Simulation of oleuropein structural conformation in vacuum, water and triolein–water systems using molecular dynamics

Oleuropein, the main phenolic compound of olive leaves, exhibits a unique blend of biological activities and has been shown to locate itself at the oil–water (O/W) interface. This behavior could influence the physico-chemical properties of dispersed systems such as emulsions. In this work, we study the effect of the microenvironment (vacuum, water, and triolein–water) on the conformational preferences of oleuropein using molecular dynamics (MD) simulations at 300 K for at least 30 ns. The seven torsions that describe the flexible skeleton of oleuropein were monitored together with the distance between the glucose (Glu) and hydroxytyrosol (Hyd) moieties (dglu–hyd) of the molecule. The obtained trajectories demonstrated that oleuropein adopts different conformations that depend on the environment. The preferential conformers in each system were analyzed for their molecular geometry and internal energy. In vacuum, the oleuropein preferential conformation is tight with the glucose moiety in close proximity with the hydroxytyrosol moiety. In water, oleuropein preferential conformers presented large differences in their structural properties, varying from a close like U form, and a semi-opened form, to an opened form characterized by high fluctuations in dglu–hyd values. In a triolein–water system, oleuropein tends to adopt a more open form where the glucose moiety could be approximately aligned with the hydroxytyrosol and elenolic acid moieties. Based on a calculation at the HF/6-31G* level, these flexibilities of oleuropein required energy of 19.14 kcal/mol in order to adopt the conformation between water and triolein–water system. A radial distribution function (RDF) analysis showed that specific hydroxyl groups of Hyd and Glu interact with water molecules, enabling us to understand the amphiphilic character of oleuropein at the triolein–water interface. MD calculations together with interfacial tension measurements revealed that the oleuropein binding at O/W interface is an enthalpy driven mechanism.