Complexation forces in aqueous solution. Calorimetric studies of the association of 2-hydroxypropyl-b-cyclodextrin with monocarboxylic acids or cycloalkanols.

The formation of complexes between 2-hydroxypropyl-b-cyclodextrin and monocarboxylic acids or cycloalkanols has been studied calorimetrically at 298 K in phosphate buffer, pH 11.3. The forces involved in the assocn. process are discussed in the light of the signs and values of the thermodn. parameters obtained: assocn. enthalpy, binding const., Gibbs free energy, and entropy. For monocarboxylic acids, hydrophobic interactions are the primary force detg. complexation, as indicated by the small enthalpies and by the high and pos. entropies. For the cycloalkanols, instead, enthalpies are neg. and entropies pos. or neg., depending on the solvent medium employed, namely water or phosphate buffer. The most important requirement for the formation of the complex is a good spatial fit between the two interacting mols. A cavity elongation effect occurs because of the presence of the hydroxypropyl groups on the rim of the macrocycle. The relative contribution of hydrophobic and van der Waals interactions varies with the dimensions of the guest mols. A linear correlation exists between enthalpy and entropy of complexation, underlying that inclusion is a process dominated by hydration phenomena and ascribed to the modifications experienced by the solvent in the hydration shells of the interacting substances

Thermodynamics of inclusion complexes of natural and modified cyclodextrins with propranolol in aqueous solution at 298 K

The assocn. const., std. Gibbs energy, enthalpy and entropy for formation of inclusion complexes of propranolol, a b-blocker, with various natural and modified cyclodextrins have been detd. by calorimetry at 298 K. Both natural and methyl-modified a-cyclodextrins do not form complexes, while b- and g-cyclodextrins do. Complexing ability of 2-hydroxypropyl-b-cyclodextrin depends on the av. substitution degree. For g-cyclodextrin, hydrophobic interactions play the major role in binding the guest. The assocn. of natural and modified b-cyclodextrins is ruled by van der Waals interactions and hydrogen bonding because of the tighter fit of the guest into the cavity. Decreasing pH dets. increasingly neg. values of the assocn. enthalpies

Solvent effects on the complexation of 1-alkanols by parent and modiefied cyclodextrins. Caloimetric studies at 298K

The formation of complexes of parent and alkylated cyclodextrins (CDs) with 1-heptanol and 1-octanol has been studied calorimetrically at 298 K in water and in concentrated aqueous solutions of urea. The forces involved in the association process are discussed in the light of the signs and values of the thermodynamic parameters obtained: association enthalpy, binding constant, Gibbs free energy, and entropy. It was inferred that: (i) in water, the formation of complexes for parent and substituted a-cyclodextrins (aCDs) is determined by enthalpy. For parent and substituted b-cyclodextrins (bCDs), instead, hydrophobic interactions are the prevailing forces determining complexation, as indicated by the small and negative or positive enthalpies and by the high and positive entropies. (ii) In urea, hydrophilic interactions are attenuated. The formation of complexes with alkylated CDs does not occur. (iii) The analysis of the thermodynamic properties confirms that inclusion is a process dominated by hydration phenomena. Modifications experienced by the solvent water in the hydration shells of the interacting substances upon association determine the formation of the complexes

Water-mediated interactions between benzene rings. Calorimetric studies of aromatic model compounds in aqueous solutions at 298 K

Pairwise enthalpic interaction coeffs. of the virial expansion of the excess enthalpies were detd. at 298 K by measuring the enthalpies of diln. in aq. soln. of binary aq. solns. contg. 4-hydroxyphenylacetic acid, 2-phenylethanol, 3-phenylpropanol, 3-phenylpropionic acid, L-tyrosine, and L-phenylalanine. Coeffs. obtained are compared with those already reported in the literature for other arom. substances in aq. solns. Not withstanding the similarity of the substances employed, the values of the enthalpic coeffs. range from highly neg. to highly pos., an indication that the interactions between the benzene rings are largely dependent on the nature of the functional groups. For hydroxylated substances, enhanced hydrophobic interactions are operating, probably for the simultaneous interaction between the benzene rings and the alkyl chains, forced by the hydroxyl group. On the contrary, the strength of hydrophobic interactions in the solns. of the amino acids depend on the pH of the medium and on the presence of hydroxyl group on the arom. ring. The data are discussed according to an interaction model which assumes the presence of a preferential configuration between two hydrated mols

The cavity elongation effect. Calorimetric studies of the complexes of long-chain carboxylic acids with methyl-a-cyclodextrin in aqueous solutions

