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 H-1 and C-13 NMR spectroscopy, and their average molecular weight determined by size exclusion chromatography. The polymerization rates were investigated by means of H-1 NMR spectroscopy. In both cases, the experimental data were consistent with pseudo-second-order kinetics. The calculated kinetic constants were k(c,BP) = 8.10 x 10(-3) min(-1) L mol(-1) and k(c,BAC) = 1.41 x 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.