Behaviours of antiviral Oseltamivir in different media: DFT and SQMFF calculations

J Mol Model. 2021 Nov 23;27(12):357. doi: 10.1007/s00894-021-04962-3.

Abstract

The synthetic cyclohexenecarboxylate ester antiviral Oseltamivir (O) have been theoretically studied by B3LYP/6-311 + + G** calculations to estimate its reactivity and behaviour in gas and aqueous media. The most stable structure obtained in above media is consistent with that reported experimental for Oseltamivir phosphate. The solvation energy value of (O) in aqueous media is between the predicted for antiviral Idoxuridine and Ribavirin. Besides, (O) containing a NH2 group and NH group reveals lower solvation energy compared with other antiviral agents with an NH2 group, such as Ribavirin, Cidofovir, and Brincidofovir. Atomic charges on N and O atoms in acceptors and donor groups reveal different behaviours in both media, while the natural bond orbital (NBO) studies show a raised stability of (O) in aqueous solution. This latter resulted is in concordance with the lower reactivity evidenced in water. Frontier orbital studies have revealed that (O) in gas phase has a very similar gap value to antiviral Cidofovir used against the ebola disease, while Chloroquine in the two media are more reactive than (O). This study will allow to identify (O) by using vibrational spectroscopy because the 144 vibration modes expected have been assigned using the harmonic force fields calculated from the scaled mechanical force field methodology (SQMFF). Scaled force constants for (O) in the mentioned media are also reported for first time. Due to hydration of the C = O and NH2 groups by solvent molecules, the calculations in solution produce variations not only in the IR wavenumbers bands, but also in their intensities.

Keywords: DFT calculations; Force fields; Oseltamivir; Structural properties; Vibrational study.