Towards an improved prediction of the free radical scavenging potency of flavonoids: the significance of double PCET mechanisms.
The 1H(+)/1e(-) and 2H(+)/2e(-) proton-coupled electron transfer (PCET) processes of free radical scavenging by flavonoids were theoretically studied for aqueous and lipid environments using the PM6 and PM7 methods. The results reported here indicate that the significant contribution of the second PCET mechanism, resulting in the formation of a quinone/quinone methide, effectively discriminates the active from inactive flavonoids. The predictive potency of descriptors related to the energetics of second PCET mechanisms (the second O-H bond dissociation enthalpy (BDE2) related to hydrogen atom transfer (HAT) mechanism, and the second electron transfer enthalpy (ETE2) related to sequential proton loss electron transfer (SPLET) mechanism) are superior to the currently used indices, which are related to the first 1H(+)/1e(-) processes, and could serve as primary descriptors in development of the QSAR (quantitative structure-activity relationships) of flavonoids.
Department of Biology, The Josip Juraj Strossmayer University, Cara Hadrijana 8a, HR-31000 Osijek, Croatia.
Ana
A
Amić
Department of Chemical-Technological Sciences, State University of Novi Pazar, Vuka Karadžića bb, 36300 Novi Pazar, Serbia.
Zoran
Z
Marković
Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Jasmina M
JM
Dimitrić Marković
Division of Molecular Medicine, Rudjer Bošković Institute, P.O. Box 180, HR-10002 Zagreb, Croatia.
Višnja
V
Stepanić
NMR Center, Rudjer Bošković Institute, P.O. Box 180, HR-10002 Zagreb, Croatia.
Bono
B
Lučić
Faculty of Agriculture, The Josip Juraj Strossmayer University, Kralja Petra Svačića 1d, HR-31000 Osijek, Croatia. Electronic address: damic@pfos.hr.
Dragan
D
Amić
D004579:Electron Transport; D004583:Electrons; D005419:Flavonoids / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011522:Protons
D005419:Flavonoids; D016166:Free Radical Scavengers; D011522:Protons
BDE; Double PCET; ETE; Flavonoid; QSAR; Radical scavenging