Kinetics of Anionic Ring-Opening Polymerization of Variously Substituted β-Lactams: Homopolymerization and Copolymerization

Nylon-3 copolymers generated via ring-opening polymerization of β-lactams have recently been shown to function as selective antibacterial agents or as chemoattractants that can induce fibroblasts to attach to surfaces. Understanding the molecular basis of these activities and developing improved materials requires knowledge of the relative reactivities of different β-lactams, which influence subunit distribution patterns within polymer chains. The homopolymerization of a cyclooctyl β-lactam ( 2 ) in the presence of a strong base and imide co-initiator was studied using both gas chromatography (GC) and in situ infrared (IR) spectroscopy. The rate of this anionic ring-opening polymerization reaction exhibits a first-order dependence on the β-lactam and co-initiator concentrations and a zero-order dependence on the base concentration. Analogous studies of four other β-lactams, bearing various substituents [cyclohexyl ( 1 ), cyclododecyl ( 3 ), and Boc-protected amino groups ( 4, 5 )], revealed that different monomers exhibit significantly different homopolymerization rates. Binary copolymerizations of four β-lactam pairs ( 1 + 4, 2 + 3, 2 + 4, and 2 + 5 ), several of which lead to biologically active amphiphilic copolymers, were investigated by GC. In each of the copolymerizations, except for 2 + 3, the two β-lactams were consumed at different rates, leading to compositional drift within the resulting polymers (i.e., variable subunit distribution along the length of the polymer chains). The copolymerization rates of 2 + 3 and 2 + 4 exhibited a monotonic dependence on the starting β-lactam composition, whereas the copolymerization of 1 + 4 and 2 + 5 was slower than either of the respective β-lactam homopolymerizations. Three methods (Fineman−Ross, Kelen−Tudos, and Mayo−Lewis) were employed to determine the reactivity ratios of these β-lactam pairs at low conversions. This analysis confirms that the copolymers obtained from 1 + 4, 2 + 4, or 2 + 5 are characterized by some extent of compositional drift, while poly( 2 + 3 ) is an ideally random copolymer. These results provide valuable insights pertinent to the molecular structure of amphiphilic nylon-3 copolymers that exhibit bioactivity.