Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/18/2011
Publication Date: 3/18/2011
Publication URL: DOI: 10.1021/jf2006547
Citation: Sirk, T.W., Friedman, M., Brown, E.F. 2011. Molecular binding of black tea theaflavins to biological membranes: relationship to bioactivities. Journal of Agricultural and Food Chemistry. 59:3780-3787. Interpretive Summary: Interest in theaflavins, which impart the black color to black teas, arises from the fact that they are reported to exhibit numerous health-related beneficial effects, including antibacterial, antifungal, antiviral, and antiotixin activities. One mechanism by which theaflavins operate at the cellular-molecular level involves interaction with components of cell membranes leading to disruption of the membranes resulting in leakage of cell components followed by cell death. Large differences in biological activities of structurally different theaflavins may to be due to differences in relative affinities to lipid and glycoprotein layers of cell membranes. In this study, we investigated by means of molecular dynamics simulations with the aid of mathematical tools and advanced computer programs, the chemical basis for these interactions. The results indicate that hydrogen bonding of phenolic hydroxyl groups to lipid bilayers of cell membranes may govern the mechanism of antimicrobial and other beneficial effects. The described modeling approach complements our two related published studies on green tea catechins. The results contribute to our understanding of the mechanism of bioactivities of phenolic compounds at the molecular and cellular levels and may make it possible to predict relative bioactivities of structurally different tea ingredients.
Technical Abstract: Molecular dynamics simulations were used to study the interactions of three theaflavin compounds with lipid bilayers. Experimental studies have linked theaflavins to beneficial health effects, some of which are related to interactions with the cell membrane. The molecular interaction of theaflavins with membranes was explored by simulating the interactions of three theaflavin molecules (theaflavin, theaflavin-3-gallate, and theaflavin-3,3’-digallate) with a mixed bilayer composed of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE). The simulations show that the theaflavins evaluated have an affinity for the lipid bilayer surface via hydrogen bonding. The molecular structure of theaflavins influenced their configuration when binding to the bilayer surface, as well as their ability to form hydrogen bonds with the lipid headgroups. The theaflavin-bilayer interactions studied here help to define structure-function relationships of the theaflavins, and provide a better understanding of the role of theaflavins in biological processes. The significance of the results for relation of black tea composition to bioactivity is discussed.