Synthesis of random terpolymers and determination of reactivity ratios of N‐carboxyanhydrides of leucine, β‐benzyl aspartate, and valine

The copolymerization and terpolymerization of leucine‐N‐carboxyanhydride, β‐benzyl aspartate‐ N‐carboxyanhydride, and valine‐N‐carboxyanhydride in dioxane, initiated with triethylamine, were investigated to determine the random nature of the terpolymer composition for potential applications as targeting drug delivery carriers. 1H NMR was used to obtain the actual monomer compositions of the polymers. The reactivity ratio of each monomer was determined with Fineman–Ross, Kelen–Tüdös, and nonlinear least‐squares curve‐ fitting methods. The product of the estimated reactivity ratios from the monomers in the binary copolymerizations indicated that random polymers were predominantly formed. On the basis of the reactivity ratios determined from the binary copolymers, Alfrey–Goldfinger equations were used to estimate the compositions of the terpolymers. There was no statistical difference between the actual monomer compositions and the calculated compositions of the terpolymers; this validated the reactivity ratios estimated by Fineman–Ross, Kelen–Tüdös, and nonlinear least‐squares curve‐ fitting methods. Therefore, the poly(leucine‐β‐Bzl‐ aspartate‐valine) synthesized in this study was primarily a random terpolymer.