dc.description.abstract | Metal-organic Frameworks (MOFs) are a versatile and ultra-porous class of materials composed of metal nodes and organic linkers, where the physicochemical properties of the MOFs can be controlled through careful selections of the inorganic or organic precursors. Therefore, MOFs show promise for a wide range of applications ranging from gas capture to biotechnology etc. Especially, the recent progress in water-based synthesis of Zeolitic Imidazolate Framework (ZIFs) opens a potential avenue for solving hazardous synthesis of MOFs. In our previous report, we proposed the green synthesis of ZIF-90 under aqueous and further demonstrated a de novo approach for embedding enzyme in structure of ZIF-90 by introducing enzyme during the MOFs synthesis. This fact imparts the functionality of micro-porosity in ZIF-90 to enzyme for shielding the bigger size of protease and allow the smaller substrate to diffuse in for enzyme catalysis.
In this thesis, we aim to study the merit provided by the de novo approach. We provide an additional benefit of de novo approach that the enzyme immobilized using de novo approach could shield the conformation of enzyme from unfolding, thus its biological function can be maintained under a wider range of conditions. We proposed this enhanced stability should be arisen from confinement of the enzyme molecules, wherein enzymes stay in additional mesoporous cavities formed by using enzyme as template. A fluorescence spectroscopy study shows that the structural conformation of the embedded enzyme with less change under denaturing conditions than free enzyme. Remarkably, we develop the concept of the MOFs Chemical Biology for probing on relationship between structural conformation and biological activity of the enzyme, and we try to expand the diversity of the de novo approach by exploring the other MOFs with larger aperture, which is allowed for diffusion of co-factors and co-enzymes in different sizes such as ATP and NADH. In this regard, we try to explore the synthesis UiO-66 in water-based system and mainly focus on their formation mechanism for realizing the syntheses of other MOFs material in aqueous solution. We suggested the solubility of organic linkers in aqueous solution can be the major concern in attempt to achieve a successful synthesis and provide ways to conquer the challenges.
Further, we continued to expand the advantages of green synthesis in ZIF-90 with reduced particles size. The nature of green synthesis repels the risk of toxic solvents still being present within the particles, thus shows their potential as a drug carrier. Also, the functionality of carriers provides methods to control drug release, yet the reported modifications suffer from largely reduced in merits, such as porosity. Thus, we demonstrated a green-based and simple method for the organic functionalization of crystalline nano-sized ZIF-90 (nZIF-90) as well as at least 25% micropore volume maintained via post-synthesis modification using optimal reactant molar ratios. The structural integrity of the original compound was preserved. The cytotoxicity of the nZIF-90 and nZIF-90 transformers around 30~70 µg/mL are moderate in comparison of those other organic and inorganic drug carriers. Thus, nanoscale MOF particles with new functionalities provide a new generation of carriers for drug delivery.
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