The formation of complexes between methyl-a-cyclodextrin (MaCD) and monocarboxylic acids from C5 to C12 or cycloalkanols has been studied calorimetrically at 298 K in aq. phosphate buffer, pH 11.3. The forces involved in the assocn. process are discussed according to the signs and values of the thermodn. parameters obtained: assocn. enthalpy, assocn. const., Gibbs energy, and entropy. Methyl-a-cyclodextrin forms 1:1 inclusion complexes with monocarboxylic acids, characterized by a monotonic increase in the values of enthalpies and assocn. consts. at increasing alkyl chain length. Assocn. is characterized by neg. enthalpies and by pos. entropies, which dets. large assocn. consts. That behavior is compared to the unusual trend in the values of the assocn. consts. shown by the parent a-cyclodextrin interacting with the same monocarboxylic acids. The model proposed to rationalize the present data provides a cavity elongation effect. Namely, because of the presence of the Me groups on the outside, the cavity behaves as it were deeper than that of the parent cyclodextrin. The assocn. with cycloalkanols (cyclohexanol, cycloheptanol, cyclooctanol and 1-cyclohexyl-ethanol) is characterized by lower entropies, as detd. by the enhanced neg. contribution originating from the tighter fit of the guest into the cavity

A calorimetric study of the interactions in the aqueous solutions of lysozyme in the presence of denaturing cosolvents

A thermodynamic method is reported to monitor the chemical denaturation of lysozyme. Heats of dilution of the protein in concentrated aqueous solutions of urea or ethanol have been determined at 298.15 K by flow microcalorimetry. The pairwise enthalpic interaction coefficients of the protein in the different solvent media are derived. These parameters allow to gain information about the influence of the cosolvents on the interactions acting between two interacting hydrated molecules of lysozyme, hence on the denaturation process. At increasing urea concentration, up to about 6 mol kg−1, the values of the interaction coefficients are large and negative and remain almost unaltered. The invariance of the coefficients underlines that, even in highly concentrated urea, the hydration shell of the protein is such to maintain essentially unaltered the native conformation. At higher urea concentrations, a sudden change in the sign of the coefficients monitors the variation in the interactions between two hydrated denatured protein molecules. The same trend is found when ethanol is the cosolvent. At increasing concentration of the cosolvent, coefficients are, at first, almost invariant. After that, denaturation occurs, detected as a jump toward much more negative values. The results obtained are rationalized on the basis of those previously found for small model molecules in concentrated solutions of urea or ethanol. The thermodynamic framework allows useful comments to be made on the possible mode of action of the two cosolvents on the stability of proteins in solution

Complexation of natural and methylated b-cyclodextrin with long-chain carboxylic acids in aqueous solutions. Calorimetric studies at 25°C

The formation of complexes between b-cyclodextrin or methyl-b-cyclodextrin and monocarboxylic acids from C5 to C12 has been studied calorimetrically at 298 K in aq. buffer phosphate, pH 11.3. When a complex forms, calorimetry enables the calcn. of both the enthalpy and the assocn. const., from which the Gibbs free energy and the entropy of the process can be obtained. The forces involved in the assocn. process are then discussed in the light of the signs and values of the thermodn. parameters obtained. For b-cyclodextrin, 1:1 inclusion complexes form, characterized by an irregular variation in the values of enthalpies, entropies and assocn. consts. at increasing alkyl chain length. A model is proposed to explain this unusual behavior for acids longer than ten carbon atoms. The assocn. involving methyl-b-cyclodextrin shows, instead, a regular variation of the thermodn. parameters up to the C12 term. An elongation of the cavity effect is discussed: the cavity behaves as it were deeper than that of the natural cyclodextrins. Assocn. is characterized prevailingly by hydrophobic interactions; for the longer terms, the high and almost invariant entropic contribution dets. the large assocn. consts., notwithstanding the pos., unfavorable enthalpic contribution. This is an indication that the relaxation of water mols. from the hydrophobic hydration shells of the external Me groups is the contribution that mainly dets. the assocn. process

Thermodynamics of inclusion complexes of natural and modified cyclodextrins with acetylsalicylic acid and ibuprofen in aqueous solution at 298K

Thermodynamic parameters for the association of natural and substituted -, -, and -cyclodextrins with acetylsalicylic acid, salicylic acid and ibuprofen have been determined by isothermal titration calorimetry. Analysis of the data shows that complexes form, all having 1:1 stoichiometry. The shapematching between the host and guest is the factor determining the values of the thermodynamic quantities. In the case of the smallest cyclodextrin interacting with acetylsalicylic acid and salicylic acid, the parameters indicate that hydrophobic interactions play the major role. Association occurs through the shallow inclusion of the benzene ring into the cavity. In the case of substituted -cyclodextrins, instead, inclusion of the benzene ring is deeper and the tight fitting of the guest molecule to the cavity makes the enthalpy and entropy to be both negative. Ibuprofen interacts through its isobutyl group: the values of the association constants are very high for -cyclodextrins as determined by the large and positive entropies due to the relaxation of water molecules from the cavity and the hydration spheres of the interacting substances. For all systems, a compensatory enthalpy–entropy relationship exists unless for those involving -cyclodextrins and ibuprofen