Ultrafast Excited State Dynamics In Epigenetic DNA From Nucleoside To Duplex

Epigenetics refers to the change of phenotype of an organism caused by the change in gene expression without changing the gene sequence.The significances of epigenetics include growth and development,aging and diseases.Epigenetic nucleosides in DNA are important mutation sites for many diseases,such as skin cancer induced by ultraviolet radiations.Epigenetic modification may undermine the photostability of DNA but related investigations are still scarce.In this thesis,we investigate the excited state dynamics of epigenetic nucleic acid derivatives using ultrafast time-resolved spectroscopy combined with high-level theoretical calculation.This study is expected to provide the theoretical basis for future studies on how epigenetic modifications change the photostability of DNA.First,we revisited the excited state relaxation of 2'-deoxycytidine(dCyd) and 2'-deoxy-5-methylcytidine(5mdCyd).By varying the excitation wavelength,solvent and pH,we found that there are two distinct decay pathways in dCyd and 5mdCyd when the molecules are initially photoexcited to different optically bright states(??*₁ and ??*₂ state).When the higher energy??*₂ state is populated,the excited state population relaxes to the??*₁ state within hundreds of femtoseconds.Then,it returns to the ground state(S₀) through a semiplanar conical intersection(CI)between??*₁ state and S₀.In comparison,when the lower energy??*₁state is initially populated,it decays through a different S₁/S₀ CI facilitated by C5=C6 torsion.Before reaching this CI,part of the population branches to a long-lived n _N?*state,which is not reached at higher energy excitation.This work clarify a more than 20-years's debate on the excited state dynamics of dCyd and 5mdCyd.Second,we investigated the excited state dynamics of 2'-deoxy-5-hydroxymethylcytidine(5hmdCyd),2'-deoxy-5-formylcytidine(5fdCyd) and 2'-deoxy-5-carboxylcytidine(5cadCyd).The results show that the modification on C5 position of cytidine significantly affects the excited state dynamics.For 5mdCyd and 5hmdCyd,C5 substitution affects the torsion of the double bond between C5 and C6,thereby hindering the internal conversion from??*₁ state to ground state,and prolonging the??*₁state lifetime.For 5cadCyd,the pyrimidine ring is more likely to reach the semi-planar structure,and the excited state can decay to the ground state via the corresponding CI.For 5fdCyd,the excited state intramolecular charge transfer occurs due to the presence of aldehyde group,and a n?*state with low energy is also present.As a result,several intersystem crossing channels are operative,and the triplet quantum yield is two orders of magnitude higher than that of dCyd.For 5cadCyd,pyrimidine ring is more likely to reach the semi-planar structure,and the excited state can decay to the ground state by the corresponding CI.Building on the complexity,we study the excited state dynamics of the nucleoside incorporated into DNA strands.First,the relaxation pathways of d(GC)₉·d(GC)₉with different secondary structures are studied.The results show that there are two excited state electron transfer pathways coupled with different vibronic modes in the Hoogsteen bases-pairing DNA.The direction of electron transfer can be regulated by isotope substitution.For Watson-Crick bases-pairing DNA,the proton-coupled electron transfer can also be regulated by isotope substitution.Finally,we studies the excited state dynamcis of d(G^5fC)₉·d(G^5fC)₉duplex where all canonical C residues are substituted by the epigenetic ^5fC that has a triplet yield of?70%.Because of the strong coupling between the interstrand charge transfer state and the??*₁ state,the excited state population can decay to charge transfer state on an ultrafast time scale,blocking the intrisic intersystem crossing in 5fdCyd.Meanwhile,we observed for the first time that charge transfer state can induce intersystem crossing that leads to a guanine triplet state.In summary,we investigated the ultrafast excited state dynamics of epigenetic nucleic acids and revealed the effect of epigenetic modification on the photophysical and photochemical properties of DNA.Our results lay the ground work to further understand the mechanism of DNA photo-damage induced by epigenetic modifications.