Exploring the Origins of Enthalpy–Entropy Compensation by Calorimetric Studies of Cyclodextrin Complexes

Abstract

Cyclodextrin complexes were used as simple model systems to explore the enthalpy-entropy compensation phenomenon which is often observed in biomolecular processes, e.g. in proteinligand binding. The complexation thermodynamics for the binding of a series of adamantane derivatives to several cyclodextrin hosts were determined by isothermal titration calorimetry in the temperature range 10-55 °C. As for other cyclodextrin complexes, the thermodynamic parameters depended systematically on the structural modifications of the cyclodextrins. Hydroxypropyl chains at the rims of the cyclodextrin hosts changed the thermodynamic fingerprint of binding to all guests by inducing significant increases in the complexation enthalpies and entropies. Similarly, the heat capacity changes upon complexation also showed a linear dependence on the number of hydroxypropyl chains. The altered complexation thermodynamics was ascribed to the increased dehydration of polar groups on the guest by the hydroxypropyl chains on the host. This unfavorable interaction destabilized the complexes as the enthalpic penalty was only partially compensated by the gain in entropy. The degree of enthalpyentropy compensation depended on the guest molecule and seems to be related to the hydrophilicity/hydrophobicity of the desolvated molecular surface.

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition

“…5.2 × 10 4 [77]. However, the observed order of magnitude lower K a , compared to native β-CD complexes, is not uncommon for inclusion complexes formed with HP-β-CD, where the observed association constants drop as the hydroxylpropylation degree increases [83]. This drop has been attributed to their extended hydrophobic cavity, which imposes an enthalpic penalty due to dehydration of the polar groups on the guest.…”

“…The complexation of the pendant adamantane groups with HP-β-CD was therefore driven by contributions of both enthalpy and entropy, whereas complexation with native β-CD was mainly enthalpy driven [84]. It has been described that, in the case of neutral polar groups, in this case a secondary amide, the net gain in the entropic factor is unable to compensate for the increased enthalpy, leading to a tenfold decrease in the association constant [83]. These results further support the observations made from the turbidimetry measurements and highlight the importance of linker and host compatibility in the synthesis of thermoresponsive supramolecular assemblies.…”

Understanding the Interaction of Polyelectrolyte Architectures with Proteins and Biosystems

“…Jen‐Jacobson and co‐workers showed that EEC exists in systems of biological relevance [13, 14, 49, 136] . Synthetic systems have been studied with equal intensity, [134] and from the vast amount of literature we only cite the very recent investigation by Schönbeck and Holm [137] on the EEC for complexes of cyclodextrin with various host molecules. Dragan et al.…”

Wechselwirkung von Polyelektrolyt‐Architekturen mit Proteinen und Biosystemen

“…Jen‐Jacobson und Mitarbeiter zeigten, dass die EEC auch in Systemen von biologischer Relevanz vorkommt [13, 14, 49, 136] . Synthetische Systeme wurden mit gleicher Intensität untersucht, [134] daher zitieren wir aus der umfangreichen Literatur nur die sehr aktuelle Untersuchung zur EEC für Komplexe von Cyclodextrin mit verschiedenen Wirtmolekülen durch Schönbeck und Holm [137] . Kürzlich haben Dragan et al.…”

“…[13,14,49,136] Synthetische Systeme wurden mit gleicher Intensitätu ntersucht, [134] daher zitieren wir aus der umfangreichen Literatur nur die sehr aktuelle Untersuchung zur EEC fürK omplexe von Cyclodextrin mit verschiedenen Wirtmolekülen durch Schçnbeck und Holm. [137] Kürzlich haben Dragan et al vorgeschlagen, dass die EEC mit der Freisetzung oder Aufnahme von Wasser zusammenhängen kçnnte. [11] In Abschnitt 3d iskutieren wir unsere aktuellen Untersuchungen zur EEC fürd ie Wechselwirkung von dPGS mit verschiedenen Proteinen, die zu den gleichen Schlussfolgerungen kommen.…”