Search

Amongst macrocyclic receptors, cucurbit[7]uril (CB7) and β-cyclodextrin (β-CD) stand out as good receptors for hydrophobic species in aqueous solutions. In contrast to the frequently investigated hosting of aliphatic compounds, the inclusion of aromatic guests within these hosts is far less explored. Taking this into account, we have studied the complexation of various benzene derivatives with CB7 and β-CD in water by means of isothermal titration microcalorimetry and in a wide temperature range (5−65 °C). ROESY and 1H NMR experiments were carried out to investigate the inclusion of 4-tert-butylphenol into the host cavities. The inclusion of guests within the CB7 cavity in vacuo was also studied by performing DFT calculation using the bp86/tzvp level of theory. The examined host-guest systems exhibited distinct ΔrH° and ΔrS° temperature dependence, resulting in weak variation of standard Gibbs energy with temperature. The complexation thermodynamics at lower temperatures was in agreement with the classical interpretation of the hydrophobic effect, whereas the binding at higher temperatures was in line with the non-classical rationale.

Cyclodextrins and cucurbiturils are very good receptors of hydrophobic species in water. The product stability (logK > 10 for complexes involving neutral guests and cucurbiturils were reported) is a consequence of strongly exothermic association, rationalized by non-classical hydrophobic effect (release of energetically rich cavity water). However, our recent study of the adamantyl-based guest inclusion within β-cyclodextrin (β-CD) revealed an almost complete compensation of ΔrH°(T) and –TΔrS°(T) contributions to logK temperature dependence. The results could be explained by the Frank-Evans model of adamantane hydration at lower (classical hydrophobic effect) and gradual “iceberg melting” at higher temperatures. We have therefore decided to study the complexation of both (poly)cyclic and linear aliphatic compounds with cucurbit[7]uril (CB7) and β-CD in a wide temperature range, both experimentally (ITC, ROESY NMR spectroscopy) and computationally (classical, solvent-explicit MD simulations). The investigated guests were chosen with the aim of supressing all thermodynamic contributions to hosting apart those associated with the hydrophobic effect. The study provided missing pieces to a jigsaw puzzle explaining the thermodynamic contributions to standard complexation Gibbs energies, as well as insights into hydration of guest and host cavities. Apart from that, intriguing differences concerning the enthalpic and entropic effect of CB7 and β-CD cavity dehydration were revealed.

Diamantane derivatives combined with cucurbit[n]urils have received significant attention in the field of supramolecular chemistry due to their outstandingly high complex stability constants, reaching above petamolar values for positively charged diamantane diammonium salts and cucurbit[7]uril in water. On the other hand, their complexation with cyclodextrins has been rarely investigated.2 We have therefore studied temperature and solvent effects on the complexation of diamantane alcohols with cucurbit[7]uril and β-cyclodextrin in water and structured organic solvents (formamide, ethylene glycol) by means of isothermal titration calorimetry and NMR spectroscopy. The complexes of apical derivatives with CB7 in water were the most stable products (log K > 7), whereas the complexation of 4-DiaOH with β-CD was the most favorable in formamide. For most of the studied host-guest systems a significant temperature dependence of ΔrH° and ΔrS° was observed, which resulted in an almost complete enthalpy-entropy compensation. For these systems complexation thermodynamics was in line with the classical rationale of the solvophobic effect at lower temperatures, and the non-classical explanation at higher ones. The results of 1H NMR titrations were in accord with the thermodynamic studies and have revealed an interesting difference in complex formation kinetics between cucurbit[7]uril and β-cyclodextrin hosts.

Regioisomeric mannoconjugates of naphthyl alcohols were synthesized by coupling of protected mannopyranose and corresponding esters of bromoacetic acid with 1- and 2-naphthyl moieties. Their complexation and the complexation of corresponding nonfunctionalized alcohols with cyclodextrins (α-, β- and γ-) and cucurbit[7]uril was explored by means of isothermal titration calorimetry, spectrophotometry, fluorimetry and NMR spectroscopy. The complexation of 2-naphthol with cucurbit[7]uril was thermodynamically most favorable. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy-entropy compensation was observed for some of the examined host-guest systems. In these cases, the complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non- classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in agreement with the results obtained by other experimental methods and have revealed an interesting difference in complex formation kinetics among the investigated host molecules.

Regioisomeric mannoconjugates of naphthyl alcohols were synthesized by coupling of protected mannopyranose and corresponding esters of bromoacetic acid with 1- and 2- naphthyl moieties. Their complexation and the complexation of corresponding nonfunctionalized alcohols with cyclodextrins (α-, β- and γ-) and cucurbit[7]uril was explored by means of isothermal titration calorimetry, spectrophotometry, fluorimetry and NMR spectroscopy. The complexation of 2- naphthol with cucurbit[7]uril was thermodynamically most favorable. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy- entropy compensation was observed for some of the examined host-guest systems. In these cases, the complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in agreement with the results obtained by other experimental methods and have revealed an interesting difference in complex formation kinetics among the investigated host molecules.

The temperature and solvent effect on the complexation of various guests (Figure 1) with α-, β- and γ-cyclodextrin and cucurbit[7]uril was explored experimentally and by means of molecular dynamics simulations. The stability constants of all investigated complexes were by far the highest with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in almost complete enthalpy-entropy compensation was observed for most explored host-guest systems. For those systems complexation thermodynamics was in line with the classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. The optimized inclusion complex structures corresponded to those deduced by means of NMR spectroscopy and the experimentally obtained and calculated ΔrG° were in very good agreement.

Diamantane derivatives are excellent guests for cucurbiturils in aqueous solutions, forming complexes with stability constants reaching above petamolar values. On the other hand, their complexation with cyclodextrins has been scarcely explored. We therefore studied temperature and solvent effects on the complexation of diamantane alcohols with cucurbit[7]uril, β- and γ- cyclodextrin by means of isothermal titration calorimetry and NMR spectroscopy. The stability constant among all investigated complexes was by far the highest in the case of the diol derivate with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in an almost complete enthalpy- entropy compensation, was observed for most studied host-guest systems. The corresponding complexation thermodynamics were in line with the classical rationale of the solvophobic effect at lower temperatures, and the non- classical explanation at higher ones. The results of 1H NMR titrations and ROESY experiments were in line with the thermodynamic studies and have revealed an interesting difference in complex formation kinetics between cucurbit[7]uril and β-cyclodextrin.

The temperature and solvent effect on the complexation of various guests with α-, β- and γ-cyclodextrin and cucurbit[7]uril was explored experimentally and by means of molecular dynamics simulations. The stability constants of all investigated complexes were by far the highest with cucurbit[7]uril in water. A pronounced temperature dependence of ΔrH° and ΔrS°, resulting in almost complete enthalpy- entropy compensation was observed solely in water. The complexation thermodynamics was in line with classical rationale of the hydrophobic effect at lower temperatures, and the non-classical explanation at higher ones. Unlike in water, the hosting in formamide and ethylene glycol could be attributed to non- classical solvophobic effect. The optimized inclusion complex structures corresponded to those deduced by means of NMR spectroscopy and the experimentally obtained and calculated ΔrG° were in very good agreement. The carried out research bridged the gap between the classical and non-classical rationale of hydrophobic effect and demonstrated that solvophobically driven formation of inclusion complexes is not a water-limited phenomenon. However, among explored structured solvents, water stood out as unique solvation and complexation medium.