Abstract

Valacyclovir HCl hydrate, acyclovir and ganciclovir are three commonly used anti viral drugs which are guanidine derivatives with ether side chain and all of them act by interfering with the viral DNA production. This manuscript tries to examine the structure and properties of these three purine based compounds using electronic structure methods and molecular mechanics. Density functional theory was used to optimize the ground state geometry of the molecules from frontier molecular orbitals are analyzed using B3LYP functional. They give wealth of information about the electronic properties and descriptors, which will enable to predict the bioactivity of the molecules. As the electrons interact with electromagnetic radiations, electronic excitations between different energy levels are analyzed in detail using TD-DFT with CAM-B3LYP orbital. Calculations shows that they are with excellent light-harvesting efficiency hence be used as photo sensitizers. Molecular docking studies predict the biological activity of the molecules against ADP-thymidine kinase, hence inhibits its action, subsequently affecting the viral DNA production. It is interesting to see that on adsorption with a graphene quantum dot surface, all adsorbed complex show enhancement in the Raman activity giving Surface Enhanced Raman Spectra (SERS) when studied using dispersion force corrected ω-B97XD functional. This can be used for the detection of these drugs in a pharmacological or biological sample. Interestingly the graphene drug molecular assembly shows enhanced biological activity when compared to individual drug molecules.

摘要

盐酸伐昔洛韦、阿昔洛韦和更昔洛韦是三种常用的抗病毒药物，它们都是具有醚侧链的胍衍生物，它们都通过干扰病毒DNA的产生而起作用。本手稿试图使用电子结构方法和分子力学检查这三种嘌呤基化合物的结构和性质。密度泛函理论用于优化分子的基态几何形状，使用 B3LYP 泛函分析来自前沿分子轨道的分子。它们提供了有关电子特性和描述符的大量信息，这将有助于预测分子的生物活性。当电子与电磁辐射相互作用时，使用具有 CAM-B3LYP 轨道的 TD-DFT 详细分析不同能级之间的电子激发。计算表明它们具有优异的光捕获效率，因此可用作光敏剂。分子对接研究预测了分子对 ADP-胸苷激酶的生物活性，因此抑制了其作用，随后影响了病毒 DNA 的产生。有趣的是，在使用石墨烯量子点表面吸附时，当使用色散力校正的 ω-B97XD 泛函进行研究时，所有吸附的复合物都显示出拉曼活性的增强，从而提供了表面增强拉曼光谱 (SERS)。这可用于检测药理学或生物样品中的这些药物。有趣的是，与单个药物分子相比，石墨烯药物分子组装体显示出增强的生物活性。