Deprotonation Of Guanine Radical Cation In G-Quadruplex Using QM/ABEEM

The ability of DNA chains to transport positive charges（holes）has facilitated the research of molecular electronic devices in medical science.However,the rapid deprotonation of guanine radical cation（G·+）leads to the termination of the hole transport,and the rate of the deprotonation directly affects the efficiency of the transport.Exploring the microscopic reaction mechanism of the process can be an important adjunct to the design of medical electronic devices with DNA structures.A G-quadruplex has a higher efficiency of hole transport than the double-stranded DNA,making it a more ideal subject for the hole conduction research.In this thesis,we used the quantum chemistry（QM）method to study the deprotonation process of G·+ in G-quadruplex;and developed a multi-scale model,QM/ABEEM（MM）,which is the combination of QM and the atom-bond electronegativity equalization fluctuating charge molecular force field（ABEEM/MM）,to study the microscopic mechanism of the above process.The main content of this thesis is as follows:1.QM studies on the deprotonation of G·+ of G-quadruplexThe model systems were composed of a G-quartet,with one/two/three water molecules respectively.The QM calculations were performed at the M06-2X/6-31G（d）level,and results show that the G·+ deprotonation must proceed with at least three water molecules,so the 3H₂ O solvent model in the gas phase was determined as the system to be studied.The transition state was found and the deprotonation process was verified by the IRC,in which the deprotonated proton of the G·+ is transferred to another water molecule W2 via the water molecule W1,and finally generates H3O+,and the deprotonated product guanine neutral radical（G（-H）·）simutaneously.The charge transfers were studied and the activation energy for the deprotonation process is 20.8 k J/mol.2.Developing the QM/ABEEM（MM）,to explore the deprotonation of G·+ of G-quadruplexCompared with the traditional force field,the ABEEM/MM can reasonably represent the charge transfer of the system.We expressed the electronegativity of the valence state with a piecewise function to accurately describe the large fluctuations of the charge distribution along the reaction path.In this paper,the QM/ABEEM（MM）multi-scale model was developed and applied to investigate the deprotonation process of G·+ in the explicitambient solvent.Based on the charge distributions by the QM method,combining with the local charge conservation condition and the piecewise function of the valence stateelectronegativity,the ABEEM/MM parameters were fitted and optimized to achieve the charge transfers and the charge distributions consistent with those from the QM.The ABEEM charge distributions of each stagnation point along the IRC have a good consistency with those of the QM,and the linear correlation between them is above 0.97.Using this method combined with free energy perturbation,the activation free energy of the G·+ deprotonation is obtained by using the QM/ABEEM（MM）with the free energy perturbation scheme,and the result（20.7 k J/mol）is consistent with the experimental measurement（20 ± 1.0 k J/mol）.