Abstract
Different crystal structures can possess different properties and therefore the control of
polymorphism in molecular crystals is a goal in multiple industries, e.g. the pharmaceutical
industry. Part I of this thesis is a computational study at the molecular scale of a particular
solid-solid polymorphic transition with the help of different modelling techniques. The
studied crystal is the amino acid DL-norleucine and the b $ a polymorphic transition is
specifically the topic of research. The cooperative behaviour of molecules during this transition
is discussed both from a computational and an experimental perspective. Also the
relative energy barriers of the different shifts involved in the transition have been determined.
Part II of the thesis is focussed around a new method to describe intermolecular interaction
energies in molecular crystals and can therefore also be used to compare different
polymorphic forms with each other. This method is named q-GRID and it uses the electron
density as obtained within the crystal as an input to calculate a crystal graph that can be
used to model nucleation rates, morphologies or as a direct estimation of the lattice energy.
q-GRID can be considered as a natural extension of the PIXEL method, that has been developed
by prof. Gavezzotti. The last chapter of this thesis describes the participation of
the Radboud University (RU) Nijmegen to the Sixth Blind Test on Organic Crystal Structure
Prediction Methods that has been organized by the Cambridge Crystallographic Data
Centre (CCDC). Within this participation q-GRID has been used.
