Nitric oxide-releasing molecules
View Patent ↗This invention relates to compositions comprising carbon-based diazeniumdiolates that release nitric oxide (NO). The carbon-based diazeniumdiolated molecules release NO spontaneously under physiological conditions without subsequent nitrosamine formation. The present invention also relates to methods of preparing the carbon-based diazeniumdiolated molecules, compositions comprising such molecules, methods of using such compositions, and devices employing such molecule compositions.
1. A composition comprising a C-based diazeniumdiolate compound, wherein
said composition releases NO under physiological conditions in predictable and tunable quantities and does not generate nitrosamines under physiologic conditions, wherein said C-based diazeniumdiolate compound is represented by the formula:
R 3 —C(R 1 ) x (N 2 O 2 R 2 ) y I
wherein x is an integer from 0 to 2 and y is an integer from 1 to 3 and the sum of x plus y equals 3;
wherein R 1 is ether, thioether, amine, —NO 2 , or an electron-withdrawing group;
wherein R 2 is a countercation or a protecting group on the terminal oxygen;
wherein said protecting group is selected from the group consisting of aryl, glycosyl, acyl, alkyl and olefinic groups; wherein said alkyl group is selected from the group consisting of saturated alkyl, unsaturated alkyl, and functionalized alkyl; and wherein said functionalized alkyl is selected from the group consisting of 2-bromoethyl, 2-hydroxypropyl, 2-hydroxyethyl and S-acetyl-2-mercaptoethyl;
wherein R 3 is an aliphatic, aromatic or cycloalkyl group, wherein said aromatic group is phenyl wherein said phenyl group is unsubstituted or substituted with mono- or di-substituted amino, unsubstituted amino, ammonium, alkoxy, acetoxy, aryloxy, acetamide, aldehyde, benzyl, cyano, nitro, thiol, sulfonic, vinyl, carboxyl, nitroso, trihalosilane, trialkylsilane, trialkylsiloxane, trialkoxysilane, diazeniumdiolate, hydroxyl, halogen, trihalomethyl, ketone, benzyl or alkylthio; wherein said aromatic group is optionally a multi-ring system wherein the multi-ring system is selected from the group consisting of acridine, anthracene, benzazapine, benzodioxepin, benzothiadiazapine, carbazole, cinnoline, fluorescein, isoquinoline, naphthalene, phenanthrene, phenanthradine, phenazine, phthalazine, quinoline, and quinoxaline;
with the proviso that R 1 is not an imidate, thioimidate, amidine or enamine.
2. A composition according to claim 1 comprising a C-based diazeniumdiolate compound of the formula:
3. A composition according to claim 2 comprising a C-based diazeniumdiolate compound of the formula:
wherein R 2 is a counterion; and
wherein R 3 is substituted or unsubstituted phenyl.
4. The composition of claim 3 , wherein R 3 is a substituted phenyl group.
5. The composition of claim 4 , wherein R 3 is a 2,4-dinitrophenyl group.
6. The composition of claim 1 , wherein the ether is selected from the group consisting of —O(C 1 -C 6 )alkyl and —OSi(CH 3 ) 3 .
7. The composition of claim 1 , wherein the thioether is selected from the group consisting of —S(C 1 -C 6 )alkyl and —SPh, and wherein the Ph can be substituted or unsubstituted.
8. The composition of claim 1 , wherein the amine is a tertiary amine.
9. The composition of claim 8 , wherein the amine is —N(C 2 H 5 ) 2 .
10. The composition of claim 1 , 2 or claim 3 , wherein R 2 is a countercation selected from the group consisting of alkali metals, group IIa metals, transition metals, and group Ib elements.
11. The composition of claim 1 , 2 or claim 3 , wherein R 2 is a countercation selected from the group consisting of ammonium and other quaternary amines.