Zwitterionic Amino-Acid-Derived Polyacrylamides with a Betaine Twist - Synthesis and Characterization

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Organic Synthesis

Background:

• Amino-acid-derived polyzwitterions and polybetaines (PBs) are explored as alternatives to non-ionic polymers for applications like enhanced tumor permeability.
• A strategy was developed to synthesize novel polymers by quaternizing the amine in side-chain functional groups, aiming to merge the benefits of PBs and polyzwitterions.

Purpose of the Study:

• To synthesize amino-acid-derived polyzwitterions and develop a method to quaternize their amine groups.
• To investigate the impact of a permanent positive charge on the physiochemical properties of these novel polymers.
• To compare the properties of methylated and non-methylated zwitterionic polymers.

Main Methods:

• Reversible addition-fragmentation chain-transfer (RAFT) polymerization was employed for monomer polymerization, including kinetic studies.
• Post-polymerization modification (PPM) of Poly(N-acryloxysuccinimide) was used to create methylated and non-methylated polymers for comparative analysis.
• Circular dichroism, pH titration, and ζ-potential measurements were utilized to characterize the polymers' structural integrity and charge behavior.

Main Results:

• Circular dichroism confirmed that the stereocenter remained intact during post-polymerization modification.
• pH titration and ζ-potential measurements indicated that the methylated polymer exhibited a negative ζ-potential across the measured pH range, maintaining zwitterionic character over a broader range than its non-methylated counterpart.
• Both synthesized polymers demonstrated good biocompatibility, being well-tolerated by mammalian cells at concentrations up to 1 mg mL⁻¹.

Conclusions:

• A new class of polymers combining advantages of polybetaines and amino-acid-derived polyzwitterions was successfully introduced.
• The study highlights the significant influence of a permanent charge on the physiochemical properties of zwitterionic polymers.
• These novel polymers show promise for biomedical applications due to their tunable properties and biocompatibility.