Here, we analyze the stereodynamic properties of bullvalenes using principal moments of inertia and exit vector plots to draw comparisons with commonly used ring systems in medicinal chemistry. To aid analyses, we first classify (i) the four elementary rearrangement steps available to substituted bullvalenes, which (ii) can be described by applying positional descriptors (α, β, γ, and δ) to the substituents. We also (iii) derive an intuitive equation to calculate the number of isomers for a given bullvalene system. Using DFT-modelled structures for di-, tri-, and tetrasubstituted bullvalenes, generated using a newly developed computational tool (bullviso), we show that their 3D shapes and the exit vectors available from the bullvalene scaffold make them comparable to other bioisosteres currently used to replace planar aromatic ring systems in drug discovery. Unlike conventional ring systems, the shapeshifting valence isomerism of bullvalenes gives rise to numerous shapes and substituent relationships attainable as a concentration-independent dynamic covalent library from a single compound. We visualize this property by applying population weightings to the principal moments of inertia and exit vector analyses to reflect the relative thermodynamic stabilities of the available isomers.

中文翻译：

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Bullvalene 立体动力学指南


在这里，我们使用主惯性矩和出口矢量图分析了牛瓦烯的立体动力学性质，以与药物化学中常用的环系统进行比较。为了帮助分析，我们首先对（i）可用于取代的布尔瓦烯的四个基本重排步骤进行分类，（ii）可以通过对取代基应用位置描述符（α、β、γ和δ）来描述。我们还 (iii) 推导出一个直观的方程来计算给定的 Bullvalene 系统的异构体数量。使用新开发的计算工具（bullviso）生成的二、三和四取代的 Bullvalene 的 DFT 模型结构，我们表明它们的 3D 形状和 Bullvalene 支架提供的退出向量使它们与目前使用的其他生物电子等排体具有可比性在药物发现中取代平面芳香环系统。与传统的环系统不同，牛瓦烯的变形价异构现象产生了多种形状和取代基关系，可作为单一化合物的浓度无关的动态共价库获得。我们通过将总体权重应用于主惯性矩和出口矢量分析来可视化此属性，以反映可用异构体的相对热力学稳定性。