Potentiometric Study of Molecular Complexes of Weak Acids and Bases Applied to Complexes of α-Cyclodextrin with para -Substituted Benzoic Acids

Connors, Kenneth A.; Lin, Shu-Fen; Wong, Albert B.

doi:10.1002/jps.2600710220

Cited by 77 publications

(36 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Different stoichiometric ratios between ligands and CyDs, such as 1:2, 2:1, and 2:2, have been presented, but by far the most common ratio has shown to be 1:1. [49][50][51][52][53] The stoichiometric ratios that we observed from the binding patterns fell within the range of 0.9-1.1:1. This clearly indicates that the majority of the inclusion complexes had a 1:1 stoichiometry of bile salts and CyDs.…”

Section: Resultsmentioning

confidence: 90%

Characterization of Bile Salt/Cyclodextrin Interactions Using Isothermal Titration Calorimetry

et al. 2001

View full text Add to dashboard Cite

The interactions of cholate, deoxycholate, glycocholate, and taurocholate with methyl--cyclodextrin and 2-hydroxypropyl--cyclodextrin were studied by means of isothermal titration calorimetry and molecular modeling. The binding constants, standard molar enthalpy, Gibbs free energy, and entropy changes were determined for the formation of bile salt/cyclodextrin inclusion complexes. We observed a 1:1 stoichiometry for all inclusion complexes and could demonstrate marked differences in binding affinity between the different bile salt and cyclodextrin molecules. The dihydroxy bile salt deoxycholate showed significantly higher affinity toward methyl--cyclodextrin (K ) 6276 ( 164 M -1 ) and 2-hydroxypropyl--cyclodextrin (K ) 4429 ( 34 M -1 ) compared to the trihydroxy bile salt cholate (K ) 2693 ( 25 M -1 and K ) 2510 ( 98 M -1 , respectively). The conjugation of cholate with glycine or taurine lowered its affinity markedly toward methyl--cyclodextrin (K ) 1958 ( 178 M -1 and K ) 2148 ( 33 M -1 , respectively). Our molecular modeling and docking data suggest that the most probable mode of binding would be by insertion of the bile salt A-ring into the rim of the cyclodextrin containing the secondary alcohol moieties. Our results show that bile salt binding to cyclodextrin is influenced both by the degree of bile salt hydroxylation and by bile salt conjugation.

show abstract

Section: Resultsmentioning

confidence: 90%

Characterization of Bile Salt/Cyclodextrin Interactions Using Isothermal Titration Calorimetry

et al. 2001

View full text Add to dashboard Cite

show abstract

“…12,13 Guest structure-complex stability relationships provide insights. 5,14,15 By such means we infer, for example, that, in both 4-substituted phenols and their corresponding anions, the primary binding site is the 4-substituent; on the other hand, in 4-substituted benzoic acids, the primary site is the carboxylic acid site, the 4-substituent being a significant but less important site. Upon ionization, the 4-substituent site becomes the dominant site, with binding at the carboxylate site being insignificant.…”

Section: Methodsmentioning

confidence: 97%

Prediction of Binding Constants of α-Cyclodextrin Complexes

Connors¹

1996

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

Proceeding from a phenomenological theory of pairwise interactions (solvent-solvent, solvent-solute, and solute-solute), the binding constant K11 (in M-1) for 1:1 complex formation by alpha-cyclodextrin at a substrate binding site, at 25 degrees C in water, is given by log K11 = -1.74 - [Z] + 0.032(-delta A), where [Z] incorporates solvent-solute (solvation) and solute-solute interactions and delta A is the decrease in nonpolar surface area (in A2 molecule-1) on the substrate that is exposed to solvent when the binding site enters the cyclodextrin cavity. delta A is estimated from the structure of the binding site. Three levels of approximation are described for estimating [Z]. At the third (highest) level, the procedure when applied to 569 complex systems generated predicted values of log K11 that agreed within 0.30 unit of the experimental values in 58% of cases, and that agreed within 1.00 unit in 95% of cases.

show abstract

“…14,15 There are three special cases of present interest. In Case I, K12a ) 0 and K12b ) 0; therefore, eq 3 becomes: and the linear plotting form eq 6 was used:…”

