CHARACTERIZATION AND NITRIC-OXIDE RELEASE STUDIES OF LIPOPHILIC 1-SUBSTITUTED DIAZEN-1-IUM-1,2-DIOLATES

Lipophilic esters of the naturally occurring polyamines putreanine and spermic acid were synthesized, characterized, and modified with nitri c oxide to form the corresponding 1-substituted diazen-1-ium-1,2-diola tes (previously known as NONOates). The resulting compounds were insol uble in water but were able to release nitric oxide (NO) when placed i n phosphate buffered saline (PBS) at physiological pH. The two categor ies of compounds examined were putreanate esters of cholesterol or hex adecanol, and spermate diesters of cholesterol or hexadecanol. The put reanate NONOate esters of cholesterol and hexadecanol had NO release h alf-lives of 60 h and 81 h, respectively while the spermate NONOate di esters of cholesterol and hexadecanol had NO release half-lives of 23 days and 7.1 days, respectively. The presence of 5% Tween 20 increased the half-life of the cholesteryl putreanate NONOate to 104 h but only slightly increased the half-life of the hexadecyl putreanate NONOate to 89 h. The 1% presence of the pharmaceutical lung surfactant Survant a did not significantly alter the half-life of NO release for the chol esteryl putreanate NONOate or for the hexadecyl spermeate NONOate, but the surfactant did increase the amount of NO release by 46% and 67% r espectively. (C) 1998 Elsevier Science B.V.