Determination of Some Molecular Properties of a Series of Primaquine Molecules with Antimalarial Activity by the DFT (Density Functional Theory) Method
Fatogoma Diarrassouba *
Laboratoire de Thermodynamique et Physico-Chimie du Milieu (LTPCM), UFR-SFA, Université Nangui ABROGOUA, 02 BP 801 Abidjan 02, Côte d’Ivoire and Unité de Formation et de Recherche Sciences et Technologies (UFR-ST), Université Alassane Ouattara, 01 BP 18 Bouaké 01, Côte d’Ivoire.
Affoué Lucie Bede
Laboratoire de Constitution et de Réaction de la Matière (LCRM), UFR-SSMT, Université Félix Houphouët Boigny, 22 BP 582 Abidjan 22, République de Côte-d’Ivoire.
Ahissan Donatien Ehouman
Laboratoire de Thermodynamique et Physico-Chimie du Milieu (LTPCM), UFR-SFA, Université Nangui ABROGOUA, 02 BP 801 Abidjan 02, Côte d’Ivoire.
Mabintou Kalo
Unité de Formation et de Recherche Sciences et Technologies (UFR-ST), Université Alassane Ouattara, 01 BP 18 Bouaké 01, Côte d’Ivoire and Laboratoire des Procédés Industriels de Synthèse, de l’Environnement et des Energies Nouvelles, Institut National Polytechnique Félix Houphouët Boigny (LAPISEN), Yamoussoukro, Côte d’Ivoire.
Kafoumba Bamba
Laboratoire de Thermodynamique et Physico-Chimie du Milieu (LTPCM), UFR-SFA, Université Nangui ABROGOUA, 02 BP 801 Abidjan 02, Côte d’Ivoire.
Nahossé Ziao
Laboratoire de Thermodynamique et Physico-Chimie du Milieu (LTPCM), UFR-SFA, Université Nangui ABROGOUA, 02 BP 801 Abidjan 02, Côte d’Ivoire and Groupe Ivoirien de Recherches en Modélisation des Maladies (GIR2M), Université Nangui Abrogoua, Abidjan, Côte d’Ivoire.
*Author to whom correspondence should be addressed.
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.
Keywords: Primaquine, antimalarial activity, density functional theory, frontier molecular orbitals, HOMO–LUMO energy gap, global reactivity descriptors, local reactivity descriptors, Fukui functions, dipole moment, thermodynamic properties, lipophilicity