Ultrafast Excited State Dynamics Of DNA Aza-nucleobases And Derivatives

Azabases represent an important family of DNA/RNA nucleobases derivatives.Usually,substitution of a carbon atom with a nitrogen atom at certain position in the canonical nucleobases would produce azabases.Azabases usually possess interesting and special photochemical properties,which makes them have a great potential application in the field of biology or medicine.Moreover,some kind of azabases have useful properties as antiviral and anticancer drugs and in the clinical treatment of several diseases even like cancer.However,the photosensitivity of azabases has also been reported and the related investigations are still lack.Therefore,in this thesis,we select a serious of azabases including their derivatives and analogues,using time-resolved spectral techniques to study their excited state dynamics.The investigation is expected to uncover the influence of nitrogen substitution on the excited state properties and provide more fundamental information for azabases to the related researchers.In the investigation,three kinds of azabases derivatives and analogues were comprehensively investigated by the steady state absorption and emission spectra,femtosecond time-resolved transient absorption spectra and femtosecond time-resolved fluorescence up-conversion spectra.For each kind,the corresponding relaxation mechanisms were proposed.Both primidine and purine azabases are investigated.In detail,5-azacytosine,8-azaadenine are typical azabases and N6-methyladenine possess important biological relavance as biomarkers for RNA methylation.Thus,the selected molecules could provide a more comprehensive understanding about the photophyscial and photochemical properties of azabases.The first kind of azabases investigated in this thesis are azacytosine derivatives including 5-azacytosine?5-AC?,2,4-diamino-1,3,5-triazine?2,4-DT?and 2-diamino-1,3,5-triazine?2-AT?.Although these three molecules share a quite similar structure with each other,their excited state dynamics are totally different.Based on the current transient absorption and TDDFT calculation results,we find that there are two nonradiative relaxation pathways in 5-AC.The initial populated S₂???*?state in 5-AC could relax to the low-lying S₁?n?*?state or directly to the ground state with the lifetimes of 15 ps and 1.5 ps respectively.2,4-DT only possesses a single relaxation pathway to the ground state with the lifetime of 17 ps.In 2-AT,we only find a 2.6 ps nonradiative relaxation pathway for S₃???*?to relax to the low-lying n?*state.In general,the lifetimes of the excited azacytosine derivatives are significantly longer than that of cytosine.We proposed that the nitrogen substitution on the C5 position would hinder the torsion of N5=C6 bond which is associated with the conical intersection in the??*state,and finally lead to a longer excited state lifetime.Additionally,the introduction of an extra nitrogen atom will increase the possibility of low-lying dark n?*state existence,which eventually drives a more complicated relaxation mechanism in azabases.The second kind of azabases investigated in this thesis are azapurine derivatives.We comprehensively investigated the excited state dynamics of 8-azaadenine?8-AA?in both neutral and deprotonated forms.The pH-controlled intersystem crossing?ISC?was found in 8-AA.When the solution pH is lower than 6.3,8-AA exists in its neutral form.Then significant ISC process can be observed during the relaxation with the lifetime of 160 ps.The lifetime of the triplet state was further determined to be 6.1 us.When dissolved in a pH>6.3 solution,8-AA exists in its deprotonated form.Under such circumstance,the efficient internal conversion is dominant and the lifetime was determined to be 10 ps.The pH-controlled intersystem crossing could further lead to the pH-controlled singlet oxygen generation.The singlet oxygen yields were measured to be 13.8%and 1.8%for neutral and deprotonated 8-AA respectively.We proposed two plausible explanations for the pH-controlled excited state dynamics in 8-AA.?1?The hydrogen at N9 position could change the potential energy surfaces on the S₂???*?state and S₁?n?*?state,which further affect the possibility through the CI and eventually lead to a different relaxation mechanism.?2?The weaker spin orbital coupling between S₁?n?*?state and T₁???*?state in deprotonated 8-AA hinder the intersystem crossing and also lead to a different relaxation mechanism.The third kind of azabases derivatives investigated in this thesis are N6-methyladenine?6MeAde?and N6-methyladenosine?6MeAdo?.Femtosecond time-resolved transient absorption measurement,fluorescence up-conversion measurement and kinetic isotopic effect experiment were performed on both 6MeAde and 6MeAdo to uncover their excited state dynamics.Significant dual emission can be observed in6MeAde and are assigned to the emission from both local excited?LE?state and intramolecular charge transfer state?ICT?.The lifetimes of??*?L_a?state,??*?L_b?state and ICT state were determined to be 0.3 ps,1.6 ps and 107 ps respectively.In 6MeAdo,the ICT state was effectively quenched and the lifetime of??*?L_a?and??*?L_b?state were determined to be 0.56 ps and 3.0 ps.Based on the kinetic isotopic effect and solvation experiments,we also found that the H-bonding with solvent could affect the nonradiative decay rate of the ICT state in 6MeAde.Additionally,we proposed two plausible explanations for the ICT state quenching in 6MeAdo.?1?The ribose group addition at N9 position could lower the energy of LE state and eventually quench the ICT state.?2?The ribose group addition could weaken the H-bonding between electron acceptor and solvent and might also quench the ICT state.In this thesis,we investigated the excited state dynamics of three kinds of azabases derivatives and analogues using femtosecond time-resolved techniques.It's our hope that this investigation will improve the understanding of structure in regulating the excited state dynamics in azabases and provide more fundamental information for their potential application in biology and medicine.