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Free radical scavenging potency of quercetin and its catecholic colonic metabolites: A DFT study

Flavonoids are thought to contribute to the beneficial health effects through diet rich in fruits and vegetables [1]. However, flavonoids generally have a low bioavailability (in nM range) suggesting that their bioactivity may be associated with their colonic metabolites which are present in systemic circulation at much higher concentrations (in micromolar range) [2]. Majority of ingested structurally diverse flavonoids (95%) undergo extensive colonic metabolism [3] producing the common set of simpler hydroxybenzoic acids and phenols [4]. Free radical scavenging potency of quercetin and its six catecholic colonic metabolites were studied in silico employing DFT approach as implemented in Gaussian 09 package [5]. Geometry optimizations and frequency calculations were carried out using the M05- 2X/6-311++G(d, p) level of theory, in conjunction with the SMD solvation model [6]. Two mechanisms of free radical scavenging reaction were considered: double hydrogen atom transfer (HAT) and double sequential proton loss electron transfer (SPLET). Obtained thermodynamic results indicate that all catecholic metabolites possess higher free radical scavenging potency than the parent quercetin molecule. They all have been found more potent scavengers than quercetin itself, able of deactivating various free radicals (HO•, HOO•, CH3O•, and CH2=CH–O–O•). Additionally, second HAT and SPLET processes have been estimated to be less energy demanding than the first ones indicating 2H+/2e– processes as inherent to catecholic moiety. Our results suggest that recently proposed complete abandonment of free radical scavenging as one of possible mechanisms contributing to the health benefits of polyphenols [7] appears to be premature. References: [1] D. Del Rio, A. Rodriguez-Mateos, J.P.E. Spencer, M. Tognolini, G. Borges, A. Crozier, Antioxid. Redox Signaling 18 (2013) 1818−1892. [2] M. Edwards, C. Czank, G.M. Woodward, A. Cassidy, C.D. Kay, J. Agric. Food Chem. 63 (2015) 2423−2431. [3] M.N. Clifford, Planta Med. 70 (2004) 1103−1114. [4] G. Williamson, C. Manach, Am. J. Clin. Nutr. 81 (2005) 243S−255S. [5] M.J. Frisch, G.W. Trucks, H.B. Schlegel et al., GAUSSIAN 09, Wallingford, CT, 2009. [6] P.C.H. Hollman, Arch. Biochem. Biophys. 559 (2014) 100−105. [7] M.E. Alberto, N. Russo, A. Grand, A. Galano, Phys. Chem. Chem. Phys. 15 (2013) 4642−4650.

quercetin ; metabolites ; radical scavenging ; DFT

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