Quantifying molecular interactions linking disordered and ordered phases to predict crystallisation

量化连接无序相和有序相的分子相互作用以预测结晶

• 批准号: EP/Z00005X/1
• 负责人: Katharina Edkins
• 金额: $ 275.22万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FZ00005X%2F1
• 关键词: Quantifying; molecular; interactions; linking; disordered

Even though crystallisation is one of the most used unit processes in the chemical and pharmaceutical industries, it is still impossible to predict the crystallisation outcome without conducting an experiment. The current practice of crystallisation screening costs industry between 50K and 120K Euros per compound in time and manpower. Streamlining this approach with the help of computational crystal structure prediction is currently curbed by computing power and the missing link between the predicted structures and the experimental conditions needed to produce them. Current attempts to investigate solution-state aggregation and its influence on the crystallisation outcome show varying success, are isolated, and do not allow for investigation to yield generalised insights.The aim of this project is to elucidate the molecular interactions in pre-crystallisation states and to link these with crystallisation outcomes. Using a combination of spectroscopic and total scattering techniques, I will extract strength and structure of homomeric interactions from the single component phase (melt or glass), solute-solvent interactions from solution, and the impact of binary solvent microheterogeneity and solvent-solvent interface on aggregation insolution. This approach will yield the fundamental understanding to enable the prediction of the crystallisation behaviour of compounds not investigated in this study. In addition, I will translate this fundamental knowledge into scale bars of interaction strength and easy-to-use rules comparable to Lipinski's 'Rule of Five' or the Biopharmaceutical Classification System allowing the application of the fundamental insights of this project in the everyday work of crystallisation scientists. This will lead to a step-change in how the community approaches crystallisation and enable a tailored and controlled approach to replace the current brute-force screening.

尽管结晶是化学和制药工业中最常用的单元工艺之一，但如果不进行实验，仍然不可能预测结晶结果。目前的结晶筛选实践在时间和人力上花费了每个化合物5万至12万欧元的工业成本。在计算晶体结构预测的帮助下简化这种方法目前受到计算能力和预测结构与产生它们所需的实验条件之间缺失的联系的限制。目前的尝试，调查溶液状态的聚集及其对结晶结果的影响表现出不同的成功，是孤立的，并不允许调查，以产生普遍的insights.The该项目的目的是阐明在预结晶状态的分子相互作用，并将这些与结晶结果。使用光谱和总散射技术相结合，我将提取的强度和结构的同聚物的相互作用从单组分相（熔体或玻璃），溶质-溶剂的相互作用从解决方案，和二元溶剂微观异质性和溶剂-溶剂界面上聚集insolution的影响。这种方法将产生的基本理解，使本研究中没有研究的化合物的结晶行为的预测。此外，我将把这些基本知识转化为相互作用强度的比例尺和易于使用的规则，与Lipinski的“五规则”或生物制药分类系统相媲美，从而将该项目的基本见解应用于结晶科学家的日常工作中。这将导致社区如何处理结晶的步骤发生变化，并使量身定制和受控的方法取代当前的暴力筛选。