One of the main paradigms in Chemistry, coined in 1869 by Brown and Fraser, is that there is a relation between the chemical structure of a compound (C) and its biological activity (Φ): Φ=f(C).

This fits within the main paradigm in Pharmacology, namely that compounds do not act, unless bound (corpora non agit nisi fixata). Until now, over 1,000 manuscripts on the structure-activity relationship (SAR) of the antioxidant effect of flavonoids and relate phenolic compounds have been published. Nevertheless, the definitive SAR has not been found. 

In a pursuit of understanding of the biological activity of flavonoids, we studied the SAR for the peroxynitrite scavenging activity of a series of ‘simple’ mono phenolic compounds by combining experimental data with density functional theory (DFT) based quantum chemical calculation. The new perspective this revealed was that even within a group of structurally closely related compounds, different molecular mechanisms are involved in the antioxidant activity. 

This means that first the compounds that display the same molecular mechanism need to be grouped, and then subsequently within each group, a SAR might be constructed. In addition, other foreseeable challenges to come to a SAR for flavonoids, namely the deprotonation of the aromatic OH groups, the formation of intramolecular H-bridges and the solvent effect of water, should be considered.