A functional monomer carrying a carboxylate and a protected primary ammonium group is synthesized from itaconic acid. When copolymerized with dimethyl acrylamide and 4-methacryloyloxybenzophenone, cross-linkable polyzwitterions are obtained. These are converted to surface-attached polyzwitterion networks by simultaneous UV-triggered C,H insertion reactions. The resulting polyzwitterion-coated substrates were studied by surface plasmon resonance spectroscopy measurements, ζ potential and various biological assays. They were (expectedly) protein repellent, yet at the same time (and unexpectedly) cell-adhesive and antimicrobially active. This was attributed to stimulus-responsiveness of the polyzwitterion (confirmed by the ζ potential measurements), which enables charge adjustment at different pH values. When protonated, the polyzwitterions become amphiphilic polycations and, in this state, kill bacteria upon contact like their parent structures (polymer-based synthetic mimics of antimicrobial peptides, SMAMPs).

A series of asymmetrically disubstituted diitaconate monomers is presented. Starting from itaconic anhydride, functional groups could be placed selectively at the two nonequivalent carbonyl groups. By using 2D NMR spectroscopy, it was shown that the first functionalization step occurred at the carbonyl group in the β position to the double bond. These monomers were copolymerized with N,N-dimethylacrylamide (DMAA) to yield polymer-based synthetic mimics of antimicrobial peptides (SMAMPs). They were obtained by free radical polymerization, a metal-free process, and still maintained facial amphiphilicity at the repeat unit level. This eliminates the need for laborious metal removal and is advantageous from a regulatory and product safety perspective. The poly(diitaconate-co-DMAA) copolymers obtained were statistical to alternating, and the monomer feed ratio roughly matched that of the repeat unit content of the copolymers. Investigations of varied R group hydrophobicity, repeat unit ratio, and molecular mass on antimicrobial activity against Escherichia coli and on compatibility with human keratinocytes showed that the polymers with the longest R groups and lowest DMAA content were the most antimicrobial and hemolytic. This is in agreement with the biological activity of previously reported SMAMPs. Thus, the design concept of facial amphiphilicity has successfully been transferred, but the selectivity of these polymers for bacteria over mammalian cells still needs to be optimized.

Asymmetrically substituted poly(diitaconate) copolymers are synthesized from 1‐((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)‐4‐propyl diitaconate (PrIA) and different comonomers (N,N‐dimethyl‐acrylamide, DMAA; acrylic acid; or ((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)methacrylate) by reversible addition–fragmentation chain transfer polymerization (RAFT). The RAFT copolymerization parameters of PrIA and DMAA are rDMAA = 0.49 and rPrIA = 0.17, compared to rDMAA = 0.52 and rPrIA = 0.54 obtained by free radical copolymerization (FRP). Thus, the RAFT process has a stronger trend to alternating polymerization than the FRP process. The polydispersity index of the RAFT copolymers is around 1.2–1.8, compared to 2.8–2.9 for the corresponding FRP copolymers. After removal of the tert‐butoxycarbonyl protective groups, antimicrobially active synthetic mimics of antimicrobial peptides are obtained. The thus activated poly(PrIA‐co‐DMAA) copolymers (repeat unit ratio 1:1) have an increasing activity against Escherichia coli and Staphylococcus aureus with increasing molar mass. The RAFT copolymers are slightly more active and less toxic than comparable FRP polymers, leading to a higher selectivity for bacteria over mammalian cells. Higher molar fractions of PrIA in poly(PrIA‐co‐DMAA) copolymers (up to 80 mol%) do not increase their antimicrobial activity; reduction of the BuIA content in poly(BuIA‐DMAA) (down to 10 mol%) leads to a loss of activity against both E. coli and S. aureus.

Facially amphiphilic polymers carrying cationic and hydrophobic groups on the same repeat unit have shown promising antimicrobial activity and biocompatibility, yet they are prone to suffer from protein adhesion which may induce biofilm formation. To overcome this problem, poly(diitaconate)-based copolymers with cationic/hydrophobic and protein-repellent/charge-neutral repeat units are synthesized. The bioactivity profile of surface-attached polymer networks made from these copolymers depends on the ratio of the cationic and charge-neutral repeat units. In all cases, the protein adhesion is substantially reduced compared to purely cationic polymers. At a 50:50 ratio, the polymer coatings are partially protein-repellent and antimicrobial, yet slightly cell toxic. At an intermediate composition of 30:70, they are still antimicrobial and the cell compatibility is substantially improved. The long-term stability of these materials still has to be determined to judge their suitability for medical applications.