Water Encapsulation in a Polyoxapolyaza Macrobicyclic Compound

A new heteroditopic macrobicyclic compound (t2pN5O3) containing two separate polyoxa and
polyaza
compartments was synthesized in good yield through a [1 + 1] “tripod–tripod
coupling” strategy. The X-ray crystal structure of H3t2pN5O33+ revealed the
presence of one encapsulated water molecule accepting two hydrogen
bonds from two protonated secondary amines and donating a hydrogen
bond to one amino group. The acid–base behavior of the compound
was studied by potentiometry at 298.2 K in aqueous solution and at
ionic strength 0.10 M in KCl. The results revealed unusual protonation
behavior, namely a surprisingly low fourth protonation constant contrary
to what was expected for the compound. 1H NMR and DOSY
experiments, as well as molecular modeling studies, showed that the
water encapsulation and the conformation observed in the solid state
are retained in solution. The strong binding of the encapsulated water
molecule, reinforced by the cooperative occurrence of a trifurcated
hydrogen bond at the polyether compartment of the macrobicycle, account
for the very low log K4H value
obtained.