C-Terminal Functionalization of Nylon-3 Polymers: Effects of C-Terminal Groups on Antibacterial and Hemolytic Activities

Abstract

Nylon-3 polymers contain β-amino acid-derived subunits and can be viewed as higher homologues of poly(α-amino acids). This structural relationship raises the possibility that nylon-3 polymers offer a platform for development of new materials with a variety of biological activities, a prospect that has recently begun to receive experimental support. Nylon-3 homo- and copolymers can be prepared via anionic ring-opening polymerization of β-lactams, and use of an N-acyl-β-lactam as co-initiator in the polymerization reaction allows placement of a specific functional group, borne by the N-acyl-β-lactam, at the N-terminus of each polymer chain. Controlling the unit at the C-termini of nylon-3 polymer chains, however, has been problematic. Here we describe a strategy for specifying C-terminal functionality that is based on the polymerization mechanism. After the anionic ring-opening polymerization is complete we introduce a new β-lactam, approximately one equivalent relative to the expected number of polymer chains. Because the polymer chains bear a reactive imide group at their C-termini, this new β-lactam should become attached at this position. If the terminating β-lactam bears a distinctive functional group, that functionality should be affixed to most or all C-termini in the reaction mixture. We use the new technique to compare the impact of N- and C-terminal placement of a critical hydrophobic fragment on the biological activity profile of nylon-3 copolymers. The synthetic advance described here should prove to be generally useful for tailoring the properties of nylon-3 materials.

Controlling macromolecular structures towards effective antimicrobial polymers

“…Gellman at al. functionalized the N-and C-terminals of nylon-3 random copolymers (Table 4D) [100]. They found that there is a significant difference in the two types of polymer terminus in terms of introducing a hydrophobic group.…”

Physio-chemical and antibacterial characteristics of pressure spun nylon nanofibres embedded with functional silver nanoparticles

“…They have been also used in wound dressing and healing where these scaffolds possess more homogeneity, oxygen penetration and prevent infections and dehydration [8]. Nylon polymer nanofibres exhibit excellent mechanical properties, such as toughness, and high tensile strength and have been adopted to make various composites [9][10][11]. Ag nanoparticles show excellent antibacterial activity and have a tolerant range of cytotoxicity, strong inhibitory and bactericidal effects [12][13][14].…”

Functionally Diverse Nylon-3 Copolymers from Readily Accessible β-Lactams

“…4a,c,9,12 We used new β -lactams introduced above to explore the impact of the structure of the cationic subunit on the antibacterial activity of nylon-3 copolymers.…”