Determination of Some Molecular Properties of a Series of Primaquine Molecules with Antimalarial Activity by the DFT (Density Functional Theory) Method

Abstract

This study evaluated selected molecular properties of five primaquine-derived compounds (PQ_1–PQ_5) with reported antimalarial activity using density functional theory (DFT). The investigation considered global chemical reactivity descriptors derived from frontier molecular orbitals, local reactivity indices, dipole moments, standard thermodynamic quantities of formation and lipophilicity. Molecular geometry optimisation and frequency calculations were performed in the gas phase at 298.15 K and 1 atm using the 6-311G(d,p) basis set. Local reactive sites were examined using Fukui functions and the dual descriptor, while lipophilicity was calculated using the Rekker fragmental method. The HOMO–LUMO energy gaps ranged from 3.4751 eV for PQ_5 to 3.9402 eV for PQ_1, identifying PQ_5 as the most chemically reactive and PQ_1 as the most chemically stable within the investigated series. Analysis of the local descriptors identified nitrogen atoms as preferred reactive sites for PQ_1, PQ_2 and PQ_4, whereas carbon and nitrogen sites differed for PQ_3 and PQ_5. All five molecules exhibited non-zero dipole moments (1.3706–2.7756 D) and positive calculated logP values (3.5030–5.1060), indicating polarity and lipophilicity. The calculated standard thermodynamic quantities of formation were negative for all compounds; PQ_2 exhibited the greatest thermodynamic stability by the criterion applied. These findings characterise differences within the selected series and provide a computational basis for subsequent experimental investigation.