Theoretical insights into the formation, structure, and energetics of some cyclodextrin complexes

Nicholas Bodor, Peter Buchwald

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To investigate the physicochemical aspects relevant for the formation of various cyclodextrin inclusion complexes and to search for corresponding general structure-complex-stability relationships, stability data of 1:1 complexes for 179, 310, and 51 guest molecules with unsubstituted α-, β-, and γ-cyclodextrin were collected. Statistical analysis using structure-based parameters such as molecular size, hydrophobicity, rotatable bonds, electronic properties, and the presence or absence of more than 150 various functional or structural moieties were performed. The complexation thermodynamics could be well described within the framework of our recently introduced molecular size-based model for nonassociative liquids. With increasing guest size, 1:1 complex stability, as measured by In K or ΔG0, increases linearly up to a size limit characteristic for each CD, and the corresponding slopes and intercepts are in agreement with those predicted by the model. For larger structures, values level off and are scattered around an average value depending on shape, goodness of fit, and possibly lipophilicity and some specific effects (e.g. such as those caused by presence of phenol functionality). The complexation between β-cyclodextrin and certain large steroidal guest molecules, especially a brain-targeted estradiol chemical delivery systems (E2-CDS) that is under clinical development, was investigated in details based on fully relaxed semiempirical AM1 quantum chemical calculations. A deformation index (DI) of the CD ring computed using these fully optimized host-guest geometries could be used to characterize the conformational change of the guest.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalJournal of Inclusion Phenomena
Volume44
Issue number1-4
DOIs
StatePublished - Dec 1 2002

Fingerprint

cyclodextrins
Cyclodextrins
hydrophobicity
Complexation
Molecules
Hydrophobicity
Phenol
Hydrophobic and Hydrophilic Interactions
Thermodynamics
thermodynamics
Electronic properties
goodness of fit
phenol
electronics
estradiol
Brain
Statistical methods
statistical analysis
phenols
brain

Keywords

  • α-, β-, and y-cyclodextrin complex
  • Deformation index
  • Estradiol
  • Free energy
  • Molecular size

ASJC Scopus subject areas

  • Chemistry(all)
  • Condensed Matter Physics

Cite this

Theoretical insights into the formation, structure, and energetics of some cyclodextrin complexes. / Bodor, Nicholas; Buchwald, Peter.

In: Journal of Inclusion Phenomena, Vol. 44, No. 1-4, 01.12.2002, p. 9-14.

Research output: Contribution to journalArticle

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