Versatile Synthesis of Amino Acid Functional Polymers without Protection Group Chemistry

Abstract

The copolymerization of N-isopropylacrylamide (NiPAm) with aldehyde functional monomers facilitates postpolymerization functionalization with amino acids via reductive amination, negating the need for protecting groups. In reductive amination, the imine formed from the condensation reaction between an amine and an aldehyde is reduced to an amine. In this work, we categorize amino acids into four classes based on the functionality of their side chains (acidic, polar neutral, neutral, and basic) and use their amine groups in condensation reactions with aldehyde functional polymers. The dynamic nature of the imine as well as the versatility of reductive amination to functionalize a polymer with a range of amino acids is highlighted. In this manner, amino acid functional polymers are synthesized without the use of protecting groups with high yields, demonstrating the high functional group tolerance of carbonyl condensation chemistry and the subsequent reduction of the imine. Prior to the reduction of the imine bond, transimination reactions are used to demonstrate dynamic polymers that shuffle from a glycine- to a histidine-functional polymer.

Poly(acryloyl hydrazide), a versatile scaffold for the preparation of functional polymers: synthesis and post-polymerisation modification

“… 27 Despite all of these features, the use of poly(hydrazide)s as a reactive scaffold had been limited to the preparation of glycopolymers, 29 , 31 and for pH-responsive drug delivery. 32 – 36 Alternative elegant strategies using poly(alkoxyamine)s 37 , 38 and poly(aldehyde)s 39 – 41 have also been explored.…”

Using Synergistic Multiple Dynamic Bonds to Construct Polymers with Engineered Properties

“…We have reported the development of dynamic covalent polymers combined with hydrophobic forces to produce a range of switchable amino acid copolymers. PNIPAM copolymers where polymerized with an aldehyde functional comonomer and amino acid were conjugated onto the polymers forming dynamic copolymers with tunable temperature responsive properties and dynamic and bioinspired functionalities . We furthered this approach (development of carbonyl functional polymers) to produce doubly dynamic 3D‐printable macroporous cryogels, this time combining oxime chemistry and hydrogen bonding ( Figure ) .…”

A Guideline for the Synthesis of Amino‐Acid‐Functionalized Monomers and Their Polymerizations

“…Recently, Brisson et al reported the conjugation of amino acids to polymers with aldehyde groups in the side chain (Figure 26). [139,140] In a first step, a Schiff base was formed between the amine group and the aldehyde using acetic acid as the reaction solvent. Then, this reversible covalent bond was reduced with the aid of sodium borohydride, yielding irreversible bound histidine moieties in the polymer side chain.…”