Theoretical Studies On The Proton Transfer Mechanism And Radiosensitivity Of Artificial Bases

Recently,the successful incorporation of artificial base pairs in genetics has made a significant progress in synthetic biology.The research on the related structure and properties of artificial bases plays a vital role in exploring possible multi-composition and multi-morphological life forms and expanding the information storage capacity of DNA molecules.In 2019,Benner and collaborators found that newly synthesized artificial bases(ZP and BS)can recognize and bind to each other like natural bases,and form a self-sustaining and stable double helix structure.Relevant studies have pointed out that the introduction of artificial bases can greatly increase the information storage capacity of DNA molecules.In addition,it has also been found that DNA strands containing artificial ZP base pairs could better combine with breast cancer cells and thus can be transformed into"cancer cell hunters".Therefore,new artificial bases have broad application prospects in biotechnology,and the research on the related properties and dynamics is of great significance in the fields of information,biology and medicine.On the basis of the mentioned above,this work systematically explored the intermolecular proton transfer mechanism and photoisomerization process of the artificial bases ZP by calculating the geometric configuration,potential energy surfaces,absorption spectrum and frontier molecular orbital.In addition,based on the halogenated artificial bases,the electron affinity energies,the anion dissociation potential energy curves and the dissociation processes controlled by the nitro group were studied to clarify the radiosensitization mechanism of the system.1.Theoretical study on the intermolecular proton transfer mechanism and nitro rotation tuned photoisomerization of artificial base pair-ZPFirst,we constructed the relaxed potential energy surfaces(PESs)of the ground(S₀)and the first excited(S₁)states in both gas phase and solution based on density functional theory(DFT)and time-dependent density theory(TDDFT).The correlation results show that the double proton transfer(DPT)in the gas phase follows a concerted mechanism,and the excited state hydrogen bond strengthening mechanism promotes the reaction in the S₁state.In addition,we further consider the solvent effect on the process by introducing the PCM model and the explicit solvent molecules(5 H₂O molecules).The calculation results show that the solvent effect can promote the single proton transfer process by stabilizing the product and reducing the reaction barriers.In contrast to the related proton transfer channel of the natural bases,there is no conical intersection between S₀and S₁states of the ZP base pair,so ZP has a longer lifetime in the S₁state and possesses weaker photostability than that of natural base pair.Finally,we characterized the molecular vibration effect on the electronic properties and revealed the electronic excitation can be tuned by the rotation of nitro group.2.Density functional theory study on the radiosensitizing properties of halogenated Z-baseThe dissociation potential energy curves of Z-base substituted with different halogens(F,Cl,Br,I)before and after electron attachment were calculated by DFT to clarify their radiosensitization properties.First,the geometric structures of halogenated Z-base were optimized,and the electron affinity of Z-base and halogenated Z-base were calculated.The calculation results show that the electron affinity of artificial Z-base is much higher than that of natural base U,and halogenated Z-base has an exceptionally electron affinity,especially 4Br Z and 4IZ,which indicates its strong attraction to the excess electrons in the environment.By constructing the dissociation potential energy curves of neutral molecule and anion radical of halogenated Z-base,the potential barrier of dissociation reaction can be expressed intuitively.The results show that 4Br Z and 4IZ are more prone to dissociation reactions to generate halogen anions and Z?base radicals,which further damage DNA molecules.Finally,we characterized the regulatory role of the nitro group on the Z-base in the dissociation process.In addition,considering that the ZP base pair proposed by the predecessors is more likely to bind to cancer cells,this further reveals the importance of 4Br Z and 4IZ as radiosensitizers.This thesis is divided into five chapters.The first chapter is an introduction,which mainly introduces the artificial bases,radiosensitizers,related photochemical and photophysical processes.The second chapter is the theoretical method,which mainly introduces the relevant knowledge of density functional theory and time-dependent density functional theory.The third chapter studies the proton transfer mechanism and nitro rotation tuned photoisomerization of artificial base pair-ZP.The forth chapter investigates the radiosensitizing properties of artificial base-Z.The last chapter summarizes the work done and the innovative points of the article,and makes an outlook for future research directions.