Per‐O‐methylated α‐ and β‐CD: Cyclodextrins with Inverse Hydrophobicity

Abstract

The investigation focuses on the computer‐aided generation of the molecular geometries, contact surfaces, and lipophilicity patterns of per‐O‐methylated α‐CD (1) and its β‐CD homolog 2, and compares them with their parent non‐substituted cyclodextrins. The molecular geometries, compared via statistical analysis of crystal structure data available, reveal 1 and 2 to be considerably more flexible than α‐and β‐CD, allowing wide variations in the tilting of the glucose units relative to the macrocyclic ring axes. The comparative evaluation of their contact surfaces not only discloses a substantial increase of the torus heights upon per‐O‐methylation (from ∼8.0Å in α‐ and β‐CD, to → 11.1Å in 1 and 2), but also an enlargement of their cavity areas by 40% (+35Å2 for α‐CD → 1) and 70% (+75Å2 for β‐CD → 2), respectively. The hydrophobic characteristics of 1 and 2, emerging from the molecular lipophilicity patterns (MLPs) generated and projected onto the contact surfaces in color‐coded from, are inverse to those for α‐ and β‐CD: the most hydrophobic surface regions of 1 and 2 are located at the torus rims made up by the 2‐OMe and 3‐OMe groups at one side, and the 6‐CH2OMe moieties at the other, with a hydrophobic „band”︁ wrapping around the outside of the macrocycles; these „exo‐lipophilic”︁ topographies are opposed by pronouncedly hydrophilic central cavities. A variety of experimental findings can be rationalized on the basis of the opposite lipophilicity profiles of the CDs and their permethylated analogs, such as for example the opposite orientation of benzaldehyde, p‐nitrophenol, and 3‐iodopropionic acid in the cavities of α‐CD and of 1. Thus, the notion is substantiated that the operation of dispersive interactions between guest and CD‐host cavities play a more dominant role in inclusion complex formation than hitherto appreciated.

Enhanced Solubilisation of Six PAHs by Three Synthetic Cyclodextrins for Remediation Applications: Molecular Modelling of the Inclusion Complexes

“…Although ANT and PHE present lengths (9.14 and 9.20 Å, respectively, Table 3 ) bigger than that of β-CD (about 7.9 Å), the fact of its high solubility increase indicates that the methyl groups of RAMEB and their arrangement permit a closer interaction with both PAHs. According to Immel and Lichtenthaler [39] , the introduction of methyl groups to O6H hydroxyl groups increases the depth of the cavity up to 10–11 Å, although the diameter of the cavity does not change. It indicates that probably only a very small part of both PAHs remains into contact with water, increasing their aqueous solubility.…”

Recombinant Cyclodextrinase fromThermococcus kodakarensisKOD1: Expression, Purification, and Enzymatic Characterization

“…All of the hydroxyl groups in CDs are oriented to the outside of the ring, while the glycosidic oxygen and two rings of nonexchangeable hydrogen atoms are directed toward the interior of the cavity. This combination provides CDs a hydrophobic inner cavity and a hydrophilic exterior [ 2 ]. The hydrophobic environment of the cavity enables CDs to form inclusion complexes with many water-insoluble compounds that have numerous useful applications in the food, pharmaceutical, drug delivery, and chemical industries as well as in agriculture and environmental engineering [ 3 ].…”

Inhibition of acid‐induced decomposition of diphenyltriazenes by complexation with cyclodextrins

“…Inclusion in the cavity of CDs certainly renders a relatively nonpolar environment, at least in comparison with water, which leads to a decrease in triazene basicity and, ultimately, in the rate of decomposition. The fact that BCD is the only host, among those used in this study, for which reactivity of the cyclodextrin-TH + complex is detected suggests guest triazenes experience lesser environmental changes upon inclusion in BCD than upon inclusion in the narrower ACD (ultimately with two host units) or in any of the BCD derivatives (in which alkyl substituents elongate the cavity and increase the hydrophobicity of its edges [20,21]). …”