The Substituent Effects on Chemical Reactivity and Aromaticity Current of Ritalin Drug

In this study, the effects of four substitutions in two different positions of Methylphenidate (MPH, Ritalin) structure on chemical reactivity indices and aromaticity current of benzene ring were investigated at the density functional theory (DFT) level. The results were interpreted using natural bond orbital (NBO) analysis. The findings indicated that by increasing the participation of the studied substitutions in intramolecular interactions, their effect on the chemical reactivity indices and aromaticity current increased. Therefore, the substituents NO2 and Cl on the benzene ring, with the highest participation in intramolecular interactions, caused the highest increase in the resonance interactions of the benzene ring. As a result, they increased the values of the Nuclear Independent Chemical Shift (NICS) in the geometric center of the ring. Also, the above substitutions decreased the energy gap between HOMO (highest occupied molecular orbitals) orbitals and LUMO (lowest unoccupied molecular orbitals) and increased chemical reactivity indices. On the other hand, The NBO results represented that electron-withdrawing substituents at positions R7 and R9 reduced the accumulation of negative charge on adjacent atoms and the benzene ring.