The partial dethreading of stable host/guest, 2:1 [3]pseudorotaxanes of alpha -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 taken 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 heating 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 alpha -cyclodextrin rings and conversion to a [2]pseudorotaxane. Analysis of available thermodynamic data reveals that following this partial decomplexation, 3-4 methyl groups are exposed to the aqueous solvent. The dissociation 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 cyclodextrin complexes. These slow rates have been attributed primarily to the breaking 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 groups of the guest molecules. The observed partial dethreading process is not reversible; it is reproducible after recrystallization of the 2:1 complex. This thermodynamic behavior was not observed for an analogous alpha -cyclodextrin/11-aminoundecanoic acid complex in aqueous solution because crystallization of the 2:1 complexes could not be achieved.