Protonation of Cytosine-Rich Telomeric DNA Fragments by Carboxylated Carbon Nanotubes: Insights from Computational Studies.

In this work, we studied, using computational methods, the protonation reactions of telomeric DNA fragments being due to interaction with carboxylated carbon nanotubes. The applied computational methodology is divided into two stages. (i) Using classical molecular dynamics, we generated states in which carboxyl groups are brought to the vicinity of nitrogen atoms within the cytosine rings belonging to the DNA duplex. (ii) From these states, we selected two systems for systematic quantum chemical studies aimed at the analysis of proton-transfer reactions between the carboxyl groups and nitrogen atoms within the cytosine rings. Results of molecular dynamics calculations led to the conclusion that sidewall-functionalized carbon nanotubes deliver carboxyl groups slightly more effectively than the on-tip-functionalized ones. The latter can provide carboxyl groups in various arrangements and more diverse quality of approach of carboxyl groups to the cytosines; however, the differences between various arrangements of carboxyl groups are still not big. It was generally observed that narrow nanotubes can access the cytosine pocket easier than wider ones. Quantum chemical calculations led however to the conclusion that a direct proton transfer from the carboxyl group to the nitrogen atom within the cytosine ring is impossible under normal conditions. Precisely, we detected either very high activation barrier for the proton-transfer reaction or instability of the reaction product, i.e., its spontaneous decomposition toward reaction substrates.