Institute of Chemistry, Academia Sinica – Research
Directions
The research thrusts of the Institute are currently grouped along three major directions: materials chemistry, chemical synthesis and catalysis, and chemical biology. The current topics of materials sector include organic electroluminescent materials and devices, organic field-effect transistor materials and devices, photovoltaic materials and devices. The chemical catalysis and synthesis sector is focusing on the development of new synthetic methodology, drug discovery, carbohydrate chemistry, and the development of new catalytic systems for the generation of renewal energies and green fuels. The chemical biology program has made important advances in the delineation of bio-macromolecular structures and the development of new analytical platforms for disease detection and diagnosis.
Materials Chemistry: Organic Electronic and Optoelectronic Materialsy
Applications of organic optoelectronic materials and molecular engineering of nanomaterials are two major research directions under the materials division. Noticeable results include developments of blue fluorescent molecular materials for high performance organic light-emitting diodes, rational design of field-effective organic memory devices based on pentacene and gold nanoparticles, the very first stable organic thin film transistor based on single crystal of hexacene, rare single-walled metal–organic nanotube (MONT) with a large exterior wall diameter, the applications of metal-organic framework as optoelectronic materials, and a number of high performance materials for efficient solar energy harvesting devices such as dye-sensitized solar cells, perovskite solar cells, or organic photovoltaics. Researchers in this sector also develop stimuli-responsive materials, core-shell nanomaterials, and biomaterials. A recent report shows that a cell membrane–mimicking conducting polymer is capable to integrate biochemical and electrical stimulation to promote neural cellular behavior with great enhancement of neurite outgrowth on this conducting polymer.
Chemical Catalysis and Synthesis: Green Catalysis and Synthetic Methodology
In response to the increasingly demands of sustainable fuel and green synthetic technology, researchers in the organic synthesis and chemical catalysis divisions have strived to advance the development of cutting-edge technology for chemical transformations. The synthetic chemistry division of this sector focuses on the advances of synthetic methodology and drug discovery. The research topics under catalysis division is reconciling to catalysis relating to renewable energy. Major research directions in this sector include: (1) synthetic methodology: silyl ethers for hydroxy- directed nucleophilic acyl alkylation, microwave-assisted carbohydrate synthesis, smart fluorescent probes for bioorthogonal sugar labeling; (2) coordination chemistry: approaching unconventional catalysis via amino-NHC and carbodicarbene, unconventional porphyrin complexes for small molecule activations, engineering cytochrome P450 BM3 and alkane hydroxylase (AlkB) for alkane oxidations; (3) renewable energy catalysis: catalytic hydrogen evolution and mechanistic studies, encapsulated tricopper cluster for methane to methanol conversion, and novel catalysts for valorization of lignocellulosic biomass feedstocks.
Chemical Biology: New Material and Method towards Sustainable Health
Chemical biology division focus on the development of new material and methodology to explore the structure and function of macromolecules associated with cellular function or human diseases. The research activities are directed to unravel the underlying pathological mechanism and to derive new diagnostic and therapeutic strategies. Research topics in this division cover (1) development of smart biomaterials based on novel molecular principles; (2) chemical probe and advanced techniques in bio-imaging and structural biology; (3) drug discovery in cancer, infectious and neurodegenerative diseases; (4) development of structural biology techniques for infectious diseases, and (5) development of advanced proteomics strategies for biomarker discovery. The major achievements from the chemical biology group include the establishment of multiplexed quantitative strategy for membrane proteomics and post-translational modification for delineating disease mechanism and mining therapeutic targets discovery of amyloid fibrils induced from the TDP-43 in the Amyotrophic Lateral Sclerosis (ALS), and development of a photocontrollable probe to induce TDP-43 aggregates in live cells, mapping of the RNA exit channel on transcribing RNA polymerase II by FRET analysis, development of nano velcro chip to capture circulating tumor cells for liquid biopsy, construction of a near-infrared- activatable enzyme platform using an up-conversion nanoparticle to remotely trigger intracellular signal transduction.
Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of ReactivityAngew. Chem., Int. Ed. 2019, 58, 16775 –16779. Chun-Wei Chang, Chia-Hui Wu, Mei-Huei Lin, Pin-Hsuan Liao, Chun-Chi Chang, Hsiao-Han Chuang, Su-Ching Lin, Sarah Lam, Ved Prakash Verma, Chao-Ping Hsu*, Cheng-Chung Wang*
醣類分子在生物化學、藥物化學的產、學中均扮演非常重要的角色，然而受限於研究素材的取得不易，大大的侷限了研究的發展。雖然近幾年來有機合成策略提供了一個可能的解決方向，但在醣鏈結反應的開發過程中，仍然缺乏有效的準則來克服立體位向選擇性問題，此合成困境除大幅降低合成效率外，更導致醣類分子的開發極其緩慢。數十年來，雖然有大量的研究和論文發表，此一立體位向之控制仍舊是一個近乎隨機且聽天由命的過程。為克服此合成困境，本所王正中與許昭萍老師實驗室攜手合作，藉由有機合成及數值分析建立了一個新穎、簡易且方便的參數系統，此參數亦可提供AI系統作為演算的依據。未來全自動的醣類分子合成將可望成為常態。我們相信此一計畫帶來的成果能為醣化學和有機化學學界及產業界帶來革命性的影響和衝擊。此研究成果著重於醣予體(glycosyl donor)之量化以及大數據分析，藉由數值量化提供一個新的準則來解釋並預測複雜的醣鏈結反應，此結果跳脫傳統有機化學的泥淖，因而得到高影響係數 (Impact factor) 國際期刊的認同，已於近期發表於Angew. Chem., Int. Ed. 2019, 58, 16775 –16779。
Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.
