Quantum Chemical Calculation Of Carbonate Radical Formation And Reaction Mechanism With Typical Biomolecules

Hydroxyl radicals are the most active species in reactive oxygen species（ROS）.ROS can cause DNA damage in organisms,which causes changes in DNA structure and function,thus damaging the stability of genetic information in DNA to varying degrees,and posing a potential threat to induce tumors.In recent years,it has been found that a large number of carbonate anion radicals（?CO₃^-）have been detected in solutions containing carbon dioxide.How hydroxyl radicals are converted into carbonate radicals and whether carbonate radicals react with the main structural components of DNA like hydroxyl radicals is worth further study.In this paper,the quantum chemical calculation of how hydroxyl radical is transformed into carbonate radical and the reaction mechanism between carbonate radical and guanine,the main structural component of DNA is studied.Firstly,density Functional theory（DFT）and Gaussian 09 software were used to calculate the reaction mechanism of hydroxyl radical conversion into carbonate anion radical in CO₂,HCO₃^-and H₂CO₃ system.All reactants,complexes,transition states and products in aqueous solution were geometrically optimized at the UM06-2X/aug-cc-p VTZ level using an implicit CPCM solvent model with two explicit water molecules.The transition states,complexes and products were identified by vibration frequency and intrinsic reaction coordinate（IRC）analysis.On this basis,UCCSD（T）-F12/cc-p VDZ-F12 method and base set are used to calculate the single point energy.The intrinsic reaction coordinates were calculated from the transition state and the reaction channels were confirmed.The reaction energy barrier,enthalpy change and free energy change of each elementary reaction in the reaction system were calculated.Finally,the reaction rate constant of the reaction process is calculated based on the partition function.The electrostatic potential（ESP）,mean local ionization energy（ALIE）,Fukui function（FF）and dual description（DD）of the van der Waals surface of guanine molecule were used to predict the radical reactivity at different positions of guanine molecule.The mechanism of the reaction of carbonate anion radical abstract hydrogen from different sites of guanine has been studied by using the continuum polarization aqueous implicit solvent model（CPCM）at the UB3LYP/6-31++G（d,P）level using density functional theory.The reaction energy barrier,enthalpy change,Gibbs free energy and reaction rate constant have been calculated.（1）All components containing CO₂（CO₂,HCO₃^-,H₂CO₃）,the energy barrier between hydroxyl radical and HCO₃^-was the lowest（5.6kcal/mol）and the rate constant was the largest(7.60×10⁷dm³mol^-1s^-1).The energy barrier was the highest（20.3kcal/mol）and the reaction rate constant was the lowest(8.88×10^-10dm³mol^-1s^-1).The reaction products of CO₂and H₂CO₃ with hydroxyl radical are?HCO₃.?CO₃^-is formed directly from the reaction of HCO₃^-with hydroxyl radical.（2）The?HCO₃ generated by the reaction of CO₂ and H₂CO₃ with hydroxyl radicals is further dissociated in aqueous solution to form carbonate anion radicals.The calculation of free energy of the dissociation process is-2.5kcal/mol,and the p Ka is-1.9,indicating that?HCO₃ is a strong acid.Therefore,hydroxyl radicals are spontaneously converted to carbonate anion radicals in CO₂-containing systems.（3）According to the reaction energy barrier and reaction rate of the reaction between HCO₃^-and hydroxyl radical to generate?CO₃^-,it can be seen that the reaction energy barrier required for the transformation of hydroxyl radical into CO₃^-is very low（5.6kcal/mol）and the reaction rate is relatively fast(7.60×10⁷dm³mol^-1s^-1).Considering the ratio of different ions in CO₂-containing systems,the mainly reaction of hydroxyl radicals with H₂CO₃ to form?HCO₃ and then ionize to form?CO₃^-.（4）The active sites of guanine were predicted by electrostatic potential,average local ionization energy,Fukui function and double descriptors.The results showed that electrostatic potential analysis,average local ionization energy,Fukui function and double descriptors showed good effects on the prediction of active sites of guanine free radicals.The predicted results showed high reactivity at the H16 and H15 sites of guanine N11. However,the C8 position H14 position has the lowest reactivity.（5）Based on the transition state theory（TST）,the reaction paths of hydrogen abstraction from different positions of guanine by carbonate anion radical were calculated.The results showed that the energy barrier of hydrogen abstraction from H16 of N11 position of guanine by carbonate anion radical was the lowest（4.87kcal/mol）and the free energy barrier was the lowest（7.14kcal/mol）,the reaction rate was the largest(2.05×10²⁸s^-1).（6）By predicting the reaction active sites of guanine molecule surface and the hydrogen abstraction reaction of carbonate anion radical with guanine,the results show that H16 on the amino group of guanine has higher hydrogen abstraction reaction activity compared with other positions,while H14 on C8 position is the least active position.The carbonate anion radical abstracted a hydrogen from the guanine molecule to form the neutral guanine radical and HCO₃^-.The subsequent reaction of guanine radicals is the main source of DNA damage.