Abstract
In Chapter 2, we investigated the efficiency and kinetics of D-Ox/PA ROCOP catalysts, compared to the reported CrSalen, with a focus on catalysts known to efficiently catalyse sterically encumbered epoxides (for example aluminium trisphenolates and porphyrins). Strong performance was seen with an aluminium trisphenolate complex and the mechanism was explored through DFT modelling which provided insight into key reaction intermediates. Having further optimised the ROCOP of D-Ox with cyclic anhydrides, we showed the properties of the copolymer could be tuned by addition of an ELO crosslinker.In Chapter 3 this promising catalyst was shown to be efficient in catalysing the ROCOP of DOx and isothiocyanates. When using an Al porphyrin complex as catalyst, the reactivity could be tailored to form exclusively a non-polymerisable cyclic thionocarbamate byproduct. Four different isothiocyanate–D-Ox copolymers were reported, including a bifunctional isothiocyanate capable of crosslinking, to form thermally robust polymers (Td,5% > 228 °C) with a range of high glass-transition temperatures (76 – 134°C). The synthesis of di and triblock copolymers was possible by using difunctional (macro)initiators and by exploiting the living character of the ROCOP process, which allowed chain-extension by the ROP of lactide.
Chapter 4 takes the learnings from Chapter 2 into catalyst design, to develop the synthesis of new catalysts via the Kirsanov reaction, synthesising a family of seven aminophosphonium boron compounds. This synthetic method allowed for modular catalyst design and variation of the phosphorous electron shielding. These compounds were tested in the ROCOP of CHO and PA and the structure-activity relationship was explored, showing a clear correlation between electron density and catalyst selectivity. Catalyst design was also supported by DFT modelling. From these findings, a second, simpler organocatalysts was synthesised via the Kirsanov reaction. This was also shown to catalyse the ROCOP of CHO and PA without an initiator. Experimental findings were supported by DFT studies, probing the mechanism for initiation.
Finally, Chapter 5 details the post polymerisation functionalisation of two D-Ox copolymers (with phthalic anhydride and glutaric anhydride) to provide a controlled platform for amorphous solid dispersion (ASD) production with nifedipine and mefenamic acid. ASDs were optimised using microarray-3D printing and characterised in the bulk using DSC, Powder XRay Diffraction (PXRD) and Fourier Transform Infrared (FTIR) spectroscopy. Dissolution studies show the deprotected D-Ox copolymers are successful in improving the solubility of both drugs in water, rivalling the commercial standards.
| Date of Award | 25 Jul 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Antoine Buchard (Supervisor) & Matthew Davidson (Supervisor) |