Chiro-optical and solution properties of stimuli responsive amino acid-deriving polymers

The design of chiral synthetic polymers capable of self-assembling into stable secondary structures represents an attracting approach with important biological implications, from selective subcellular localization to protein surface mimicry and recognition. In previous work, the first examples of a new class of stimuli-responsive bioinspired chiral polymers, namely polyamidoaminoacids (PAACs), were obtained by the polyaddition of L-, D- and D,L-arginine with N,N′-methylenebisacrylamide (ARGO7). L-ARGO7 proved highly citobiocompatible and preferentially localized in the perinuclear region of Balb/3T3 cells. Circular dichroism (CD) and molecular dynamic modeling studies showed that L- and D-ARGO7 folded into rigid conformations reminiscent of the protein hairpin motif, which underwent rapid and reversible interconversions with pH.[2] In order to demonstrate that the observed behavior was a general one, a library of amphoteric PAACs were synthesized from different L-, D- and D,L-aminoacids. They were obtained in 92% yield by stepwise polyaddition with N,N'-methylenebisacrylamide in water at pH > 10 and 50 °C for 6 days. Acid−base and chiro-optical properties were evaluated to gain insights into their pH-dependent conformational behavior in water and establishing structure-properties correlations. The thermodynamic results for the deprotonation of the amine- and carboxyl groups never displayed a typical "polyelectrolyte" behavior. In water, the "a" values of PAACs in the Mark-Houwink-Sakurada equation ranged between 0.6 and 0.8, suggesting that they assumed coiled structures. Circular dichroism spectra, recorded for all PAACs in the 3-12 pH interval, were consistent with the presence of pH-dependent ordered secondary structures. Future studies on cell internalization will assess the potential of PAACs for establishing chirality-dependent selective interactions with cell components.