Alkyl esters of L-ascorbic acid: Stability, surface behaviour and interaction with phospholipid monolayers

L-ascorbic acid alkyl esters (ASC(n)) are molecules of pharmaceutical interest for their amphiphilic nature and proposed antioxidant power. In contrast to L-ascorbic acid, ASC(n) with different acyl chain lengths behaved stably upon oxidation and a tautomeric isomerization was observed. In Langmuir films, when the ascorbic ring has a negative charge, ASC(14) and ASC(16) form stable monolayers, contrary to ASC(10) and ASC(12). ASC(16) films showed transition from liquid-expanded (LE) to liquid-condensed phase, whereas ASC(14) showed only an LE phase. When ASC(n) are mainly neutral, ASC(14) showed phase transition from LE to a crystalline phase, as previously reported for ASC(16). The two-dimensional domains displayed crystal-like shapes with anisotropic optical activity when interacting with the polarized light under Brewster angle microscopy. The compounds with the longer acyl chain (ASC(16), ASC(14) and ASC(12)) exhibited good surface activity, forming Gibbs monolayers. They also were able to penetrate into phospholipid monolayers up to a critical point of 45-50 mN/m. The 1-palmitoy1-2-oleoylphosphatidylcholine/ASC(n) films showed LC and/or crystalline domains only for ASC(16). This study provides valuable-evidence regarding the stability and surface properties of this drug family, and casts light into the differential interaction of these drugs with lipid membranes, which is important for understanding its differential pharmacological activity. (C) 2015 Elsevier Inc. All rights reserved.