Improving Crystal Structure Prediction via Tailored Force Fields

点击翻译按钮获取中文摘要

There has been tremendous progress in recent years in the development of practical approaches to crystal structure prediction (CSP) for polymorphic molecules and co-crystal systems. It is now possible to predict the crystal energy landscape of molecules of practical agrochemical or pharmaceutical interest, with multiple flexible torsions and bond angles. CSP studies can now support decision making and risk management, either by helping to design experiments aimed at crystallising a specific structure or by offering re-assurance that all likely polymorphs have already been identified. Given a sufficiently accurate model, such studies can also form the basis for the prediction of numerous crystal and solution properties. Current state-of-the-art techniques, such as those incorporated in the CrystalPredictor and CrystalOptimizer codes developed by the groups of Claire Adjiman and Costas Pantelides, generally assume that the only available information is the molecular structure. Although this assumption significantly widens the applicability of the approach, it is often unnecessarily restrictive. In particular, one or more crystal structures for the compound of interest may already be already known or may be identified during the course of active ingredient development. To fully realise the potential of CSP techniques within an industrial context, it is important to make use of all such available information. The aim of this project is to develop a CSP methodology that can take advantage of prior knowledge in order to achieve greater accuracy and reliability. The use of such information to accelerate the search for polymorphs will also be investigated. The proposed project will build on recent work within the Molecular Systems Engineering group at Imperial College that has highlighted the importance of the empirical repulsion/dispersion terms used in many of the models at the heart of CSP. This has led to techniques and codes for the derivation of improved parameter values using available experimental structures. Overall, this has been found to lead to much more accurate lattice energy calculations. However, this work has been focused on rigid molecules, which are simpler than the more flexible molecules typical of the agrochemicals industry.The primary objective of the proposed project will be develop a formal framework for determining force fields that are tailored to specific compounds of interest. Our proposed approach will combine ab initio CSP techniques with prior solid state information that is available for these or closely-related compounds. The effectiveness of the new methodology will be assessed via testing on several compounds of industrial relevance.