Interactions of chlorogenic acid and isochlorogenic acid A with model lipid bilayer membranes: Insights from molecular dynamics simulations.

Because of the negative side-effects of synthetic preservatives, the naturally-occurring polyphenols aroused intense interest of researchers. It has been suggested that chlorogenic acid (CA) and isochlorogenic acid A (iso-CAA) were good candidates to replace the synthetic preservatives. Moreover, the bactericidal activity of iso-CAA was stronger than CA, and the anti-bacterial activities of iso-CAA and CA were highly membrane-dependent. However, the mechanisms were still unclear. Therefore, in the present study, we investigated the mechanisms of the interactions between the two polyphenols and lipid bilayers through molecular dynamics simulations. The results revealed that iso-CAA could be inserted much deeper into POPG lipid bilayer than CA. We also found that hydrophobic interactions and hydrogen bonds both contributed to the insertion of iso-CAA into the POPG lipid bilayer, and the quinic acid moiety was the key structure in iso-CAA to form hydrogen bonds with POPG lipid bilayer. We believed that these findings would provide more useful information to explain the stronger bactericidal activity of iso-CAA than CA at the atomic level.

Influence of the gallate moiety on the interactions between green tea polyphenols and lipid membranes elucidated by molecular dynamics simulations.

Previous studies suggested that naturally occurring EGCG primarily acted on the bacterial cell membrane then damaged the membrane and the gallate moiety in EGCG was very important to its anti-bacterial activity. However, the detailed mechanisms were still poorly understood. In this paper, EGCG and EGC were selected to study the great contribution of gallate moiety on the anti-bacterial activities of polyphenols. The results indicated that EGCG could penetrate deeper into the POPG lipid bilayer and possess more potent structure-perturbing potency on the POPG lipid bilayer than EGC. We also found that EGCG had the ability to form hydrogen bonds with the deeper inside oxygen atoms in the POPG lipid bilayer and the gallate moiety was the key functional group for EGCG forming hydrogen bonds with the POPG lipid bilayer. Moreover, results from the binding free energy analysis demonstrated that the gallate moiety made great contribution to the high affinity between EGCG and the POPG lipid bilayer. We believed that these findings could yield useful insights into the influence mechanisms of gallate moiety on the anti-bacterial activities of polyphenols.