Results

In this section we list 9 most significant research publications of IoC between 2010 and 2015 in a format of either group summary or individual publication abstract. Noticeably, these selected highlights have subjects distributed evenly among three major research divisions. Worth mentioning is that three out of the 9 research highlights are research results from our young generations joined IoC after 2009.

1. The Synthesis, Crystal Structure and Charge-transport Properties of Hexacene

Acenes are a class of aromatic hydrocarbons composed of linearly fused benzene rings. They have been effectively used in a wide range of opto-electronic devices, such as organic field effect transistors (OFETs), organic photovoltaic cells (OPVs), organic light-emitting diodes (OLEDs), and organic chemosensors,¬ etc. Recently Dr. T. J. Chow developed new synthesis routes for higher acenes using stable and soluble precursors, which generate these structures on demand by either heating or irradiation of light (Acc. Chem. Res. 2013, 46, 1606). Using these methods, the derivatives of hexacene (Nature Chem. 2012, 4, 574), pentacene (Chem. Commun. 2012, 48, 6148), and tetracene (J. Mater. Chem. 2012, 22, 13070) were successfully prepared. Many of them displayed remarkable OFET characteristics. In the Nature Chemistry article, we used a physical vapor transport method to collect platelet-shaped crystals of hexacene from a monoketone precursor. The crystals are stable in the dark for a long period of time under an ambient condition. In crystal lattice the molecules are arranged in herringbone arrays, similar to that of pentacene. An OFET device made with a single crystal of hexacene displayed the highest hole mobility 4.28 cm2 V-1 s-1 with an on/off ratio of 1 × 10E5 and a threshold voltage of 37 V. These devices can function under an ambient environment for more than 19 days. This result is instructive to further explorations on other higher acenes.


Journal Papers:
Tashin J. Chow*, Nat. Chem., 2012, 4, 574-578

2. 2,6-Conjugated Anthracene Sensitizers for High-Performance Dye-Sensitized Solar Cells

Metal-free dyes (Ant1 to Ant4) containing a 2,6-conjugated anthracene unit in the spacer have been synthesized. The conversion efficiency (7.52%) of the dye-sensitized solar cell using Ant3 as the sensitizer reached ~90% of the standard N719-based cell (8.41%). Co-sensitized DSSC using Ant3 and a near-IR dye (SQ2) exhibited an improved efficiency of 8.08%. With addition of co-adsorbent, CDCA, the cell efficiency (9.11%) of Ant3-based DSSC surpassed that of the N719-based standard cell. An even higher efficiency of 10.42% was achieved under weak light irradiation.


Journal Papers:
Jiann T. Lin * and Kuo-Chuan Ho*, Energy Environ. Sci, 2013, 6, 2477–2486

3. Large Enhancement in Neurite Outgrowth on a Cell-Membrane-Mimicking Conducting Polymer

Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. In this research article, we develop a cell membrane–mimicking conducting polymer possessing several attractive features. This polymer displays high resistance toward nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behavior. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur upon it.


Journal Papers:
Hsiao-hua Yu*, Nat. Commun. 2014, 5, 4523

4. Approaching Unconventional Chemical Puzzles and Catalysis via Conventional Ligand Design in Amino-NHC and Carbodicarbene

Ong group has been at forefront of designing a myriad of amino-nitrogen heterocyclic carbene (NHC) and carbodicarbene frameworks and investigating of their fundamental chemical reactivities, which they have made numerous significant contributions and innovations in the context of molecular catalysis, synthetic chemistry, medicinal and main group elements. The ability of catalyst to direct the green synthesis for complex molecules from simple starting materials is epitomized by the vibrant theme of the C-H bond activation. Dr. Ong has systematically established a revolutionary approach in exploiting synergistic effect between main and transition metal to promote efficient selective C-H activation (Scheme 1). The detailed work could be found in the J. Am. Chem. Chem., 2010. At the same time, the amazing catalytic reaction performed by enzyme has inspired Ong group to endeavor the first special acyclic pincer bis(pyridine)carbodicarbene. Such Pd metallic complex supported by this highly electron rich pincer ligand is a very active catalyst for Heck-Mizoroki and Suzuki-Miyaura coupling reactions (Scheme 2, Angew. Chem. Int. Ed. 2015). Finally, Ong also have discovered the formation of a hitherto unknown three-coordinate dicationic hydrido boron complex with unique bonding environment (Scheme 3, J. Am. Chem. Soc., 2014). Supporting ligand carbodicarbene gave unprecedented reaction with BH3 without using more highly electrophilic Lewis acid precursors. A reaction behavior not observed for other common NHC ligands. These results pave the way for future studies in highly electrophilic Lewis acid chemistry with interesting potential applications in organic synthesis and catalysis.


