Abstract
Metal-organic frameworks (MOFs) represent a highly adaptable class of materials with significant potential in various bio-related applications. In this thesis, two specific applications have been focused on: drug overdose treatment and glucose sensing. The utilisation of Al(OH)(1,4-ndc) (ndc = 1,4-naphthalenedicarboxylate) was explored and evaluated to address these applications, following a previous initial computational screening. Additionally, the potential of a defective UiO-66 MOF to interact with sodium ibuprofen was investigated, offering sustained loadings under gastrointestinal conditions. For the glucose sensing application, Al(OH)(1,4-ndc) was primarily employed.Before delving into these applications a 50 mg to 800 mg scaled-up synthesis of Al(OH)(1,4-ndc) was conducted to enhance the synthesis efficiency. This involved increasing the reagent-to-solvent ratio while keeping the solvent volume, temperature, and apparatus setup constant. In the efforts to scale up the synthesis procedures explored in this thesis, the 5-fold scale-up of Al(OH)(1,4-ndc) in water marked the highest scale-up possible while preserving the MOF's crystallinity.
A combination of computational simulations and experimental work were employed to investigate the adsorption of ibuprofen and paracetamol from aqueous solutions. Computational predictions of the affinity and capacity of these drugs in defective Al(OH)(1,4-ndc) and UiO-66 were conducted using grand-canonical Monte Carlo simulations. While ibuprofen displayed higher affinity, paracetamol exhibited higher capacity. The introduction of defects by substituting ligands with capping groups into Al(OH)(1,4-ndc) either decreased or minimally affected the affinity of the target drugs. In contrast, the affinity and capacity of drugs increased with the degree of deficiency in UiO-66. Experimental validation of sodium ibuprofen and paracetamol adsorption was carried out in both pH-neutral and acidic solutions. Al(OH)(1,4-ndc) synthesized in N,N-dimethylformamide (DMF) exhibited defects and outperformed Al(OH)(1,4-ndc) synthesized in H2O in the adsorption of sodium ibuprofen and paracetamol. Intriguingly, the Al(OH)(1,4-ndc) synthesized in H2O lost its linker in pH-neutral water, while the DMF-synthesized MOF lost the linker in acidic solutions. Defective UiO-66 displayed substantial uptakes of sodium ibuprofen due to carboxylate substitution for a capping monocarboxylate. This chemisorption aspect is often overlooked in computational screening but plays a critical role in practical conditions.
Glucose oxidase was immobilised on the surface of Al(OH)(1,4-ndc) synthesized in water for glucose sensing via colorimetric and electrochemical detection. Although the immobilised glucose oxidase remained active and was detected colorimetrically to a concentration of 0.02-0.08 g L-1, when utilised as an electrode modified with the enzyme for electrochemical detection, the MOF showed no amperometric response to glucose. Introducing polydopamine to the composite aimed to enhance sensor sensitivity, but the modified electrode still showed no amperometric response to glucose. The use of this specific MOF as an immobilisation material for enzyme-based can be further developed for colorimetric detection, and further developments are required for electrochemical glucose sensing.
| Date of Award | 22 May 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Matthew Lennox (Supervisor), Hannah Leese (Supervisor) & Andrew Burrows (Supervisor) |