The protonation thermodynamics of cyclodextrin-containing polymers for drug inclusion

A poly(amido-amine), PAA, bearing beta-CD units in the side chain was synthesized by a polyaddition reaction of 1,4-bis-acryloyl-piperazine with 6-monodeoxy-6-monoamino-beta-cyclodextrin (beta-CD-NH2). Unlike the simple beta-CD-NH2 with a greater basicity constant (log K = 8.60), the polymer revealed an unusual polyelectrolyte behaviour with a lower basicity constant (log KA degrees A = 6.29) of the tertiary nitrogen atom, that is strongly dependent on the degree of protonation alpha of the whole macromolecule. It follows the modified Henderson-Hasselbalch equation with n = 1.75, in a wide alpha-range. The greater (-46.1 kJ/mol) and the lower (-27.6 kJ/mol) enthalpy (Delta HA degrees) changes of the compounds were in line with the protonation of a primary or a tertiary nitrogen atom. The calorimetric data suggested that the PAA protonation destroyed a packing structure formed by two rigid beta-CD side chains interacting head-to-head. The UV spectrophotometric data showed that the PAA exhibits affinity towards the l-ascorbic acid at low pH (pH 2.46) with an isosbestic point at 241 nm and a slight blue shift of the maximum absorption of the ascorbic acid (244 nm) on PAA additions.