Experimental and Theoretical Investigation of the Mechanism of Radiation-Induced Radical Formation in Hydrogen-Bonded Cocrystalas of 1-Methylcytosine and 5-Fluorouracil

摘要

The process of stabilizing radiation damage in the base pair of 1-methylcytosine (1-MeC);5-fluorouracil (5-FU) has been investigated.The formation of free radicals in purines and pyrimidines is influenced by the matrix in which they are irradiated.Of particular interest are the systems in which two different nucleic acid bases are complexed,providing situations that approximate the close proximity of bases in nucleic acid polymers.Detaied EPR/electron-nuclkear double resonance experiments show that only the N3 protonated cytosine anion and the N1 deprotonated uracil cation are observed in single crystals of 1-MeC:5-FU,X-irradiated,and observed at 10 K.Upon warming one observes a radical formed by net hydrogen addition to C6 on uracil,and an allyic racdical on the C4-C5-C6 reion of the uracil.No cytosine C5 or C6 H-addition radicals are observed.The implications that free radical damage is transferred from the eytosine moiety to the uracil moiety in 1-MeC:5FU is discussed.Single point calucations were performed on the optimized geometries at the B3LYP/6-311G(2df,p) level to obtain accurate energies and spin populations.To obtain electron affinities of the neutral parent molecules,the larger 6-31+G(2d,p) basis set was used.Rewsults show that the cytosine base will be the preferred site of electron addition,and thre uracil base will be the site of electtron loss.Additional studies were performed to investigate the influence of the hydrogen-bonded crystal matrix on the stabilities of the imitial radical ions.On the basis of these studies,a proton shuttle mechanism is proposed that provides an efficient transfer of charge away from the initial sites of electron addition or eelctron loss,leaving behind neutral radical sires that are less susceptible to recombination.