Theoretical Studies on the Structure and Various Physico-Chemical and Biological Properties of a Terphenyl Derivative with Immense Anti-Protozoan Activity

Theoretical calculations at the B3LYP/CC-pVDZ level were used to find the IR, Raman, VCD, and various molecular properties of a terphenyl derivative. Experimental and theoretical spectra agree within their respective limits. Partial density of states shows which parts of the molecules have the most important contribution to the FMO. Fluorine, sulfur, oxygen, and nitrogen atoms have practically insignificant contribution to the HOMO. Time dependent DFT calculations were used to study excitations, while natural transition orbitals were used to study the charge transfer in the strongest excitation. The experimentally observed FTIR modes are compared with calculated wavenumbers. Natural bond orbital analysis gives the idea about stability of molecules. MD simulations are used for calculating solubility parameters. Autoxidation and bond dissociation studies indicate stability of the compound. The docked ligands form secure complexes with the receptor methionyl-tRNA synthetase which indicates new anti-protozoan drugs.

本研究采用B3LYP/CC-pVDZ级别下的理论计算，获取了三联苯衍生物的红外（IR）、拉曼（Raman）、振动圆二色谱（Vibrational Circular Dichroism, VCD）信号及多种分子性质。实验光谱与理论光谱在各自的误差范围内吻合良好。局域态密度分析可明确分子的哪些结构片段对前沿分子轨道（Frontier Molecular Orbital, FMO）具有最显著贡献。氟、硫、氧及氮原子对最高占据分子轨道（Highest Occupied Molecular Orbital, HOMO）的贡献几乎可忽略不计。采用时间依赖密度泛函理论（Time-Dependent Density Functional Theory, TD-DFT）计算研究了分子的激发过程，并借助自然跃迁轨道（Natural Transition Orbital, NTO）分析了最强激发过程中的电荷转移行为。将实验观测到的傅里叶变换红外光谱（Fourier Transform Infrared Spectroscopy, FTIR）振动模式与计算得到的波数进行了对比。自然键轨道（Natural Bond Orbital, NBO）分析可阐明该分子的稳定性特征。采用分子动力学（Molecular Dynamics, MD）模拟计算了该化合物的溶解度参数。自动氧化与键解离实验研究证实了该化合物的稳定性。对接配体可与甲硫氨酰-tRNA合成酶受体形成稳定复合物，该结果为新型抗原生动物药物的开发提供了潜在思路。