Study On The Repair Reaction Mechanisms Of Deoxyguanosine And Deoxycytidine Radicals By Cysteine

The repair reaction mechanisms of dehydrogenation radicals of deoxyguanosine and deoxycytidine by cysteine(CysSH)have been investigated at B3LYP/ 6-311++G(d,p)level.The geometric structures of all reactants,intermediates,transition states and products were optimized and the potential energy surfaces were obtained.The results show that all the repair reactions are thermodynamically spontaneous exothermic.The results are as follow as:(1)The repair activation energies of G(-H1)·,G(-H2a)· and G(-H2b)· by CysSH are 6.85,4.44 and 8.10 kcal/mol in the gas phase,and those in the aqueous medium are 6.59,4.69 and 9.85 kcal/mol,respectively.Therefore,the repaired of G(-H2a)· is the most likely to occurs,followed by G(-H1)· and G(-H2b)·.While during the repair of dG(-H)·,the repair activation energies of dG(-H1)·,dG(-H2a)· and dG(-H2b)· by CysSH are 4.32,4.39 and 6.30 kcal/mol,respectively,the repairs of dG(-H1)· and dG(-H2a)· are more likely to occurs.In the aqueous medium,however,the activation energies are 6.29,4.67 and 5.43 kcal/mol respectively,thus,dG(-H2a)· is easiest one to be repaired.Solvent effect makes repair of dG(-H1)· more difficult.It makes repair the dehydrogenation radical of guanine easy in the two phases in the presence of deoxyribose,and makes the repair ctivation energy of dG(-H2b)· reduce by 4.42 kcal/mol in the aqueous medium.(2)The repair activation energies of C(-H4a)·,C(-H4b)· and C(-H6)· by CysSH are 2.34,2.23 and 3.59 kcal/mol in the gas phase,respectively,and those in the aqueous medium are 1.70,1.88 and 0.86 kcal/mol,with decreased of 0.64,0.35 and 2.73 kcal/mol,respectively.The repairs of C(-H)· in both phases are easily and repair of C(-H6)· is the easiest in the aqueous medium.The repair activation energies of dC(-H4a)·,dC(-H4b)· and dC(-H6)· by CysSH are 2.04,2.36 and 3.52 kcal/mol in the gas phase,respectively,and those are 1.67,2.25 and 3.14 kcal/mol in the aqueous medium,respectively.dC(-H4a)· is the most easily to be repaired and dC(-H6)· is the hardest to be reapired.The presence of deoxyribose would changed the the order of repair cytosine dehydrogenation radical.For example,in the aqueous medium,the repair of dC(-H6)· is much more difficult than that of C(-H6)·.(3)It is found that both normal and abnormal repairs would take place at C1?,C3? and C4? sites.The repair activation energies of dG(Cn?)· in the gas phase lie between 0.70 and 8.97 kcal/mol,and the order of the repair activation energy is EdG(C3?)·< EdG(C4?)·<dG(C5b?)·<d G(C1?)·<EdG(C1?)·<dG(C3?)·<dG(C5a?)·<dG(C2a?)·<dG(C2b?)· <dG(C4?)·(abnormal repair donetd as “E”).Thus,the abnormal repair activation energies at C3?and C4? sites are lower than those of the normal repairs,and abnormal repairs are more likely to take place at C3?and C4? sites.While the repair activation energies of dC(Cn?)· lie between 1.70 and 6.53 kcal/mol,and the order of the repair activation energy is dC(C5b?)·<dC(C5a?)·<dC(C3?)·<dC(C1?)·<dC(C4?)·<EdC(C1?)·<dC(C2b?)·<EdC(C4)· <dC(C2a?)·<EdC(C3?)·.Compared with the abnormal repair activation energies,the normal repair activation energies at C1?,C3?and C4? sites are lower,which means in the gas phase,normal repair is more likely to take place in the reaction of CysSH and dC(-H?)·.In the aqueous medium,the repair activation energies of dG(Cn?)· lie between-0.50 and 6.73 kcal/mol,and the order of the repair activation energy is dG(C5a?)·<EdG(C3?)·< EdG(C4?)·<EdG(C1?)·<dG(C1?)·<dG(C3?)·<dG(C5b?)·<dG(C4?)·<dG(C2a?)·<dG(C2b?)·,which shows the abnormal repair activation energies at C1?,C3?and C4? sites are lower than the normal ones.The repair activation energies of dG(Cn?)· lie between-1.77 and 4.57 kcal/mol,and the order of the repair activation energy is EdC(C3?)·<dC(C5a?)·<dC(C5b?)· <dC(C3?)·<EdC(C1?)·<dC(C2b?)·<dC(C1?)·<dC(C4?)·<dC(C2a?)·<EdC(C4?)·.It shows that the abnormal repair activation energies at C1? and C3? sites are lower than the normal ones,which indicates that the abnormal repair is much easier to take place at C1? and C3? sites.The repair of dG(Cn?)· in the gas phase,the ratios ? of ?: ? at the C1',C3' and C4'sites are 11.89,0.002 and 0.03,respectively.Abnormal repair is more likely to take place at C3' and C4' sites.The repair of dC(Cn?)·,the ratios ? of ?: ? at the C1',C3' and C4'sites are 1.69,18.42 and 2.66,respectively.In the aqueous medium,it is found that the repair of dG(Cn?)·,the ratios ? of ?: ? at the C1',C3' and C4' sites are 1.16,0.02 and 2.8 respectively,while repair of dC(Cn?)·,the ratios ? of ?: ? at the C1',C3' and C4' sites are 0.04,0.08 and 1.22,respectovely.This shows both the difference of base and the solvation effect can cause the change of proportion of the ?: ?.The repair activation energies at the C2? sites are larger than those at the C5? sites both in the gas phase and aqueous medium,which means it's more easier to repair the C5?· than that of C2?·.In this paper,the repair of deoxyguanosine and deoxycytidine radicals by cysteine is fully studied using DFT theory.Cysteine can effectively repair the base and deoxyribose dehydrogen radicals in DNA.In repairing the of deoxyribose radicals by cysteine,DNA mutation may be caused duo to the abnormal repair at C1',C3' and C4' sites.Besides,the solvent effect can also affect the repair process.We hope that this study has some guiding significance for non-enzymatic repair,i.e.chemical repair.