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 language | English |
|---|---|
| Pages (from-to) | 9-14 |
| Number of pages | 6 |
| Journal | Journal of Inclusion Phenomena |
| Volume | 44 |
| Issue number | 1-4 |
| DOIs | |
| State | Published - Dec 1 2002 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Theoretical insights into the formation, structure, and energetics of some cyclodextrin complexes
AU - Bodor, Nicholas
AU - Buchwald, Peter
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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.
AB - 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.
KW - α-, β-, and y-cyclodextrin complex
KW - Deformation index
KW - Estradiol
KW - Free energy
KW - Molecular size
UR - http://www.scopus.com/inward/record.url?scp=0347026247&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347026247&partnerID=8YFLogxK
U2 - 10.1023/A:1023059016514
DO - 10.1023/A:1023059016514
M3 - Article
AN - SCOPUS:0347026247
VL - 44
SP - 9
EP - 14
JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry
JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry
SN - 1388-3127
IS - 1-4
ER -