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 nitric oxide to form the corresponding 1-substituted diazen-1-ium-1,2-diolates (previously known as NONOates). The resulting compounds were insoluble in water but were able to release nitric oxide (NO) when placed in phosphate buffered saline (PBS) at physiological pH. The two categories of compounds examined were putreanate esters of cholesterol or hexadecanol, and spermate diesters of cholesterol or hexadecanol. The putreanate NONOate esters of cholesterol and hexadecanol had NO release half-lives of 60 h and 81 h, respectively while the spermate NONOate diesters of cholesterol and hexadecanol and 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 Survanta did not significantly alter the half-life of NO release for the cholesteryl putreanate NONOate or for the hexadecyl spermeate NONOate, but the surfactant did increase the amount of NO release by 46% and 67% respectively.