Chart 1. Chemical structures of α-tocopherol, Trolox^®, and general structures of previously designed compounds, tetramethylchroman system is linked to the NO releasing moieties by adequate functionalities.¹⁰

Chart 2. General structures of the newly designed compounds: series d and e.

Scheme 1. Syntheses of nitrooxy-derivatives 7 and 8. Reagents and conditions: (a) AgNO₃, CH₃CN, rt, 72 h; (b) NH₂CH₃ (g), THF, rt; (c) CDI, CH₂Cl₂, rt, 24 h.

Scheme 2. Syntheses of nitrooxy-derivatives 10 and 12. Reagents and conditions: (a) i—CDI, THF, rt, 1 h; ii—NH₂NH₂·H₂O, THF, rt, 24 h; (b) 2-chloroacetylchloride, Et₃N, toluene, rt, 1 h; (c) i—4-nitrooxymethylbenzoic acid, CDI, CH₂Cl₂, rt, 1 h; ii—9; (d) AgNO₃, CH₃CN, rt, 168 h.

Scheme 3. Syntheses of nitrooxy-derivative 13 and furoxan derivatives 15 and 17. Reagents and conditions: (a) i—CDI, CH₂Cl₂, 1 h; ii—3-(nitrooxy)propanol or 14 or 16, rt, 24 h.

Figure 1. Molecular plot of 3-nitrooxypropyl 6-acetoxy-2,5,7,8-tetramethylchroman-2-carboxylate (20) showing the labeling of the non-H atoms and their displacement ellipsoids at the 50% probability level.

Figure 2. (a) Compounds 19, 20, 23, and24 aqueous concentration in presence of LDL (2.8 μM)/absence of LDL ratio. (b) Compound 23 aqueous, phosphate buffer, pH 7.4, solubility in absence and increasing amount of LDL. (c) clog P versus aqueous concentration with and without LDL ratio (the dotted line means tendency).

·NO releasing rate, vasorelaxation properties, and mammalian cytotoxicity of tested compounds

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·Vasorelaxation properties with and without ODQ

Lipophilicity data for α-tocopherol and hybrid compounds

Crystallographic and AM1/3-21G* optimized structure of compound 20