Theoretical Studies On Microscopic Mechanism Of The Deprotonation Of Radical Cation In Oxidized G-Quadruplex

The unique deprotonation characteristic of the G-quadruplex,provides the possibility for its wide application as a potential electronic device.At present,the incorporation of guanine analogues into G-quadruplex has become an important research topic.This thesis focuses on the microscopic process of deprotonation of the radical of GGX(8-oxo-G),the oxidized G-quadruplex double substituted by 8-oxoguanine(abbreviated as 8-oxo-G)and xanthine(abbreviated as X).The slower rate of deprotonation of GGX(8-oxo-G)is expected to become a more ideal proton transfer carrier than the duplex DNA structure and the G-quadruplex.It is necessary to established a theoretical model for the above system.Therefore,a multi-scale model,namely QM/MM(ABEEM),which is combined with the QM method and the ABEEM/MM fluctuating charge force field,is developed in this thesis to study the radical cation deprotonation process of the GGX(8-oxo-G).This thesis mainly includes the following two parts:(1)Quantum Mechanics(QM)was used to investigate the deprotonation of radical cation in the modified G-quadruplex.The GGX(8-oxo-G)was selected as the simplified model molecule.The deprotonation models of X·+,8-oxo-G·+,G1·+ and G2·+ with three water molecules were established.The M06-2X/6-31G(d)method was used to search the transition states of the above models in the gas phase,and IRC was obtained.The charge transfer of the above four reaction paths and the activation energy required for the deprotonation were calculated,and the most suitable deprotonation base was determined as X·+.(2)The QM/MM/(ABEEM)was developed,to explore the microscopic mechanism of the above reactions.Two types of local charge conservation conditions are set by the above four models:one is aimed at X·+ deprotonation model,the other is suitable for the deprotonation models of 8-oxo-G·+,G1·+ and G2·+.The relative ABEEM/MM parameters are optimized to fit the QM charge distributions.The linear correlations of the ABEEM charge distributions and QM charge distributions are all above 0.97 during the deprotonation process.Using the free energy perturbation scheme,the activation free energy of X·+ deprotonation of the GGX(8-oxo-G)is obtained(37.87 kJ/mol),which is consistent with the QM result(36.64 kJ/mol).