected using additive cyclodextrins (CDs) while their association characteristics remain unclear. Here, single-crystal X-ray diffraction and density functional theory (DFT) calculation have been performed, demonstrating the elusive pseudopolymorphs in β-CD inclusion complexes with TRM base/HCl, β-CD·0.5TRM·7.6HO () and β-CD·TRM HCl·4HO () and the rare α-CD·0.5(TRM HCl)·10HO () exclusion complex. Both and share the common inclusion mode with similar TRM structures in the round and elliptical β-CD cavities, belong to the monoclinic space group 2, and have similar herringbone packing structures. Furthermore, differs from , as the smaller twofold symmetry-related, round α-CD prefers an exclusion complex with the twofold disordered TRM-H sites. In the orthorhombic 222 lattice, α-CDs are packed in a channel-type structure, where the column-like cavity is occupied by disordered water sites. DFT results indicate that β-CD remains elliptical to suitably accommodate TRM, yielding an energetically favorable inclusion complex, which is significantly contributed by the β-CD deformation, and the inclusion complex of α-CD with the TRM aminoethyl side chain is also energetically favorable compared to the exclusion mode. This study suggests the CD implications for food safety and drug/bioactive formulation and delivery.