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Purpose: To test the integrity of the thymine molecule that experiences an increasing number of charges due to the loss of Auger electrons emitted by the decay of incorporated ¹²⁵I. Besides the radiation action of these electrons, Coulomb explosion is suspected to be an additional mechanism responsible for the strong radiotoxic effect of decaying DNA‐incorporated ¹²⁵I. The two‐step decay process initiates a first Auger cascade within 10⁻¹⁶ to 10⁻¹⁴ s resulting in the release of about 7 electrons on average and a corresponding large positive charge on the ¹²⁵Te daughter atom. Being part of iododeoxyuridine (¹²⁵IUdR), the analogue of the DNA base thymine, the base is suddenly confronted with this charge. Experimentally, the situation was investigated with small molecules (CH₃¹²⁵I and C₂H₅¹²⁵I) resulting in ion fragmentation in agreement with a Coulomb explosion model (Carlson and White, 1963, 1966).

Materials and methods: Semi‐empirical quantum mechanical calculations on the Parametric Method 3 (PM3) level (Stewart, 1989a, 1989b) were performed and geometry optimisation was applied for the identification of stable molecule conformations. Subsequently, semi‐empirical molecular dynamics simulations allowed changes in the conformations to be studied as a function of time.

Results: First results show that there is no stable molecular configuration with a total charge of ≥+5e. PM3 calculations will not converge for such a charge located at the ¹²⁵I/¹²⁵Te position. This finding is supported by total energy considerations, which begin to favour a system of isolated atoms versus molecular bound atoms when the molecular charge is greater than +4e. The distribution of the partial charges indicates that most of the charge will remain on the tellurium atom with slight increases of charge at the other molecular partners within ¹²⁵IUdR. Moreover, the molecular dynamics simulations reveal a breaking of chemical bonds between those atoms with the strongest charge increase.

Conclusions: Coulomb explosion must be taken into account as a possible damaging mechanism following the decay of DNA‐incorporated Auger electron emitters. Lobachevsky and Martin (2000) have identified the same mechanism to be responsible for part of strand breakage in oligo‐deoxynucleotides. To elucidate a possible link between both damage patterns the molecular mechanics simulations have to be extended to larger parts of the DNA molecule.