Hydroxypropyl-Substituted β-Cyclodextrins: Influence of Degree of Substitution on the Thermodynamics of Complexation with Tauroconjugated and Glycoconjugated Bile Salts

Abstract

The effect of the degree of substitution (DS) on the ability of hydroxypropylated β-cyclodextrin (HPβCD) to form inclusion complexes with six different bile salts, found within the intestinal tracts of rats, dogs, and humans, was studied by isothermal titration calorimetry. The composition and molecular structure of the cyclodextrin samples were characterized by MALDI-TOF mass spectrometry together with 1D and 2D-NMR, and some of the complexes were studied by 2D ROESY NMR. The stability and structure of the complexes were mainly determined by the position of hydroxyl groups on the bile salts and depended relatively little on the number of hydroxypropyl side chains on the CDs. The enthalpy and entropy of complexation exhibited a strong linear increase as the DS increased from 0 to 1, and a pronounced enthalpy-entropy compensation was observed. These observations are interpreted as an increased release of ordered water from the hydration shells of the bile salts, caused by the hydroxypropyl substituents on the rim of the CD. It is estimated that each CD hydroxypropyl substituent dehydrates a hydrophobic surface area of approximately 10 Å(2).

Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether‐β‐cyclodextrin

“…Generally, the stability constants are lower than the values reported for natural βCD (∼30%) , slightly lower than methylated βCD with a degree of substitution of 0.52 and at the approximately same level as the values obtained for the interaction with hydroxypropyl‐βCD with a degree of substitution of 0.5–0.65 . Using isothermal titration calorimetry, Schönbeck et al have recently reported decreasing stability constants for tauro‐ and glyco‐conjugated bile salts with hydroxypropyl‐βCD when the degree of substitution is increased from 0.54 to 1.06, whereas the opposite was reported by Zia et al for testosterones interacting with SBEβCD. When comparing the TCDC‐ and TC‐SBEβCD stability constants obtained in the current study to the corresponding data for complexation with hydroxypropyl‐βCD, degree of substitution on 1.0 , it is clear that the stability constants are higher for the interaction with SBEβCD.…”

“…Using isothermal titration calorimetry, Schönbeck et al have recently reported decreasing stability constants for tauro‐ and glyco‐conjugated bile salts with hydroxypropyl‐βCD when the degree of substitution is increased from 0.54 to 1.06, whereas the opposite was reported by Zia et al for testosterones interacting with SBEβCD. When comparing the TCDC‐ and TC‐SBEβCD stability constants obtained in the current study to the corresponding data for complexation with hydroxypropyl‐βCD, degree of substitution on 1.0 , it is clear that the stability constants are higher for the interaction with SBEβCD. The difference in the flexibility, the size, and the polarity of the two substitutions may hold some of the explanation for this observation.…”

Thermodynamic investigation of the interaction between cyclodextrins and preservatives — Application and verification in a mathematical model to determine the needed preservative surplus in aqueous cyclodextrin formulations

“…The degree of substitution and its effect on the stability constant for complexes with modified βCDs has previously been investigated in several studies and shown to be highly influenced by the guest molecule (e.g. Schönbeck et al, 2010Schönbeck et al, , 2011Yuan et al, 2008; Buvári-Barcza and Barcza, 1999). The substituents on the CDs are in general considered to extent the cavity, which increases the hydrophobic interactions between the hydrophobic part of the small guest molecule protruding the cavity and the substituent causing a stronger binding (Yuan et al, 2008;Buvári-Barcza and Barcza, 1999).…”

Thermodynamics of Resulting Complexes Between Cyclodextrins and Bile Salts

“…Among the numerous guests researched, bile salts attracted much more attention because they are one kind of important surfactant-like biological amphipathic compounds possessing a steroid skeleton, which have distinctive detergent properties and play an important role in the metabolism and excretion of cholesterol in mammals [6]. For example: the thermodynamics and structure of inclusion compounds of glyco-and tauro-conjugated bile salts with CDs and their derivatives have been studied by Holm et al during the last years [7][8][9][10][11]; the interactions of different kinds of bile salts with -CD dimers linked through their secondary faces have been investigated by Reinhoudt and Vargas-Berenguel et al [12][13][14]. It has been demonstrated that the formation of inclusion complexes between CDs and guest molecules is cooperatively governed by several weak forces, such as van der Waals interactions, hydrophobic interactions, hydrogen bonding, electrostatic interactions, and every weak force does its contribution to the complexation.…”