Asymmetrically Substituted Poly(diitaconates) Obtained by Reversible Addition‐Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis, Copolymerization Parameters, and Antimicrobial Activity

Abstract

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.

Antimicrobial Polymers of Linear and Bottlebrush Architecture: Probing the Membrane Interaction and Physicochemical Properties

“…[18,19] In addition to the amphiphilic balance, other interconnected properties that may affect the antimicrobial activity, as well as the toxicity profile of the APs, must be carefully considered in the structure design. Among others, the molecular weight, [20] the dispersity, [21] the nature of the cationic unit, [18,22] the spacial organization of subunits, [23,24] the properties of the end group, [21,25] the monomer sequence, [26,27] and the chain architecture [28][29][30][31] play a role.…”

Progress in the Free and Controlled Radical Homo‐ and Co‐Polymerization of Itaconic Acid Derivatives: Toward Functional Polymers with Controlled Molar Mass Distribution and Architecture

“…[ 153 ] RAFT‐polymerized itaconic acid derivatives have also been used as platform for antimicrobial polymers. [ 11,154,155 ] The thus obtained asymmetrically substituted poly(diitaconate) copolymers with one hydrophobic and one cationic group per diitaconate repeat unit showed promising antimicrobial activity, yet were not yet sufficiently cell compatible to be used as antimicrobial drugs. [ 11 ]…”

“…[ 9 ] Further substitution yields diitaconates or diitaconamides (Figure 1d) with either two identical or two different R groups. [ 10,11 ] Disubstituted derivatives of itaconic acid with different substituents are particularly interesting, as they yield polymers with a built‐in, locally precisely balanced stoichiometry of the two functional groups. Such polymers are not accessible by co‐polymerization of acrylic or methacrylic monomers due to the statistical nature of these polymerizations.…”

“…In the biomedical field, monosubstituted itaconamides carrying one ammonium group are an interesting synthetic platform for bioactive poly(carboxyzwitterions), [ 9 ] and asymmetrically substituted diitaconates with one hydrophilic and one hydrophobic group per monomer give access to amphiphilic polymers with tunable antimicrobial activity. [ 10,11 ]…”

Trendbericht: Makromolekulare Chemie

“…Auf Basis dieser Syntheseroute sollen antimikrobielle Wirkstoffe als Antibiotikaalternativen und antimikrobielle Beschichtungen für Medizinprodukte entwickelt werden. 5) Auch bei Hydrogelmaterialien ist Nachhaltigkeit wichtig, was Liedel und Mitarbeiter aufgriffen. Durch Polykondensation erstellten sie flexible Polyelektrolytnetzwerke mit vielen positiven Ladungen im Polymerrückgrat.…”