Metal‑Organic Frameworks (MOFs) have been intensely studied as novel materials for drug delivery and theranostic applications, where one radioactive drug is used to identify (diagnose) cancerous sites, and a second radioactive drug delivers therapy to treat the main tumour and any metastatic tumours. The iron-based MOF, called MIL-100 (Fe), can trap and release a large range of molecules in a controlled manner, including drug molecules. However, it is made via a toxic synthesis route that would hinder its use and large-scale production for commercial biomedical applications.
Barbara Souza from the University of Oxford, in collaboration with ISIS beamline scientist Dr Svemir Rudic, has used inelastic neutron scattering (INS) on TOSCA to reveal the details behind their recently developed 'green' synthesis of MIL-100 (Fe). Their water reconstruction method forms highly crystalline MIL‑100 (Fe) MOF material and eliminates the use of toxic mineralizing agents such as hydrofluoric acid that could affect the MOF's applicability in the biomedical field.
The work, which has been featured on the front cover of the ACS Sustainable Chemistry and Engineering issue, exploited the high sensitivity of INS to detecting the presence of hydrogen atoms, a key parameter in the reconstruction process, and focussed on the low‑frequency vibrational dynamics in the terahertz (THz) region of the MIL-100 (Fe) framework. The study not only unravelled details behind the reconstruction process, but also shed new light on the guest–host interactions arising from the system when a drug molecule is present, known as the drug@MOF system. Such interactions are central to establishing pathways to control the binding/release of drug molecules from MOFs as carriers.
The research team, led by Professor Jin‑Chong Tan from the University of Oxford, used their green synthesis route to produce drug@MOF composite systems, where drug guest molecules including 5-fluorouracil (5-FU), caffeine, or aspirin are encapsulated in the pores of the MIL-100 (Fe) host during the synthesis.
Schematic
representation of the water reconstruction method. A mechano-chemical approach was
used for the synthesis of low crystallinity MIL-100 (Fe). Subsequently, the reconstruction
process was applied to enhance material crystallinity and for the entrapment of
different drug molecules within the MOF pores. Colour scheme: O in red, C
in black, H in grey, Fe in orange.
The team demonstrated the use of INS spectroscopy as a unique approach for studying the guest‑host interactions by determining the vibrational dynamics of the MIL-100 (Fe) phase and its guest-encapsulated composites. This work could be applied to the large-scale synthesis of mesoporous MIL-100 materials for future commercialisation, providing a new approach to the eco-friendly and scalable synthesis of mesoporous MIL-100 (Fe) and guest@MIL-100 systems.
“The high sensitivity of INS to the presence of hydrogen atoms allowed us to fully understand the mechanism behind the reconstruction process, which involves the continuous deprotonation of the organic ligand present in the MOF." Explains Ms Souza; “The study of modifications in the THz lattice dynamics of our drug@MOF systems helped to shape our understanding of the interactions within the systems, which is highly important factor in the moderation of the drug release process".
Left: TOSCA
beamline scientist Svemir Rudic with researcher Barbara Souza
The team has demonstrated how the use of this novel in situ reconstruction method permits the maximization of drug loading, surpassing values achieved with conventional encapsulation techniques (i.e. immersion of the host MOF into a saturated drug solution) and bringing it closer to theoretical loading capacities estimated for MIL‑100 (Fe). They are now focusing on the production of different guest@host composite systems and their comparison of the reconstruction approach with other in situ mechano-chemical based methods.
Further Information
Multifunctional Materials and Composites (MMC) Laboratory, Oxford University
The full paper can be found at: B.E. Souza, A.F. Möslein, K. Titov, J.D. Taylor, S. Rudic, and J.C. Tan*, "Green Reconstruction of MIL‑100 (Fe) in Water for High Crystallinity and Enhanced Guest Encapsulation", ACS Sustainable Chemistry & Engineering, 8, 8247-8255 (2020). DOI: doi.org/10.1021/acssuschemeng.0c01471
Souza's research team has demonstrated in 2019 the use of INS spectroscopy to examine the encapsulation of the anti‑cancer drug 5‑FU within the host framework (HKUST‑1).
