Thermodynamics of demethylation of polymethoxyflavones: implications for antioxidant and photoprotective activity

Naturally occurring polymethoxyflavone (PMF) compounds and their demethylated metabolites show numerous beneficial biological effects. However, reaction enthalpies describing O–C bond cleavage of methoxy OCH3 groups attached to flavonoid skeleton are still not available. In this work, we have theoretically studied O–C bond dissociation enthalpies of fourteen PMFs, as well as four (poly)methoxybenzenes, representing the model molecules, in gas-phase and methanol. Structural distinctions between PMFs result in a wide range of O–C BDEs, exceeding 60 and 70 kJ mol–1 in gas-phase and methanol, respectively. Electron abstraction from parent molecules affects bond dissociation enthalpies substantially. Considerable decrease was found for PMF•+ radical cations possessing more than two OCH3 groups in A ring of flavonoid skeleton. On the other hand, if only one or two OCH3 groups are attached to aromatic ring, an increase in bond dissociation enthalpies after electron transfer occurs. These trends corroborate with the results obtained for (poly)methoxybenzenes. In electronic excited state, demethylation is exothermic due to electron excitation energies larger than O–C bond dissociation enthalpies. Found results indicate that the demethylation of methoxy groups present in PMFs and naturally occurring (poly)phenols may contribute to their antioxidant and photoprotective effect.