High binding constants of 19 inorganic cations with the cucurbit[n]uril homologues (CBn, n = 5, 6, 7, 8) in water were determined and the far-reaching consequences and interferences of the high affinities (millimolar to micromolar) are discussed.

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts.

The release of two organic guests from cucurbit[7]uril (CB7) was selectively monitored by the stopped‐flow method in aqueous solutions of inorganic salts to reveal the mechanistic picture in detail. Two contrasting mechanisms were identified: The symmetric dicationic 2,7‐dimethyldiazapyrenium shows a cation‐independent complex dissociation mechanism coupled to deceleration of the ingression in the presence of alkali and alkaline earth cations (Mⁿ⁺) due to competitive formation of CB7–Mⁿ⁺ complexes. A much richer, unprecedented kinetic behaviour was observed for the ingression and egression of the monocationic and non‐symmetric berberine (B⁺). The formation of ternary complex B⁺–CB7–Mⁿ⁺ was unambiguously revealed. A difference of more than two orders of magnitude was found in the equilibrium constants of Mⁿ⁺ binding to B⁺–CB7 inclusion complex. Large cations, such as K⁺ and Ba²⁺, also promoted B⁺ expulsion from the ternary complex in a bimolecular process. This study reveals a previously hidden mechanistic picture and motivates systematic kinetic investigations of other host–guest systems.

The dynamics and activation parameters of alkaloid entry into and exit from cucurbit[7]uril significantly depend on the substitution pattern.

The effect of headgroup variation on the association of supramolecular amphiphiles composed of 4-sulfonatocalix[6]arene (SCX6) and cationic surfactant possessing tetradecyl substituent was studied in aqueous solutions at pH 7. When the surfactant contained hydrophilic trimethylammonium, pyridinium, or 1-methylimidazolium headgroup, highly reversible temperature-responsive nanoparticle–supramolecular micelle transformation could be attained at appropriately chosen component mixing ratios and NaCl concentrations. In these cases, the substantial negative molar heat capacity change (ΔC_p) rendered nanoparticle formation strongly endothermic at low temperature, whereas the assembly to supramolecular micelle was always accompanied by enthalpy gain. The ΔC_p values became less negative when the charge density and the hydrophilic character of the surfactant headgroup diminished. The association of the more hydrophobic 6-methoxyquinolinium and quinolinium surfactants with SCX6 did not lead to supramolecular micelle formation because the self-assembly into nanoparticles was highly exothermic.

The inclusion of protonated (−)-tetrahydropalmatine (THP⁺) and dehydrocorydaline (DHC⁺), natural alkaloids, in the cavity of cucurbit[7]uril was monitored in real time by a spectrofluorimetric method in water at various temperatures. Both guests produced 1 : 1 complexes in enthalpy controlled processes without any detectable intermediates. The tight entrance of CB7 imposed substantial steric hindrance for encapsulation making the entry into the host several orders of magnitude slower than diffusion. Despite the ∼6 kJ mol⁻¹ lower activation enthalpy, the rate constant of THP⁺ ingression into CB7 was about 44-fold smaller at 298 K than that of DHC⁺ as a consequence of the considerably negative activation entropy of the former binding. The egression rates of the two studied alkaloids differed to a much lesser extent because the lower energy barrier of THP⁺ release was almost compensated by the unfavourable activation entropy. In comparison with the kinetics of the reversible confinement of the palmatine parent compound, the presence of the methyl substituent on the aromatic heterocyclic ring in DHC⁺ barely modified the rate constant of entry into CB7 but caused about 10-fold increase in the dissociation rate at 298 K.