Quantum Chemical Investigation of the Interaction of Thalidomide Monomeric, Dimeric, Trimeric, and Tetrameric Forms with Guanine DNA Nucleotide Basis in DMSO and Water Solution: A Thermodynamic and NMR Spectroscopy Analysis.

Thalidomide (TLD) was used worldwide as a sedative, but it was revealed to cause teratogenicity when taken during early pregnancy. It has been stated that the (R) enantiomer of TLD has therapeutic effects, while the (S) form is teratogenic. Clinical studies, however, demonstrated the therapeutic efficacy of thalidomide in several intractable diseases, so TLD and its derivatives have played an important role in the development and therapy of anticancer drugs. Therefore, it is important to know the molecular mechanism of action of the TLD, although this is still not clear. In what molecular interactions are concerned, it is known that drug molecules can interact with DNA in different ways, for example, by intercalation between base pairs. Furthermore, the ability of the TLD to interact with DNA has been confirmed experimentally. In this work, we report a theoretical investigation of the interaction of the R and S enantiomers of TLD, in its monomeric, dimeric, trimeric, and tetrameric forms, with guanine (GUA) DNA nucleotide basis in solution using density functional theory (DFT). Our initial objective was to evaluate the interaction of TLD-R/S with GUA through thermodynamic and spectroscopic study in dimethyl sulfoxide (DMSO) solvent and an aqueous solution. Comparison of the experimental