Molecular dynamics of a proguanil derivative

Abstract

Proguanil is a prophylactic antimalarial drug that is very effective against sporozoites and works by stopping the malaria parasites from reproducing inside the red blood cells. In this work, the molecular dynamics of a derivative of Proguanil is studied. A Hydrogen atom at position 3 on the benzene ring of the molecule of Proguanil is substituted by chlorine atom to give the desired derivative. The molecular geometries of Proguanil derivative are studied using ab-initio Quantum chemical calculations at the Restricted Hatree-Fock (RHF) level of theory using the basis sets 6- 31G(d,p) and 6-31++G. Also, Density Functional Theory (DFT) calculations at B3LYP with 6- 31G(d,p) and 6-31++G basis sets were carried out for inclusion of electron correlation. The dipole moments, thermal energies, quadrupole moment, polarizibility and optimized bond length computations for the molecule are obtained. The dipole moment of the Proguanil’s derivative at both levels of theory is less than that obtained for original malaria drug Proguanil. This indicates that the derivative Proguanil responds significantly more than Proguanil to an applied electric field. The Infra Red (IR) and Raman vibrational frequencies are vividly examined and the most intense IR and Raman frequencies are identified. The computation was performed using Gaussian 03W software.

Keywords: Proguanil, Density Functional Theory, Restricted Hartree Fock, Gaussian