Effect of the Protic vs. Non-Protic Molecular Environment on the to Conformation Change of Phototrexate Drug.

The therapeutical applicability of the anticancer drug phototrexate, a photoswitchable derivative of the antimetabolite dihydrofolate reductase inhibitor methotrexate, highly depends on the stability of its bioactive isomer. Considering that only the configuration of phototrexate is bioactive, in this work, the effect of the molecular environment on the stability of the isomer of this drug has been investigated. UV-vis absorption and fluorescence-based solvent relaxation methods have been used. Protic methanol and non-protic dimethylsulfoxide were used as medium-ranged permittivity solvents. The results showed a decreased rate of conversion and enhanced stabilities of the isomer in methanol. Temperature-dependent measurements of the isomerization rate reflect the increased activation energy in methanol.