Novel metal-organic frameworks and polymer formulations for biomedical applications

Abstract

The research presented in this thesis aimed to develop new metal-organic framework (MOF) materials and MOF composites for biomedical applications.

New synthesis methods of CPO-27-M (M = Co, Mg, Ni, Zn) were explored with particular focus on the formation of single crystals. Low temperature syntheses showed formation of crystalline CPO-27-Zn down to 195 K. Single crystals of CPO-27-Mg and -Zn were afforded from a modulated solvothermal synthesis using salicylic acid, and an isomorph called UTSA-74 was obtained when benzoic acid was used. All three materials proved suitable for structural analysis through in-house single crystal X-ray diffraction (SXRD). The concept of modulation chemistry was employed to control the crystallite size and a novel mixed-linker synthesis approach yielded large single crystals of CPO-27-Ni. All materials displayed phase pure through PXRD, compositional analysis, TGA, and electron microscopy methods.

Large single crystals of CPO-27-Ni were used in synchrotron based in situ gas cell experiments to probe the adsorption of nitric oxide (NO). An efficient activation protocol was developed leading to a dehydrated structure after just 4 h. For the first time, single crystal structure models of CPO-27-Ni were presented of the as-synthesised, dehydrated, and subsequently NO loaded conformation.

A multifaceted study of the interactions between CPO-27-Ni and polyurethane (PU) was conducted to rationalise the NO release performance of composite films used as proxy for antibacterial coatings. From a range of MOF loadings (5, 10, 20, and 40 wt%) an optimal MOF loading of 10 wt% was identified, where highest amounts of NO with a potent bactericidal efficacy are released. Molecular dynamics simulations and FIB-SEM techniques revealed an excellent compatibility and connectivity between the MOF/PU interface. Reconstruction of the microstructure of a high MOF loading composite (40 wt%) showed that the MOF exhibits a highly connected network, which was proposed to contribute to a more tortuous gas transport. This also may be the reason for reduced NO efficiencies and tensile strengths seen in high MOF loading composites (20−40 wt%).

The Kolbe-Schmitt reaction was utilised for the synthesis of new functional linkers. Two methylated 4,6-dihydroxyisophthalic acids were obtained and used to generate new MOF materials for storage and release of NO. The 2,3-dihydroxyterephthalic acid linker was used to synthesise a new MOF system that has properties of isoreticular chemistry and is systematically named SIMOF-0, 1, 2, and 3 (St Andrews Isoreticular MOF). All four phases were characterised through SXRD. SIMOF-3 displayed an interesting, pillared crystal structure with indication of flexibility. A drug loading study using flutamide showed a prolonged release of the drug over the course of 72 h and solid-state NMR indicated that the drug may be adsorbed in the pore system of the MOF. SIMOF-1 was used as a precursor for other materials. In a ‘regeneration’ synthesis approach, a sample of SIMOF-1 was transformed to phase pure SIMOF-3.