Synthesis of water‐soluble polyamidoamines for biomedical applications. II. Polymers possessing intrachain‐type secondary amino groups suitable for side‐chain attachment

As part of a program to synthesize water‐soluble polymeric carriers suitable for drug binding, the polyaddition reaction of methylenebisacrylamide with comonomers containing two pri‐mary amino groups is investigated. The copolymerization of the bisacrylamide with equi‐molar quantities of primary diamines under properly controlled experimental conditions is found to proceed in a linear propagation, giving rise to the formation of polyamides comprising two or more secondary amino groups in the recurring unit. Selected diamine monomers include ethylenediamine, diethylenetriamine, triethylenetetramine, 1,2‐bis (3‐aminopropylamino) ethane, and three 0,0´‐bis‐(2‐aminopropyl) derivatives of poly(ethylene glycol) of different chain length, the last three monomers being chosen because of their outstanding hydrosolubilizing properties. Use of two different diamines in the proper stoi‐chiometry leads to corresponding copolymers. The reactions are conducted in aqueous phase over periods of 1–3 days at 65°C, and the polymeric products, possessing the linear polyamidoamine structures 1 and 2, are fractionated by dialysis in membrane tubing with 12000–14000 molecular‐mass cutoff and are isolated by freeze‐drying as solid or resinous materials possessing complete solubility in water. Inherent viscosities are in the range of 8– 40mLg‐1. Microanalytical and spectroscopic data confirm the proposed structures. The suitability of the intrachain secondary amine functions for side chain attachment and drug coupling is demonstrated in model reactions involving N‐substitution.