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Per‐O‐methylated α‐ and β‐CD: Cyclodextrins with Inverse Hydrophobicity
Author(s) -
Immel Stefan,
Lichtenthaler Frieder W.
Publication year - 1996
Publication title -
starch ‐ stärke
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.62
H-Index - 82
eISSN - 1521-379X
pISSN - 0038-9056
DOI - 10.1002/star.19960480606
Subject(s) - lipophilicity , chemistry , stereochemistry , torus , ring (chemistry) , crystallography , molecular dynamics , computational chemistry , geometry , organic chemistry , mathematics
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% (+35Å 2 for α‐CD → 1 ) and 70% (+75Å 2 for β‐CD → 2 ), respectively. The hydrophobic characteristics of 1 and 2 , emerging from the molecular l ipophilicity p atterns (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‐CH 2 OMe 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.