SYNTHESIS OF WATER-SOLUBLE POLYAMIDOAMINES FOR BIOMEDICAL APPLICATIONS .2. POLYMERS POSSESSING INTRACHAIN-TYPE SECONDARY AMINO-GROUPS SUITABLE FOR SIDE-CHAIN ATTACHMENT

As part of a program to synthesize water-soluble polymeric carriers su itable for drug binding, the polyaddition reaction of methylenebisacry lamide with comonomers containing two primary amino groups is investig ated. The copolymerization of the bisacrylamide with equimolar quantit ies of primary diamines under properly controlled experimental conditi ons is found to proceed in a linear propagation, giving rise to the fo rmation 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(ethyl ene glycol) of different chain length, the last three monomers being c hosen because of their outstanding hydrosolubilizing properties. Use o f two different diamines in the proper stoichiometry leads to correspo nding copolymers. The reactions are conducted in aqueous phase over pe riods of 1-3 days at 65-degrees-C, and the polymeric products, possess ing 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 possessi ng complete solubility in water. Inherent viscosities are in the range of 8-40 mL g-1. Microanalytical and spectroscopic data confirm the pr oposed structures. The suitability of the intrachain secondary amine f unctions for side chain attachment and drug coupling is demonstrated i n model reactions involving N-substitution. (C) 1993 John Wiley & Sons , Inc.