Synthesis and characterisation of new metal-organic frameworks as carriers of antibacterial agents
Kelly, Aileen
Kelly, Aileen
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Publication Date
2024-04-18
Type
Thesis
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Abstract
Metal Organic Frameworks are highly porous, crystalline materials that have been used for a multitude of applications, with drug delivery and sensing at the forefront. These frameworks are extremely versatile and can be applied to multimodal applications, allowing for combined therapies and treatments to be developed. In this project, multimodal MOFs and mixed metal MOFs capable of antibacterial significance and a novel organic linker with the capability to form a theranostic MOF for luminescence and drug delivery was synthesised. Multi Drug Resistant Tuberculosis (MDR TB) is a disease that has become a threat to global health, killing 1.6 million people yearly thus being the second leading cause of human death via infectious disease. First and second line therapies are beginning to lose their efficacy as more drug resistant strains are on the rise. Additionally, the drugs that are currently on the market to treat MDR TB entail solubility issues, side effects and undergo rapid metabolism. To overcome the API issues alongside preventing the development of drug resistance, the multimodal MOFs, [Zn2(AZA)], [Mg2(AZA)] and [Co2(AZA)], were synthesised. These MOFs combined a prodrug organic linker azodisalicylic acid (AZA) as the organic component of the MOF, the antimicrobial metals Zn2+, Mg2+, Co2+ & Cu2+ and the APIs isoniazid, rifampicin, and ciprofloxacin. The MOFs successfully encapsulated isoniazid and ciprofloxacin and antibacterial assays were performed. A mixed metal MOF, [Zn2Cu2AZA], using the AZA prodrug linker and the metals Zn2+ and Cu2+ was synthesised. These metals were chosen in the hopes of achieving a controlled release of drug, while also combining the synergistic antimicrobial properties of each metal. These MOFs are currently undergoing MIC antibacterial studies to determine their efficacy. A stilbene-based ligand, cyanostilbene dicarboxylic acid, was synthesised with the potential of synthesising a MOF capable of both chemotherapeutic delivery and bioimaging. Alongside this, a second stilbene linker stilbene tricarboxylic acid was synthesised with the aim to produce a highly porous MOF capable of high drug loading and luminescence.
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NUI Galway