Abstract
A polyester composed of spermic acid and 1,4-butanediol was synthesized via a Michael-type reaction, using 1,4-diaminobutane and 1,4-butanediol diacrylate. A linear polymer, poly(butanediol spermate), with Mw of 3,000 and a molecular weight distribution of 1.95, was insoluble in organic solvents, but slowly dissolved in water. After dissolving in water poly(butanediol spermate) hydrolyzed to produce spermic acid and 1,4-butanediol. The rate of hydrolysis was pH-dependent. At 20°C in buffers of pH 9.7, 7.4, and 4.8, 50% decomposition occurred in 2.5, 1.5, and 3.5 hours, respectively. Secondary amines in the polymer were chemically modified (34-45%) with nitric oxide to form 1-substituted diazen-1-ium-1,2-diolates which spontaneously released nitric oxide in neutral or acidic aqueous solutions. The poly(butanediol spermate) diazeniumdiolate, in pH 7.4 buffer at 37°C, slowly dissolved and hydrolyzed with a 50% hydrolysis in 190 hours. Nitric oxide release from the polymer was delayed for approximately 100 hours then given a first order release of nitric oxide with a half-life of 110 hours. In contrast, at pH 5.0 and 37°C, the poly(butanediol spermate) diazeniumdiolate slowly dissolved but immediately released nitric oxide with a half-life of 180 hours, and 50% hydrolysis time for polymer of 520 hours. Poly(butanediol spermate) diazeniumdiolate is potentially useful for site-specific nitric oxide delivery with subsequent hydrolysis of polymer to natural products when used in mildly acidic to neutral conditions.