Partial thermal dethreading of [3]pseudorotaxanes of alpha-cyclodextrin with linear aliphatic alpha,omega-amino acids in aqueous solution

The partial dethreading of stable host/guest, 2:1 [3]pseudorotaxanes of alp ha -cyclodextrin with 12-aminododecnnoic acid in aqueous solutions has been studied by high-precision differential scanning calorimetry (DSC) and NMR spectroscopy. For samples in which crystallization of the 2:1 complex had t aken place at 10 degreesC, DSC heating scans revealed a heat capacity (C,) anomaly at temperatures higher than the dissolution temperature (similar to 60 degreesC). This endothermic C,peak is strongly dependent upon the heati ng rates used and is characterized by a net enthalpy change DeltaH = 17.15 +/- 1.67 kJ/mol. The peak is attributed to the dethreading of one of the al pha -cyclodextrin rings and conversion to a [2]pseudorotaxane. Analysis of available thermodynamic data reveals that following this partial decomplexa tion, 3-4 methyl groups are exposed to the aqueous solvent. The dissociatio n kinetics have been analyzed via a one-step Arrhenius model leading to an activation energy E, = 140.1 +/- 8.1 kJ/mol and a frequency factor A = 1.7 +/- 0.1 x 10(17) s(-1). The reaction rates are very slow, 3.8 +/-0.6 x 10(- 5) s(-1) at 65 degreesC, compared to dissociation rates of other cyclodextr in complexes. These slow rates have been attributed primarily to the breaki ng of the hydrogen bonds between the two cyclodextrin rings in the dimer of the [3]pseudorotaxane and also to the high hydrophilicity of the end group s of the guest molecules. The observed partial dethreading process is not r eversible; it is reproducible after recrystallization of the 2:1 complex. T his thermodynamic behavior was not observed for an analogous alpha -cyclode xtrin/11-aminoundecanoic acid complex in aqueous solution because crystalli zation of the 2:1 complexes could not be achieved.