Effect of the side chain on the properties from cidofovir to brincidofovir, an experimental antiviral drug against to Ebola virus disease

Abstract

In the present work, the structural, topological and vibrational properties of five members of the series C8H13N3O5POR (RH, (CH2)3OCH2CH3, (CH2)3O(CH2)7CH3, (CH2)3O(CH2)13CH3 and (CH2)3O(CH2)15CH3), where the first and the latter members are the two potential antiviral agents, cidofovir and brincidofovir, respectively, were studied by using density functional theory (DFT), natural bond orbital (NBO), atoms in molecules theory (AIM), frontier orbitals and molecular electrostatic potential (MEP) calculations and the hybrid B3LYP/6-31G∗ method. Here, the changes in the properties were followed modifying the side chain from cidofovir to brincidofovir. This study reveals clearly the differences in the properties when they change the longitude of the side chain. The high dipole moment value of brincidofovir together with the large side chain could explain the ability of brincidofovir to traverse biological membranes more rapidly than cidofovir while the low bond order that presents the POR bond in brincidofovir probably supports the quick removal of its side chain inside the cell. The frontier orbitals predicted a high reactivity and a higher electrophilicity index for brincidofovir, as compared with cidofovir. The complete assignment of the 90 vibration modes of cidofovir was proposed.