Exploring the influence of acetylenic acetogenin unsaturation patterns on lipid interface interactions: Insights from surface chemistry, rheology, and spectroscopy

Abstract

This study explores how the unsaturation patterns of three acetogenins from Porcelia macrocarpa (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11′-yn-19′-enyl)-butanolide (1), (2S,3R,4R)-3-hydroxy-4-methyl-2-(eicos-11′-ynyl)-butanolide (2), and (2S,3R,4R)-3-hydroxy-4-methyl-2-eicosyl-butanolide (3)—affect their interactions with lipid interfaces, using Langmuir monolayers of dipalmitoyl-phosphoethanolamine (DPPE) as a model for protozoal membranes. The hypothesis posits that unsaturated acetogenins (1 and 2) will exhibit distinct behaviors compared to the saturated acetogenin (3) due to structural differences. Experiments incorporated each acetogenin into DPPE monolayers, employing techniques like tensiometry, dilatational rheology, infrared spectroscopy, and Brewster angle microscopy (BAM) to assess interactions and changes in film properties. Results showed that unsaturated acetogenin 1, active against Leishmania infantum and Trypanosoma cruzi, destabilized the film and induced rapid molecular reorganization, while acetogenin 2, inactive against these parasites, uniquely increased the viscous contribution to viscoelasticity. Saturated acetogenin 3 did not integrate into the film. All acetogenins enhanced fluidity, reducing elasticity and viscosity, with BAM revealing phase separation only in acetogenin 2. Infrared spectroscopy underscored the impact of drug-lipid interactions, leading to the conclusion that unsaturated acetogenins 1 and 2 have a more significant influence on thermodynamic and structural properties than acetogenin 3, offering insights into their potential therapeutic mechanisms.

Keywords

• Tensiometry
• Langmuir monolayers
• Cell membranes models
• Air-water interface