Solid State NMR and Molecular Dynamics studies of solid crystal systems

Abstract

Solid state systems can often exhibit dynamics on the molecular level, changing conformations, rotating or moving across a crystal structure. In this work, a combination of Nuclear Magnetic Resonance (NMR), Molecular Dynamics (MD) and Markov models are utilised to describe and explain the dynamics seen on solid crystals and pharmaceutical solvates. NMR is used first to gain an idea of the dynamics, with relaxation rates used to measure activation energies and motional models suggested to fit the data. MD simulations are performed to directly simulate the motion, with the extraction of copies of each molecule from each simulation allowing motion on timescales greater than the simulation time to be observed. The simulations are analysed utilising Markov modelling, assigning conformations to states, extracting state samples to determine the metastable conformations and calculating transition times between these states.

Several of the lower diamondoids are analysed, providing descriptions of the motion and agreeing with previously suggested models of the dynamics. These also show some of the technical considerations that need to be taken into account when analysing systems using relatively short simulations. However, good agreement with experiment can still be achieved with these methods with careful planning. Two pharmaceutical solvates are also investigated, allowing a picture of the rapid solvent motion to be obtained. These pictures give some interesting avenues for further investigation, as well as showing this method can be applied to different solid systems.