College of Innovation and Entrepreneurship, Liaoning Institute of Science and Technology, Benxi, 117004, China.
College of Innovation and Entrepreneurship, Liaoning Institute of Science and Technology, Benxi, 117004, China.
Comput Biol Chem. 2020 Dec;89:107395. doi: 10.1016/j.compbiolchem.2020.107395. Epub 2020 Oct 1.
It has become obvious that fluorinated drugs have a significant role in medicinal applications. In this study, the fluorination of 3-nitrotyrosine as an anti-Parkinson and anti-Alzheimer drug was explored using density functional theory calculations. We have investigated the most important chemical properties of 3-nitrotyrosine that affect the pharmacological activity of the drug. We found that the intramolecular hydrogen bonding and intramolecular charge of the drug were influenced by fluorine substitution. Our results also reveal that the fluorination altered the stability, solubility, and molecular polarity of the 3-nitrotyrosine drug. The density of state analysis also determines sharp resonance states of fluorine atoms with the 3-nitrotyrosine drug states particularly in the highest molecular orbital reigns, suggesting hybridization of the fluorine states with the state of the drug. Moreover, our results show that the electronic spectra of fluorinated derivatives of 3-nitrotyrosine drug exhibit a red shift toward higher wavelengths (lower energies). Our calculations show that the free energy transfers of fluorinated derivatives of the 3-nitrotyrosine drug in water were negative that it meant that the designed molecules dissolving in aqueous phase occurred simultaneously. Consequently, the results of the present study show that the fluorination of 3-nitrotyrosine drug could be considered as a promising strategy to design useful drugs with better pharmacological properties.
很明显，含氟药物在医学应用中具有重要作用。在这项研究中，使用密度泛函理论计算探索了将 3-硝基酪氨酸氟化作为抗帕金森病和抗老年痴呆病药物的方法。我们研究了影响药物药理活性的 3-硝基酪氨酸的最重要化学性质。我们发现，药物的分子内氢键和分子内电荷受到氟取代的影响。我们的结果还表明，氟化改变了 3-硝基酪氨酸药物的稳定性、溶解度和分子极性。态密度分析还确定了氟原子与 3-硝基酪氨酸药物态之间的尖锐共振态，特别是在最高分子轨道范围内，表明氟态与药物态的杂化。此外，我们的结果表明，3-硝基酪氨酸药物的氟化衍生物的电子光谱显示出向更高波长（更低能量）的红移。我们的计算表明，3-硝基酪氨酸药物的氟化衍生物在水中的自由能转移为负值，这意味着设计的分子同时在水相溶解。因此，本研究的结果表明，3-硝基酪氨酸药物的氟化可以被认为是设计具有更好药理性质的有用药物的一种有前途的策略。
