目的：开发定量模型和相关工作流程，用于使用分子和晶体学建模从有机单晶的晶体结构预测其机械变形特性（塑性变形或解理断裂）。
方法：分子间合成子，氢键,使用经验力场对晶体形态和表面化学进行建模，并将数据集成到使用统计方法计算的晶格变形分析中。
结果：开发的方法包括三个主要组成部分。首先,基于晶格晶胞几何形状识别可能的变形方向；其次，通过计算面间分子间相互作用的强度和立体化学，确定可能的晶格平面变形，表面平面粗糙度和表面能；第三，通过评估分子间键合各向异性来识别潜在的解理断裂晶面。预测季戊四醇在<110>中通过强烈的面内氢键相互作用在{001}晶格平面上脆性断裂，而季戊四醇四硝酸酯预计会通过滑动系统{110}<001>的塑性变形而变形，这两个预测与已知的实验数据非常吻合。
结论：通过对晶格能学的定量评估，开发了预测分子晶体机械变形的晶体学框架和相关工作流程，晶体表面化学和晶体缺陷。强调了使用这种方法对药物材料的机械变形进行从头预测的潜力，因为它在设计通过直接压缩制造所需的配制药物产品过程中具有潜在的重要性。
OBJECTIVE: Development of a quantitative model and associated workflow for predicting the mechanical deformation properties (plastic deformation or cleavage fracture) of organic single crystals from their crystallographic structures using molecular and crystallographic modelling.
METHODS: Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields with the data integrated into the analysis of lattice deformation as computed using a statistical approach.
RESULTS: The approach developed comprises three main components. Firstly, the identification of the likely direction of deformation based on lattice unit cell geometry; secondly, the identification of likely lattice planes for deformation through the calculation of the strength and stereochemistry of interplanar intermolecular interactions, surface plane rugosity and surface energy; thirdly, identification of potential crystal planes for cleavage fracture by assessing intermolecular bonding anisotropy. Pentaerythritol is predicted to fracture by brittle cleavage on the {001} lattice planes by strong in-plane hydrogen-bond interactions in the <110>, whereas pentaerythritol tetranitrate is predicted to deform by plastic deformation through the slip system {110} < 001>, with both predictions being in excellent agreement with known experimental data.
CONCLUSIONS: A crystallographic framework and associated workflow for predicting the mechanical deformation of molecular crystals is developed through quantitative assessment of lattice energetics, crystal surface chemistry and crystal defects. The potential for the de novo prediction of the mechanical deformation of pharmaceutical materials using this approach is highlighted for its potential importance in the design of formulated drug products process as needed for manufacture by direct compression.
