Cisapride/β-cyclodextrin complexation: stability constants, thermodynamics, and guest–host interactions probed by 1H-NMR and molecular modeling studies

Autor: M. M. Al Omari, J. Eric D. Davies, Adnan A. Badwan, Mohammad B. Zughul
Rok vydání: 2007
Předmět:
Zdroj: Journal of Inclusion Phenomena and Macrocyclic Chemistry. 57:511-517
ISSN: 1573-1111
0923-0750
DOI: 10.1007/s10847-006-9242-7
Popis: Phase solubility techniques were used to obtain the complexation parameters of cisapride (Cisp) with β-cyclodextrin (β-CD) in aqueous 0.05 M citrate buffer solutions. From the UV absorption spectra and the pH solubility profile, two basic pK as were estimated: pK a(1+) = 8.7 and pK a(2+) {\hbox{0}})$$ . The results show that the hydrophobic character of Cisp contributes about 35% of the total driving force to 1:1 complex formation (slope = −0.35), while other factors, including specific interactions, contribute −10.6 kJ/mol (intercept). Protonated 1:1 Cisp/β-CD complex formation at pH 6.0 is driven by favorable enthalpy (ΔH° = −9 kJ/mol) and entropy (ΔS° = 51 J/mol K) changes. In contrast, inherent Cisp solubility is impeded by unfavorable enthalpy (ΔH° = 12 kJ/mol) and entropy (ΔS° = 90 J/mol K) changes. 1H-NMR spectra in D2O and molecular mechanical studies indicate the formation of inclusion complexes. The dominant driving force for neutral Cisp/β-CD complexation in vacuo was predominantly van der Waals with very little electrostatic contribution.
Databáze: OpenAIRE
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