Molecular organic crystals are widely used for applications in the pharmaceutical and agrochemical sectors. These crystals are often formed as part of a mixture of molecular components, forming co-crystals and solid solutions which impacts properties such as solubility and dissolution rates. Solid form molecular mixtures may give rise to chemical as well as structural heterogeneity across length scales. Understanding the nanoscale structure of these materials is therefore important to understand the resulting properties, physical or mechanical, in the development of new products for application as pharmaceuticals and agrochemicals. Many techniques traditionally used to characterise the structure of these systems are limited when it comes to the analysis of heterogeneity at the nanoscale. Scanning transmission electron microscopy (STEM) and specifically scanning electron diffraction (SED) is an emerging technique that offers high spatially resolved structural information at low electron doses, whilst associated spectroscopic methods can offer information on chemical heterogeneity. In this thesis SED and spectroscopic STEM-based techniques are used to study two organic solid solution systems; a replica leaf wax system of an n-alkane (n-hentriacontane, C31H64), and an n-alkanol (1-triacontanol, C30H61OH), and a barbituric acid (BA) and thiobarbituric acid (TBA) solid solution system for pharmaceutical applications.
This work first reveals the microscopic structure and heterogeneity of the replica leaf wax models based on the dominant wax types in the Schefflera elegantissima plant, namely C31H64 and C30H61OH and their binary mixtures. SED reveals grain microstructure in C31H64 crystals and nanoscale domains of chain-ordered lamellae within these grains. Moreover, nematic phases and dynamical disorder coexist with the domains of ordered lamellae. C30H61OH exhibits more disordered chain packing with no grain structure or lamellar domains. Binary mixtures from 0–50% C30H61OH exhibit a loss of grain structure with increasing alcohol content accompanied by increasingly nematic rather than lamellar chain packing, suggesting a partial but limited solid solution behaviour. Together, these results unveil the previously unseen microstructural features that may govern flexibility and permeability of leaf cuticles.
Analysis then turns to studying the impact of exposing these waxes to an external molecule, tris(2-ethylhexyl)phosphate (TEHP) commonly used as an adjuvant to promote uptake of crop protection molecules after topical application of a spray to a leaf. A combination of bulk techniques (X-ray diffraction (XRD), differential scanning calorimetry (DSC)) and electron microscopy techniques at different wax to TEHP concentrations suggest possible etching and dissolution mechanisms that disrupt the crystalline paraffin wax structures, with a greater effect seen in the interaction with the n-alkanol chains than the n-alkane chains. Wax crystal plane facet analysis by SED confirms the increased loss of material at crystal plane faces with a higher proportion of alcohol groups presenting at an exposed surface. In the paraffin wax solid solution system, spectroscopic techniques fail to differentiate the two wax components.
Finally, SED with elemental spectroscopy, energy dispersive X-ray spectroscopy, (EDS) is used to characterise the BA / TBA molecular alloying system prepared from ethanol solvents, where the two component molecules are similar except where a sulphur atom has replaced an oxygen atom in the TBA. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) suggest the components form a solid solution over the range of 20 – 70 % TBA content albeit with some hydrate formation too. EDS is used to quantify increasing TBA content up to ~60 % TBA, above which additional sulphur (TBA) content cannot be differentiated due to the increasing Bremsstrahlung background contribution it makes to the EDS.
The SED implementation of 4D-STEM has been shown to reveal microstructural features within a molecular solid solution that are not accessible by bulk techniques (such as changes in grain orientation, order and disorder at the nanoscale and dislocations). SED also has the potential to explore the importance of functional groups in solid solution formation, interaction with external molecules, and how impurities may affect solid solution form and stability (for example hydrate formation). Together this work opens up new prospects for the wider study of molecular crystal, solid solution systems.
