Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Cátedra de Química General, Instituto de Química Inorgánica, Facultad de Bioquímica. Química Y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, (4000) San Miguel de Tucuman, Tucumán, Argentina.
J Mol Model. 2021 Nov 23;27(12):357. doi: 10.1007/s00894-021-04962-3.
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 NH group and NH group reveals lower solvation energy compared with other antiviral agents with an NH 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 NH groups by solvent molecules, the calculations in solution produce variations not only in the IR wavenumbers bands, but also in their intensities.
通过 B3LYP/6-311 + + G**计算，对合成的环己烯羧酸酯抗病毒奥司他韦（O）进行了理论研究，以估计其在气相和水相介质中的反应性和行为。在上述两种介质中得到的最稳定结构与奥司他韦磷酸盐的实验报道结构一致。（O）在水相中的溶剂化能值介于抗病毒碘苷和利巴韦林之间。此外，（O）中含有一个 NH 基团和一个 NH 基团，与其他含有 NH 基团的抗病毒药物（如利巴韦林、西多福韦和布西福韦）相比，其溶剂化能较低。受体和供体基团中 N 和 O 原子的原子电荷在两种介质中表现出不同的行为，而自然键轨道（NBO）研究表明（O）在水溶液中具有更高的稳定性。这一结果与在水中表现出的较低反应性一致。前沿轨道研究表明，（O）在气相中的带隙值与用于治疗埃博拉病的抗病毒药物西多福韦非常相似，而在两种介质中，氯喹的反应性都比（O）强。这项研究将允许通过振动光谱来识别（O），因为已经使用从比例力学力场方法（SQMFF）计算得出的谐用力场计算分配了预期的 144 个振动模式。还首次报道了（O）在所述介质中的比例力常数。由于溶剂分子对 C = O 和 NH 基团的水合作用，计算结果不仅在红外波数带中产生变化，而且在其强度上也产生变化。
