No abstract

The current study mainly focuses on the investigation of the antioxidant property and the dynamic behaviour of four antifolate molecules and comparision with folic acid. DFT (wB97X/6‐31+G(d)) level of theory was employed to calculate the N‐H bond dissociation energy (BDE) of the heterocyclic amino group and vertical ionization potential (IPv) of the molecules in water. The results reveal that studied antifolate molecules are very similar to folate with respect to the antioxidant property. Spin density plots and second‐order perturbation energies (E2) were calculated to show the stability of the hydrogen abstracted radicals and radical cations resulting from the folate and antifolate molecules. In addition, MD simulations were carried out to investigate conformational stability of molecules. Various properties like hydrogen bond, RMSD, SASA, cluster structure analysis were explored to study the conformational behaviour of the molecules. The results obtained from MD simulations are again very similar for folate and antifolates under investigation. The results obtained from the current study would help to understand the interaction of the antifolate molecules with folic acid receptors and also to design new molecules with better activity as drugs.