Journal Papers:
Chao-Ping Hsu* and Tiow-Gan Ong*, J. Am. Chem. Chem., 2010, 132, 11887-11889
Tiow-Gan Ong* J. Am. Chem. Soc., 2014, 136, 914-917
Chao-Ping Hsu* and Tiow-Gan Ong*, Angew. Chem. Int. Ed. 2015, 54, 2420–2424

5. Lithiation of a Silyl Ether; Formation on an ortho-Fries Hydroxyketone

OThe hydroxy-directed nucleophilic acyl alkylation of hydroxyarylamides and salicylic acid through an anionic Si→C alkyl migration was developed using a simple reagent combination of LDA and chlorosilane (Fig. 1). The transformation involves (1) a complex-induced proximity effect (CIPE) in the deprotonation step, (2) an intramolecular Peterson type reaction of the resulting α-silyl carbanion with the amide group, and (3) fission of the final β-oxygenated silyl intermediate (Scheme 1). This reaction giving silyl ether a new role in organic synthesis was further developed for application to an extended anionic Snieckus-Fries rearrangement (Fig. 1). The exceptional functional group transformations achievable using a simple reagent combination of LDA and chlorosilane renders these reactions highly valuable for the synthesis of natural products and medicinally important compounds, such as the PI3K inhibitor LY294002.


Journal Papers:
Rong-Jie Chein*, Angew. Chem. Int. Ed. 2014, 53, 9026-9029

6. Large-scale Determination of Absolute Phosphorylation Stoichiometries in Human Cells by Motif-Targeting Quantitative Proteomics

Protein phosphorylation is one of the most critical post-translational modifications to regulate cellular function. Direct measurement of the phosphorylation stoichiometry at the proteome scale provides a system view for signaling pathway activation and unambiguously reveals whether the signal-induced alteration is regulated by upstream kinase/phosphatase activity or by transcriptional regulation to modify protein abundance. Until now, current quantitative proteomic approach can only be used for measurement of relative quantitation of phosphorylation events without information about the stoichiometry of modification within proteins. We have developed a motif-targeting quantitative proteomic approach (Figure A) to successfully measure the phosphorylation stoichiometry from more than 1000 phosphorylation sites including 366 low abundant tyrosine phosphorylation sites from lung cancer cell. To our knowledge, this approach reveals the first large-scale measurement on the basal level of phosphorylation stoichiometry in a single state human phosphoproteome. On the application of phosphorylation stoichiometry profiling of drug resistance/sensitive lung cancer cells, such quantitative information illuminated that the post-translational phosphorylation changes are significantly more dramatic than those at protein as well as mRNA levels. Further analysis suggested potential drug-targeting proteins in the kinase-substrate network associated with acquired drug-resistance (Figure B). We expected that this newly developed approach will have wide applications to provide system-wide maps of protein phosphorylation stoichiometry for either single or multiple cellular states under physiological or pathological regulation.


Journal Papers:
Yasushi Ishihama* and Y.-J. Chen*, Nat. Commun. 2015, 6, 6622

7. Programming Thermoresponsiveness of NanoVelcro Substrates Enables Effective Purification of Circulating Tumor Cells in Lung Cancer Patients

