Coupling of Cyclic and High-Polymeric [(Aminoaryl)oxy]phosphazenes to Carboxylic Acids: Prototypes for Bioactive Polymers

Prototypical polymer-bound chemotherapeutic or herbicidal systems have been synthesized in which bioactive molecules are linked to poly(organophosphazenes) by peptide-coupling techniques. The synthetic procedures were developed first through the use of cyclotriphosphazene small-molecule model systems and with the initial use of simple nonbioactive carboxylic acids. These reactions were then utilized for the synthesis of high-polymeric analogues containing bioactive side groups. The sodium salts of 4-cyanophenol and phenol were allowed to react with (NPCl₂)₃ or (NPCl₂)_n to yield derivatives of type [NP(OPh)_x-(OC₆H₄CN)_y]_{3 or n}. The 4-cyano groups were then reduced to 4-(aminomethyl)phenoxy units with the use of BH₃·THF. Condensation of the pendent amino groups with acetic, propionic, benzoic, acrylic, and nicotinic acids, N-acetylglycine, N-acetyl-DL-penicillamine, p-(dipropylsulfamoyl)benzoic acid, and 2,4-dichlorophen-oxyacetic acid was accomplished with the use of dicyclohexylcarbodiimide. The physical and chemical properties of the products are discussed.