Mechanochemically synthesised metal-organic frameworks as nanovehicles for drug delivery

Abstract

In recent years MOFs have attracted a lot of attention for their permanent porous properties. MOFs are traditionally synthesised using a solvothermal synthesis method, but a “green” synthesis method has recently emerged, mechanochemical synthesis, which can produce MOFs using a fraction of the solvent compared to solvothermally synthesised counterparts. MOFs have the potential to revolutionise several fields, most notably gas-storage and catalysis. In this thesis the potential drug loading applications of MOFs which have been mechanochemically synthesised are explored. Mechanochemical synthesis has been used to prepare MOF-74-Zn, Zn2C8O6H2, a porous metal-organic framework. Several novel crystalline intermediates, C14H20N2O8, C14H22N2O10Zn(α), C14H22N2O10Zn(β) were found to form during mechanochemical synthesis prior to MOF-74. Their structures have been characterised by powder and single-crystal X-ray diffraction. The properties of mechanochemically-synthesised MOF-74-Zn have been investigated using analytical, spectroscopic and powder X-ray diffraction methods to compare to conventionally synthesised MOF-74. The potential of MOF-74-Zn as a vehicle for drug delivery applications has been investigated. Reported here is the drug loading and unloading of MOF-74-Zn with ibuprofen. The maximum ibuprofen loading of 0.29 g/g of ibuprofen per gram of MOF-74-Zn is reported and the ibuprofen-MOF interactions have been investigated using solid-state NMR (SS-NMR) and inelastic neutron spectroscopy (INS). By adopting a similar synthetic approach to that used for MOF-74, a novel isoreticular framework based on MOF-74-Zn has been prepared (IR-MOF-74-Zn). This new II framework has the same topology and pore shape as MOF-74-Zn but is synthesised with a larger organic linker, 4,4’-oxalylbis(imino)]bis(2-hydroxybenzoic acid). The linker was used to produce a framework with significantly larger potential surface area than MOF-74 with estimated pore diameters of 22 A. As with MOF-74, crystalline intermediates form during synthesis. Three IR-MOF-74-Zn intermediates have been found and partially characterised using X-ray diffraction methods. The crystal structures of 2,5-dihydroxyterephthalic acid (C8H6O6) and its potassium salt (C8H6O6K(H2O)) are also reported. Additionally, the crystal structure of the DMF solvate of 4,4’-oxalylbis(imino)]bis(2-hydroxybenzoic acid (C16H12N2O8(C3H7O)2) and its zinc paddlewheel coordination polymer, (Zn2(C2H3O2)2C16H12N2O8(C3H7O)2), have also been characterised