title: Elucidation of the mechanistic pathways of the hydroxyl radical scavenging reaction by daidzein using hybrid QM/MM dynamics.
abstract: Employing a hybrid QM/MM simulation we  explored the reaction dynamics of the hydroxyl radical scavenging activity of daidzein, a soy isoflavone. Our simulations illustrate that the highly reactive hydroxyl radical can participate in hydrogen abstraction reaction with both  OH functional groups of daidzein and can form stable daidzein radicals. We found that the reaction involving the 4'-OH site of daidzein is energetically favorable over the other reaction pathway involving the 7-OH site of daidzein by ∼29 kcal/mol. The high enthalpic stabilization involved in  daidzein radical formation at the 4'-OH site can be partly attributed to better solvation through hydrogen-bonding interactions with water and higher electron density delocalization of radical over the adjacent aromatic ring. As evident from the QM/MM dynamics, both  HAT pathways led to  formation of ketones at the 7-OH and 4'-OH sites of daidzein, respectively, and the adjacent aromatic rings appear in a p-quinonoid form, a highly stable resonating structure. The suitability of the QM/MM methodology to study the reaction mechanism, identification of intermediate states, and pathways of flavonoid radical stabilization reported here opens up a new possibility to study a similar reaction mechanism in other systems.
authors.affiliation: Laboratory of Computational Biophysics & Bioengineering Department of Physics, Tougaloo College, Tougaloo Mississippi 39174, United States.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Chakraborty
authors.forename: P K
authors.initials: PK
authors.lastname: Biswas
mesh_terms: D016166:Free Radical Scavengers / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D007529:Isoflavones / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D016166:Free Radical Scavengers; D007529:Isoflavones; D014867:Water; D017665:Hydroxyl Radical; C004742:daidzein