【作者】 刘星；

【导师】 谭凯；

【作者基本信息】 厦门大学 ， 物理化学， 2022， 硕士

【摘要】 人工自组装多面体体系由于其独特的性质在许多方面有着广阔的应用前景。特别是纯有机分子多面体,由于具有在一定条件下(pH、光照等)可逆组装或解组装,可通过药物负载而实现靶向给药,因而具有重要的实用价值。近年来实验科学家利用具有C3h对称性的聚三茚的醛基衍生物和乙二胺(三胺)作为非手性前驱体,通过动态可逆共价化学反应组装出纯有机三维手性多面体。探究该动态共价化学反应机理,进而考察药物负载的机理研究是物理化学、药物化学领域中非常重视和具有挑战性的前沿课题。目前对纯有机分子多面体及负载的研究正方兴未艾,实验研究仍有许多亟待解决的问题。本论文以纯有机分子多面体的物理化学性质为基础,利用密度泛函理论从原子分子层次上理解分子间非共价相互作用在分子组装、负载过程中的关键作用,并解释和预测实验现象。首先,我们利用考虑色散校正的新型密度泛函研究实验中合成的手性八面体,所得热力学量与实验值定性上一致。计算表明面旋转八面体异构体间稳定性存在差异,所有的热力学稳定产物在每个面上展现出一致的旋转方向性;比较不同泛函,考虑了色散校正的M06-2X泛函表现最好。其次,研究了手性八面体在负载药物后的几何构型和电子性质,分析其主要相互作用,计算表明手性八面体内的药物分子主要可以通过氢键或π-π堆积作用方式稳定结合。这从理论计算层面展现了手性八面体在药物输送和手性拆分方面应用的潜力,为预测、设计和发展高效可控面旋转手性分子多面体载体提供理论指导。最后,利用席夫碱反应,我们在理论上预测了一类新的纯有机四面体的结构和电子性质,通过对P4分子负载的研究,揭示了π-π堆积作用、孤对-π等弱相互作用的存在,通过和实验上合成的非面旋转四面体负载的比较,我们阐明了负载作用的机制,开启了理论上更深层次理解分子间非共价相互作用在药物负载调控中的作用。更多还原

【Abstract】 The artificial self-assembly polyhedron system has broad application prospects in many aspects due to its unique properties.In particular,pure organic molecular polyhedrons have important practical value because they can be reversibly assembled or disassembled under certain conditions(PH,light,etc.)and can be targeted by drug delivery.In recent years,experimental scientists have used aldehyde derivatives with C3h symmetry polytriterpenoids and ethylenediamine(triamine)as achiral precursors to assemble pure organic three-dimensional chiral polyhedrons through dynamic reversible covalent chemical reactions.Exploring the mechanism of the dynamic covalent chemical reaction and then examining the mechanism of drug delivery is an important and challenging topic in the field of physical chemistry and medicinal chemistry.At present,the research on polyhedral and loading of pure organic molecules is in the ascendant.There are still many problems to be solved in the experimental research.In this dissertation,based on the physicochemical properties of pure organic molecular polyhedrons,the key role of non-covalent interactions between molecules in the process of molecular assembly and loading is understood from the atomic molecular level using density functional theory,and the experimental phenomena are explained and predicted.First,we used a novel density functional study of dispersion correction to study the chiral octahedron synthesized in the experiment.The thermodynamic quantities obtained were qualitatively consistent with experimental values.The calculations show that there is a difference in the stability between the octahedral isomers of the surface rotation,and all the thermodynamically stable products exhibit a uniform rotational directionality on each surface;comparing the different functionalities,the dispersioncorrected M06-2X functional expression is considered to be the most representative.Secondly,the geometry and electronic properties of the chiral octahedron after loading the drug were studied,and the main interactions were analyzed.The calculations show that the drug molecules in the chiral octahedron can be mainly stabilized by hydrogen bonding or π-π stacking.This shows the potential of the application of chiral octahedrons in drug delivery and chiral separation from theoretical calculations,and provides theoretical guidance for the prediction,design,and development of highly efficient controllable plane-rotating chiral polyhedral carriers.Finally,using the Schiff s base reaction,we theoretically predict the structure and electronic properties of a new class of pure organic tetrahedra.By studying the loading of P4 molecules,the π-π stacking effect and the lone pair-π are revealed.The existence of such weak interactions,through comparison with experimentally synthesized nonplane rotating tetrahedral loads,elucidated the mechanism of the loading action and opened theoretically a deeper understanding of the intermolecular non-covalent interactions in the regulation of drug delivery.更多还原