Functionalised porous organic polymers for delivery of bioactive nitric oxide for potential therapeutic applications

Abstract

Exogenous delivery of NO has been shown to be effective at increasing wound closure rates and at combating a range of bacterial infections common in chronic wounds. Various delivery methods have been explored to exploit the potential of NO as a therapeutic agent, however each comes equipped with its limitations which inhibit practical utility.

In this thesis the development of porous organic polymers for the delivery of nitric oxide is documented. This work combines the diverse chemistry available to the development of organic polymers and the suitability of porous materials for gas delivery applications, to produce materials capable of releasing NO gas. A range of polymer series' have been developed via four different synthetic routes, resulting in different chemical structures, but each possessing a secondary amine or amide capable of post-synthetic modification (PSM) to incorporate N-nitroso or /V-diazeniumdiolate NO-donor. In addition, by substituting different monomers a variation in the BET surface area and pore volumes was achieved. Following PSM the NO release was determined in response to external stimuli and the rate of NO release and total NO released from each functionalised polymer was determined via the Griess method, and results were analysed based on porosity, NO-donor functional group and core chemical structure.

Key findings have shown that polyamide-based /V-diazeniumdiolates demonstrate considerable potential as NO-donors, as some released over 1600 pmol g^f NO; as amide /V-diazeniumdiolates have received minimal attention in the literature, this indicates a great undiscovered potential. Amides show more potential as /V-diazeniumdiolate NO-donors compared to /V-nitroso NO-donors, and the presence of amide and amine groups can enhance NO release from /V-nitroso based NO-donors. In this work, the synthesised N- nitroso polymers demonstrated NO release capacities ranging 1.9 pmol g_1to 277.0 pmol g1 and the /V-diazeniumdiolate polymers demonstrated NO release capacities ranging 50.8 pmol g1 to 1616.4 pmol g1. The main factors determining NO release capacity of the polymers was the type of NO-donor and core chemical structure. Other key findings include demonstrated controllable NO release of /V-nitroso based NO-donors, by control of UV irradiation trigger, and control over NO release by varying pore size. Using these findings can help to direct future design of novel NO-donors for potential therapeutic applications.

Date of Award	Dec 2019
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy & Engineering and Physical Sciences Research Council
Supervisor	Bo Xiao (Supervisor) & Stuart James (Supervisor)