Incorporating molecular flexibility and conformational variability into crystal structure prediction

• Main Author: Gee, Thomas Simon
• Other Authors: Day, Graeme
• Published: University of Southampton 2017
• Subjects: 572
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.722957

The ability to predict the properties of a crystal structure before any empirical analysis or laboratory work has commenced offers the opportunity for vast reductions in research and development costs for new products. This research focuses on a novel methodology to incorporate molecular exibility into crystal structure prediction (CSP). Chapter 3: The quantification of the effect of incorporating molecular exibility and a revised Williams99 potential in the lattice energy minimisation finds that 5.5% and 6.3% more observed crystal structure matches, respectively, lie within 1kJ mol^-1 of the calculated global energy minimum structure. Chapter 4: A novel method is presented that simultaneously samples the molecularconformational space and the unit cell parameters when generating crystal structures where the former employs molecular principal displacements. This method was used for one test molecule that possesses 3 known polymorphs where only 1 is found when a standard CSP approach is used; this method now locates all 3 polymorphs. Chapter 5: Presents a scientically robust and computationally efficient method for finding a set of principal displacements and their corresponding contributions for converting one molecular conformation into another. Chapter 6: The molecular strain energy induced by crystal packing forces was calculated for 224 molecules. It was found that a maximum number of principal displacements up to a force constant value of 0:084 mDyneA^-1 were required to accurately reproduce the in-crystal conformation from its gas phase conformer for approximately 95% of cases. Chapters 7 & 8: Present two CSP case studies. The first was a sixth blind test molecule that failed to be predicted when using a rigid molecule search procedure coupled with a flexible molecule lattice energy minimisation and hence was used as motivation to implement the methodology presented in Chapter 4 on the second case study of a novel herbicide molecule.