Caffeine as base analogue of adenine or guanine: A theoretical study

• QM calculations are important in better understanding the DNA interactions.
• Caffeine interactions with DNA bases have evaluated.
• Caffeine has weak mutagenic effects.
• Comparison between CAF-T and CAF-C help in understanding the mutagenic effect.

The results of quantum mechanical calculations, including binding energies and results of the population analysis show that the GC and AT base pair complexes are more stable than the CAF-X ones (where CAF is caffeine and X = adenine (A), thymine (T), cytosine (C) and guanine (G)). Structural similarity between the CAF molecule and purine bases (G and A) provides the possibility of incorporation of the CAF molecule into the DNA macromolecule. By comparing the CAF-A and CAF-T complexes with the AT base pair, and the CAF-G and CAF-C complexes with the GC base pair, it was found that the formation of the CAF-T complex is more probable than the other complexes. Thus, the CAF molecule acts as an analogue base of A and can be incorporated into the DNA macromolecule and paired with T and C in normal and rare state, respectively. Indeed, the results show that formation of the CAF-C complex is less probable than the CAF-T one and an AT to GC conversion is rarely occurred in the next DNA replication, so the CAF molecule may be considered as a weak mutagenic compound. To examine solvent effect, the binding energies have been calculated in solvent for the most important structures of the CAF-G, CAF-T, CAF-A and CAF-C complexes. The results in solvent are in agreement with those in the gas phase.

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