Noncovalent complexes of dimethyl sulfoxide with anticancer thioderivatives of purine nucleobases: insights into drug delivery mechanisms

Insight into molecular mechanisms of drug delivery enables development of new approaches for targeted drugs transportation. Facilitation of the transmembrane drug transfer is particularly significant for sparingly lipid-soluble medicines, as well as for certain anticancer drugs with high toxicity. In the present combined mass spectrometry and quantum chemical study we investigate intermolecular interactions between drug delivery facilitating agent dimethyl sulfoxide (DMSO) and selected anticancer thioderivatives of nucleobases. DMSO is a well-known enhancer of transmembrane and transdermal drugs penetration. Formation of stable noncovalent complexes of DMSO with 6-thiopurine and 2-thioadenine in the polar solvent methanol is revealed by the electrospray ionization mass spectrometry (ESI MS) probing. Structures and interaction energies are calculated using the MP2/aug-cc-pVDZ method for the complexes of DMSO with the anticancer agents observed in the ESI MS experiments. We also estimate the influence of the solvents on molecular interactions in the complexes. The calculation results confirm stability of the noncovalent complexes and provide information regarding their equilibrium structures. We believe that the study outcomes on the formation of stable noncovalent intermolecular complexes between the anticancer thioderivatives of nucleobases and the delivery facilitating molecules such as DMSO contribute to the elucidation of molecular mechanisms providing the drug delivery process.