Water‐Soluble polyamides as potential drug carriers. I. Poly(α,β‐D,L‐asparthydrazide‐CO‐D,L‐ornithine)

The polycondensation of d,l ‐aspartic acid with N δ ‐phthaloyl‐ l ‐ornithine in phosphoric acid at 185°C gives rise to the formation, in 60 — 75% yield, of random copolymers of the poly( d,l ‐succinimide‐ co ‐N δ ‐phthaloyl‐ D,L ‐ornithine) type 6 possessing inherent viscosities (DMF) in the range of 5 — 15 ml g −1 . Copolyimides of the same compositions 6 and comparable chain lengths are obtained from aspartic acid and the copper chelate of the phthaloylornithine. Treatment of copolymers 6 with hydrazine hydrate in DMF leads to N‐deprotection and opening of the intrachain succinimide rings with formation of hydrazide side groups. The resultant polyamides are of the poly(α,β‐ d,l ‐asparthydrazide‐ co‐d,l ‐ornithine) type 7 . Shorter reaction periods give incomplete hydrazinolytic ring opening, and the remaining succinimide units are cleaved hydrolytically during the subsequent aqueous workup, thereby transforming into aspartic acid units. The polyamides so formed possess the general poly(α,β‐ d,l ‐asparthydrazide‐co‐α,β‐ d,l ‐aspartic acid‐co‐ d,l ‐ornithine) structure 8 Both types 7 and 8 are soluble in water and, in this medium, give inherent viscosities of 5 — 14 ml g −1 . The potential drug‐anchoring capabilities of these amine‐functionalized polyamides are demonstrated by coupling reactions with model carboxylic acids.