Molecular Modelling and Natural Polyphenol Compounds

Natural polyphenols  are antioxidants, i.e. they can (i) directly scavenge free radicals, (ii) inhibit lipid peroxidation, (iii) chelate metals, (iv) inhibit enzymes involved in oxidative stress and (v) stimulate the natural protective mechanisms.

The sheer free radical scavenging action is now well-understood. As lipid peroxidation inhibitior the mode of action of polyphenols is not only free radical scavenging but it also depends on the compound capacity to approach the lipid membrane. For example vitamin E (a reference lipid-peroxidation-inhibitor) is known to incorporate the lipid membrane. Thus lipophilicity is a chemical parameter crucial to favour this biological activity. We  demonstrated the importance of both parameters, i.e. HAT-capacity and lipophilicity (Trouillas et al. Journal of Physical Chemistry A, 2008, 112(5), 1054 – 1063; Calliste et al. Food Chemistry, 2009, in press). The first publication is a joint experimental and theoretical study that reports on a series of flavonolignans having different HAT-capacity and lipophilicity. The second reported on a natural lignan (argenteane) that has been isolated for the first time in our group and has appeared to be an effective lipid peroxidation inhibitor (as compared to quercetin and vitamin E). Again the quantum calculations helped to demonstrate that argenteane exhibits the perfect compromise between good redox capacity (for an effective free radical scavenging capacity) and good lipophilicity (for a good interaction with membranes).

Only a few studies reported on the location of polyphenols in membranes. Actually there are only indirect clues for some compounds. For example it is suggested that phenolic acid may act as free radical scavenger not inside the membrane but its vicinity. At the moment the partition coefficient log P is the only parameter used to estimate such an interaction with membranes. The present project aims at simulating the ability of different polyphenols (flavonoids, flavonolignans, lignans and phenolic acid) to approach the membrane. The use of molecular dynamic simulation may help to know the “exact” polyphenol location (either in the membrane, in the water phase, or the intermediate zone in between membrane and water phase).