Patel Subham G, Vala Ruturajsinh M, Patel Paras J, Upadhyay Dipti B, Ramkumar V, Gardas Ramesh L, Patel Hitendra M
Department of Chemistry, Sardar Patel University Vallabh Vidyanagar 388120 Gujarat India
Department of Chemistry, Indian Institute of Technology, Madras India.
RSC Adv. 2022 Jun 29;12(29):18806-18820. doi: 10.1039/d2ra02694e. eCollection 2022 Jun 22.
Herein, acetic acid mediated multicomponent synthesis of novel 2,4-dimethoxy-tetrahydropyrimido[4,5-]quinolin-6(7)-one (2,4-dimethoxy-THPQs) was reported. Single-crystal XRD analysis of four newly developed crystals of 2,4-dimethoxy-THPQs and their DFT study were also reported. The structure of all molecules was optimized using DFT B3LYP/6-31G(d) level and compared with the corresponding single-crystal XRD data. As a result, the theoretical and experimental geometrical parameters (bond lengths and bond angles) were found to be in good agreement. Frontier molecular orbital (FMO) and molecule electrostatic potential (MEP) analyses were used to investigate the physicochemical properties and relative reactivity of 2,4-dimethoxy-THPQs. The formation of strong C-H⋯O and N-H⋯O interaction was investigated by Hirshfeld analysis. Furthermore, electronic charge density concentration in 2,4-dimethoxy-THPQs was analysed by the Mulliken atomic charges which helps to predict the ability of 2,4-dimethoxy-THPQs to bind in the receptor. The molecular docking of the crystal structure of 2,4-dimethoxy-THPQs in the main protease (M) of SARS-CoV-2 suggested that all four 2,4-dimethoxy-THPQs efficiently docked in M. Furthermore, 2,4-dimethoxy-THPQs with a 3-chloro substitution in the phenyl ring have the highest binding affinity because of the additional formation of halogen bonds and highest dipole moment.
本文报道了乙酸介导的新型2,4-二甲氧基-四氢嘧啶并[4,5-]喹啉-6(7)-酮（2,4-二甲氧基-THPQs）的多组分合成。还报道了四种新开发的2,4-二甲氧基-THPQs晶体的单晶XRD分析及其DFT研究。所有分子的结构均使用DFT B3LYP/6-31G(d)水平进行优化，并与相应的单晶XRD数据进行比较。结果发现，理论和实验几何参数（键长和键角）吻合良好。利用前沿分子轨道（FMO）和分子静电势（MEP）分析来研究2,4-二甲氧基-THPQs的物理化学性质和相对反应活性。通过Hirshfeld分析研究了强C-H⋯O和N-H⋯O相互作用的形成。此外，通过Mulliken原子电荷分析了2,4-二甲氧基-THPQs中的电子电荷密度浓度，这有助于预测2,4-二甲氧基-THPQs与受体结合的能力。2,4-二甲氧基-THPQs晶体结构在SARS-CoV-2主要蛋白酶（M）中的分子对接表明，所有四种2,4-二甲氧基-THPQs都能有效地对接在M中。此外，苯环上有3-氯取代的2,4-二甲氧基-THPQs由于额外形成了氢键和具有最高的偶极矩，具有最高的结合亲和力。
