Research Progress in Area 4 方向 ( 四 ) 課題進展 185 Abstract Marine natural products (MNP) are a rich source of bioactive agents that can direct future pharmaceutical design. The structures of many MNP from the Qian group showcase multiple challenges faced by state-of-the-art diffraction approaches, including poor crystal size and quality, instability due to desolvation, disorder and incorporation of different molecular forms. Prof. Williams’s team have successfully characterized a number of bioactive MNP compounds and the application of new instrumentation including a liquid galliumMetal Jet X-ray source and micro- Electron Diffraction will allow small and weaker samples to be studied in the coming year. Research Activities and Progress • Further developed capillary based microcrystallization methods; • Explored new crystallization tools: cocrystals crystalline host inclusion complexes; • Characterized marine natural products using single crystal X-ray diffraction; • Demonstrated use of micro Electron Diffraction for structure determination of natural products and their cocrystals. Key Findings • Combined capillary solvent diffusion and controlled evaporation (through mineral oil cap) effective for range of compounds down to 500 microgram scale; • NewmethodofmicroElectronDiffraction (microED) can be applied to sub-micron sized crystallites of natural products. MicroED determines structure of curcumin: hydroquinone (Cur:HQ) cocrystals prepared from flash spray drying; • Co-crystals applied to challenging flavonoid NP separation and purification in both natural (wogonin: oroxylin A) and synthetic (wogonin: chrysin) mixtures; • Beta-cyclodextrin as crystalline host allows ordered structure determination of natural product baicalein, gives advantage over Fujita’s crystalline sponge approach; • S-XRD determination of prenylated Griseocazine C2 with dimethylallyl and geranyl groups, confirms complex regio and stereochemistry (Fig 1); • Both ring open and cyclic forms of bioactive xanthones (F11, F24) and tetracyclines (Homoprejadomycin) well determined with absolute stereochemical assignment; • S-XRD determination of cyclic trithiazoletripeptide from a marine bacillus, with unnatural amino acids, (D-Phe, D-Ala) and possessing hydrophilic cavity (Fig 2). Research Output Publication 1 Trained personnel 4 Crystallization Methodologies for Structure Determination of Marine Natural Products Prof. Ian Williams The Hong Kong University of Science and Technology Fig. 1 Crystal structure of prenylated Griseocazine C2 confirming stereochemistry
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