Protonation of a Spherical Macrotricyclic Tetramine: Water Inclusion, Allosteric Effect, and Cooperativity

The spherical macrotricyclic cryptand tetramine "C24" (1) displays remarkable protonation behaviour. It undergoes protonation in four successive steps for which pK_a values of 11.17±0.05, 10.28±0.04, 6.00±0.06 and 3.08±0.08 have been determined at 298 K. The unusually close values for the first two protonations provide evidence for the encapsulation of a water molecule serving as effector for the second protonation, which is consistent with earlier observations that the exchange of protons bound in the diprotonated species with solvent protons is unusually slow and that ¹⁷ O NMR spectra show the presence of an oxygen centre in the same species quite distinct from that of solvent water. Encapsulation of water is also observed in the solid state in the picrate salt of the triprotonated form of 1 and has been characterised by means of X-ray structural determination.