Novel Amphoteric Cystine-Based Poly(amidoamine)s Responsive to Redox Stimuli

Novel poly(amidoamine)s (PAAs) containing disulfide linkages regularly arranged along the polymer chain, namely BP-CY and BAC-CY, were synthesized by stepwise polyaddition of L-cystine to 1,4-bis(acryloyl)piperazine (BP) and 2,2-bis(acrylamido)acetic acid (BAC), respectively. Even if L-cystine contains four acid hydrogens, no evidence of cross-linking was found. All products were characterized by 1H and 13C NMR spectroscopy, and their average molecular weight determined by size exclusion chromatography. The polymerization rates were investigated by means of 1H NMR spectroscopy. In both cases, the experimental data were consistent with pseudo-second-order kinetics. The calculated kinetic constants were kc,BP = 8.10 × 10-3 min-1 L mol-1 and kc,BAC = 1.41 × 10-3 min-1 L mol-1 for the polyaddition of L-cystine to BP and BAC, respectively. A potentiometric study was carried out of BP-CY and BAC-CY speciation as a function of pH, and the electrochemical activity of their disulfide bonds as a function of pH was investigated by cyclic voltammetry on hanging drop mercury electrode, revealing many analogies with parent L-cystine. BP-CY and BAC-CY degraded in aqueous systems at a rate similar to that usually reported for PAAs. In the presence of reducing agents, however, they degraded completely in a few minutes. Preliminary biocompatibility in vitro tests showed that both BP-CY and BAC-CY are devoid of appreciable toxicity.