Circulating tumor cells (CTCs) are cancer cells that break away from tumors and travel in the blood, looking for places in the body to start growing new tumors called metastases. Capturing these rare cells allows doctors to detect and analyze a patient’s cancer to give insight into personalized treatment design for each patient. In the Smart Organic Materials Laboratory at Academia Sinica, Dr. Hsiao-hua Yu and Hsian-Rong Tseng from the California Nanosystems Institute at UCLA have developed a way to capture CTCs from blood samples – a liquid biopsy – and then release them from the surface with great cell viability using an invention called the Nano Velcro chip. This allows the scientists to examine the CTCs and analyze their genetic features.
The thermoresponsive nano-velcro CTC purification system, developed by Yu and his colleagues allows them to raise the temperature to adhere the cells, then lower it to release them. This method makes the process for extracting CTCs much more efficient and cost-effective at a time in a patient’s life when doctors need as much information as possible and as quickly as possible. Moreover, mutational genetic analysis is successfully demonstrated to monitor the disease evolution of a sample lung cancer patient. This shows the translational value of the device in managing non-small cell lung cancer with underlying mutations.


Journal Papers:
Zunfu Ke*, Shuang Hou*, Hsiao-hua Yu*, Hsian-Rong Tseng*, ACS Nano, 2015, 9, 62–70

8. Induction of Amyloid Fibrils by the C-Terminal Fragments of TDP-43 in Amyotrophic Lateral Sclerosis

Joseph’s group has been focusing on the protein misfolding in neurodegenerative disorders, especially in Amyotrophic Lateral Sclerosis (ALS), since he joined the Institute of Chemistry. This was a new and hot topic for the aggregation of TDP-43 had just been identified in the ALS patient in 2006. Within 2010-2015, Joseph’s team was the first to report on the amyloid properties of the TDP-43 C-terminus peptides (J. Am. Chem. Soc. 2010) by applying novel chemical and biophysical strategies (Fig.1). This paper is highly cited and being highlighted in the 2010 Significant Research Achievements of Academia Sinica and selected in 2010 Science and Technology Yearbook of Republic of China. Later on, by applying different cell-free system and liposome assays, they have also disclosed the prion-like properties of the TDP-43 peptide fragments (Chem. Commun. 2013). This paper is again highlighted in the 2013 Significant Research Achievements of Academia Sinica. Recently, by the close collaboration with his colleague, Dr. Hsien-Ming Lee, they found that TDP-43 fragments may impair the membrane and served as a seed to induce TDP-43 aggregations in the neuron cell (Chem. Commun. 2015) (Fig.2). All these results from Joseph’s group have provided important insights of how intrinsically-disordered domains in TDP-43 correlated with aggregation and amyloid properties, which may shed light on the TDP-43 misfolding in ALS as well as in other misfolding diseases. With his efforts in the TDP-43 proteinopathy, he has also been awarded with the 2012 Excellent Young Scholar Award from the Taiwan Chemical Society.


Journal Papers:
Joseph J.-T. Huang*, J. Am. Chem. Soc. 2010, 132, 1186-1187

9. Regulation of Mammalian Transcription by Gdown1 through a Novel Steric Crosstalk Revealed by cryo-EM

In mammals, a distinct RNA polymerase II form, RNAPII(G) contains a novel subunit Gdown1 (encoded by POLR2M), which represses gene activation, only to be reversed by the multisubunit Mediator co-activator. Here, we employed single-particle cryo-electron microscopy (cryo-EM) to disclose the architectures of RNAPII(G), RNAPII and RNAPII in complex with the transcription initiation factor TFIIF, all to ~19 Angstrom. Difference analysis mapped Gdown1 mostly to the RNAPII Rpb5 shelf-Rpb1 jaw, supported by antibody labeling experiments. These structural features correlate with the moderate increase in the efficiency of RNA chain elongation by RNAP II(G). In addition, our updated RNAPII–TFIIF map showed that TFIIF tethers multiple regions surrounding the DNA-binding cleft, in agreement with cross-linking and biochemical mapping. Gdown1’s binding sites overlap extensively with those of TFIIF, with Gdown1 sterically excluding TFIIF from RNAPII, herein demonstrated by competition assays using size exclusion chromatography. In summary, our work establishes a structural basis for Gdown1 impeding initiation at promoters, by obstruction of TFIIF, accounting for an additional dependent role of Mediator in activated transcription.


Journal Papers:
Averell Gnatt* and Wei-Hau Chang*, EMBO J., 2012, 31, 3575-3587