Section: Methodsmentioning

confidence: 99%

“…14 Some of the higher cyclodextrin concentrations were obtained more speedily by sonicating the solutions, followed by equilibration to the experimental temperature of 25°C. Ionic strength was adjusted to 0.10 M with sodium chloride.…”

Section: Methodsmentioning

confidence: 99%

Binding of Cyclodextrins to Alicyclic and Aromatic Substrates: Complex Formation of α-, β-, and γ-Cyclodextrins with Substituted Cyclohexanecarboxylic Acids and Phenylalkanoic Acids

Gadre¹,

Rüdiger

Schneider

et al. 1997

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

0 Complex binding constants of the three native cyclodextrins with seven cyclohexane derivatives (all possessing the carboxylic acid group) and with the series C 6 H 5 (CH 2 ) n COOH (n ) 0 to 4) were measured in aqueous solution at 25°C by potentiometry and the solubility method. These results, combined with literature data, indicate that R-and γ-cyclodextrins bind with comparable strength to both the cyclohexyl and phenyl moieties, with -cyclodextrin binding significantly more strongly. These acid series are compared with several series CH 3 (CH 2 ) n X, where X is CH 3 , COOH, COO -, OH, SO 3 -, etc., and it is concluded that the X group (for X other than methyl) contributes appreciably to complex stability, perhaps by means of an extracavity interaction. The COOH group provides a further augmentation of complex stability. NMR CIS and ROESY results indicate the presence of isomeric complexes in both the cyclohexyl and phenylalkanoic series, and clearly demonstrate the existence of intracavity inclusion. An NOE study of the R-cyclodextrin: cyclohexanecarboxylate system provides evidence for inclusion combined with interaction outside (that is, at the rim of) the cavity.Intense interest in cyclodextrin chemistry in recent years has resulted in the measurement of hundreds of binding constants for complexes comprised of cyclodextrins and aromatic guest molecules. Few systematic investigations into the cyclodextrin binding properties of alicyclic compounds have been made (though some useful results are available 1-12 ). In the present paper we augment these relatively few examples of alicyclic guest systems by examining the binding of the three "native" cyclodextrins (R-, -, and γ-cyclodextrin) with some alicyclic carboxylic acids and, for comparison purposes, some phenylalkanoic acids. These binding studies are supported by nuclear magnetic resonance (NMR) investigations of some of these systems. Experimental SectionMaterialssR-Cyclodextrin, -cyclodextrin, and γ-cyclodextrin (American Maize Products Company) were dried at 95°C for 48 h. Benzoic acid (Aldrich) was recrystallized from water; and phenylalkanoic acids (Aldrich) were recrystallized from water-methanol, their melting points being in good agreement with literature values. 3-Cyclohexenecarboxylic acid (Alfa) and the cyclohexane carboxylic acids (Aldrich) were purified by distillation under reduced pressure. House reverse-osmosis water was further treated with a Sybron/ Barnstead PCS ion-exchange purification system.ApparatussPotentiometric measurements were made with an Orion model 701A pH meter and a Corning semi-micro combination electrode. Spectrophotometric measurements were made with a Hitachi model U-3000 spectrophotometer. The solutions were thermostatted during potentiometric and spectrophotometric measurements at 25°C by means of an external, constant-temperature water bath.NMR experiments were carried out at 500 MHz with a Bruker DRX-500 spectrometer at 303 K with D2O as solvent.ProceduressPotentiometrysThe experimental operation consists of mea...

show abstract

Potentiometric Study of Molecular Complexes of Weak Acids and Bases Applied to Complexes of α-Cyclodextrin with para -Substituted Benzoic Acids

Cited by 77 publications

References 16 publications

Characterization of Bile Salt/Cyclodextrin Interactions Using Isothermal Titration Calorimetry

Characterization of Bile Salt/Cyclodextrin Interactions Using Isothermal Titration Calorimetry

Prediction of Binding Constants of α-Cyclodextrin Complexes

Binding of Cyclodextrins to Alicyclic and Aromatic Substrates: Complex Formation of α-, β-, and γ-Cyclodextrins with Substituted Cyclohexanecarboxylic Acids and Phenylalkanoic Acids

Contact Info

Product

Resources

About