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.
建立以紅外線活化的激酶-上轉換粒子平台以控制細胞內信號傳遞
Construction of a Near-Infrared-Activatable Enzyme Platform to Remotely Trigger Intracellular Signal Transduction Using an Upconversion NanoparticleACS NANO 2015, 9, 7041
Hua-De Gao, Pounraj Thanasekaran, Chao-Wei Chiang, Jia-Lin Hong, Yen-Chun Liu, Yu-Hsu ChangHsien-Ming Lee
利用光來活化生物分子可以達到遙控的目的並且有極高的時間及空間上的控制性， 是化學生物學家重要的實驗工具。但是傳統的方法需要以紫外線光照，因此在進行細胞實驗時，無法屏除來自紫外線對生物的傷害及干擾。此研究利用鑭系元素的上轉換粒子與負責磷酸化的激酶交聯之後，成功的達成用紅外線來控制光化學生物學（信號傳遞分子磷酸化）反應，並進一步控制生物上現象，如細胞行為。此一平台也提供了另一波長來控制光化學反應，使得在活體內可進行兩種光化學反應，這些都是以前傳統紫外光光解化學所做不到的。
Photoactivatable (caged) bio-effectors provide a way to re-motely trigger or disable biochemical pathways in living organisms at a desired time and location with a pulse of light (uncaging), but the phototoxicity of ultraviolet (UV) often limits its application. In this study, we have demonstrated the near-infrared (NIR) photoactivatable enzyme platform using protein kinase A (PKA), an important enzyme in cell biology. We successfully photoactivated PKA using NIR to phosphorylate its substrate, and this induced a downstream cellular response in living cells with high spatiotemporal resolution. In addition, this system allows NIR to selectively activate the caged enzyme immobilized on the nanoparticle surface without activating other caged proteins in the cytosol. This NIR-responsive enzyme-nanoparticle system provides an innovative approach to remote-control proteins and enzymes, which can be used by researchers who need to avoid direct UV irradiation or use UV as a secondary channel to turn on a bio-effector.
Figure 1. Crosslinked caged kinase / nanoparticle, upon the NIR irradiation, can upconvert the NIR to UV, and activate the caged kinase on its surface to restore its kinase activity.
Figure 2. The spatial resolution of this technique can reach to mm level (yellow region shows stress fiber unbundled by NIR light.