It has been over 2000 years since the first mechanochemical reaction was recorded, and while there has been great advancement in the field, there remains a general lack of understanding of the processes at the molecular level. This thesis aims to begin to develop an understanding of these processes, by studying the mechanochemical coÂcrystallisation of aspirin and meloxicam, from experimental and modelling approaches. Experimentally, it is shown that contrary to the original mechanosynthesis, in which the liquid assistant chloroform was required, that the desired co-crystal can be formed under neat grinding conditions, with a grinding frequency of 25 Hz. It is then demonstrated that the addition of 0.1 mol. equiv. of chloroform to the system allows the reaction to be performed with a grinding frequency of just 10 Hz. From the perspective of computer simulation, aspirin, meloxicam and their 1:1 co-crystal are successfully simulated using both density functional theory and force field methods. This is evidenced by the accurate calculation of various physical properties of the systems, including the formation energies, assorted surface energies and the bulk moduli of aspirin and meloxicam along with the cohesive energy of the co-crystal. Then, two studies are performed using force field molecular dynamics, the first of which shows that the phenomenon of localised heating is minimal in the mechanochemical co-crystallistaion reaction. The second, shows that the relative orientation of molecules changes the efficiency of the transfer of material between the two species and that partial solvation of the system, with chloroform, does not affect the transfer efficiency. It is suggested that chloroform’s role in the reaction is performed at a later stage, i.e. after the materials have become thoroughly mixed. This work will help us to understand the processes that occur at the molecular level during a mechanochemical reaction.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:726338 |
| Date | January 2017 |
| Creators | Ferguson, Michael |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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