Structural study of the inclusion compounds of thymol, carvacrol and eugenol in β-cyclodextrin by X-ray crystallography

Abstract

The crystal structures of the inclusion compounds of thymol, carvacrol and eugenol, (components of essential oils of vegetable origin) in -cyclodextrin have been determined. Thymol/-CD crystallizes in the space group P1 containing two host molecules in its asymmetric unit whereas both carvacrol/-CD and eugenol/-CD complexes crystallize in the space group C2. In all three complexes two host molecules form head-to-head dimers their guest/host stoichiometry being: 1/2 (carvacrol/-CD), 2/2 (thymol/-CD) and 3/2 (eugenol/-CD). In the cases of the thymol/-CD and the carvacrol/-CD complexes the -CD dimers are arranged according to the channel packing mode. The accommodation of the geometrical isomer guests is performed solely by their hydrophobic groups revealing the leading role of the hydrophobic driving forces in the complexation process whereas the position of their hydroxyl group affects the stoichiometry of the formed dimeric complexes. In the case of the eugenol/-CD dimeric complex one guest molecule is found lying between the -CD groups in a sandwich fashion whereas the other two symmetry related guests protrude outwards the narrower rim of the hosts with only their hydrophobic allylchain located inside the hosts' cavities. This arrangement prohibits the formation of a channel and the observed crystal packing is that of a Tetrad mode.

Optimisation of β-cyclodextrin inclusion complexes with natural antimicrobial agents: thymol, carvacrol and linalool

“…Peaks corresponding to β-CD and free thymol were also detected in the spectrum. The 1:1 mole ratio observed for the thymol/β-CD in the current study is consistent with the work of Bethanis et al (2013) who determined a 1:1 mole ratio of thymol/β-CD in the solid state using x-ray crystallography. Although the qualitative analysis using ES/MS indicates that thymol was complexed with β-CD, the results do not enable the efficiency of the process to be determined and so a quantitative analysis using GC was used to assess the IE.…”

“…x-ray crystallographic studies of Bethanis et al (2013) who reported a 1:1 mole ratio for thymol/β-CD and Ceborska (2016) who reported a 2:2 molar ratio for the (-)-linalool/β-CD dimer. It is interesting to note, however, that the X-ray crystallographic study by Bethanis et al (2013) suggests that a 1:2 carvacrol/β-CD ratio exists in the solid state where the complex was produced using a guest/host molar ratio of 1.5:1. Under the synthesis conditions used in the current work, if a complex was formed having a 1:2 mole ratio of guest/host then that would result in an observed IE of only 50% (w/w) so clearly a 1:2 complex was not obtained in the present study.…”

Encapsulation of carvacrol, a monoterpene present in the essential oil of oregano, with β-cyclodextrin, improves the pharmacological response on cancer pain experimental protocols

“…Bethanis et al [39] and Mulinacci et al [40] demonstrated through different methods that the CARV is found fully immersed inside the hydrophobic cavity of b-CD. This complex, when prepared with the co-precipitation method in aqueous solution, gives a complex monomer of 1/1 stoichiometry, in which the isopropyl group of the CARV is located closer to the larger side of the hydrophobic cavity of b-CD.…”

Functionalization and characterization of cotton with phase change materials and thyme oil encapsulated in beta-cyclodextrins

“…Thyme oil, composed of thymol (44.88%) and carvacrol (4.6%), was applied to MCT-CDfabrics in defined conditions to prevent evaporation of the label components. The oil application was made with the assumption that β-CD can encapsulate carvacrol and thymol [34,[50][51][52]. In fact, the interaction of β-CD and carvacrol in aqueous solution, results in a 1:1 complex, in which the isopropyl group of the molecule is located closer to the larger side of the hydrophobic cavity of β-CD.…”