10^th Annual Chemistry Congress October 18-19, 2017 Osaka, Japan

Wen Yun Hsueh has completed her Master’s degree from the Department of Applied Chemistry at National Chiayi University, Taiwan. Currently she is pursuing PhD research at the same institute. Her research interests include chemistry and synthesis of heterocycles as anti-cancer agents.

This poster presents the discovery of orally active TAI-95 tosylate, the Nek2/Hec1 inhibitor in clinical trial for cancer therapy. Designed and optimized from lead compound 4-aryl-N-phenylcarbonyl-2-aminothiazole, TAI-95 tosylate shows ~100-fold improved in vitro potency (IC50: 14.8-21.1 nM), high oral AUC (66.6 μM•h) and good oral bioavailability (77.4%). Oral administration of TAI-95 shows significant in vivo activity on mice bearing human liver cancer Huh-7 and breast cancer BT474, MDA-MB-231 and MCF7 xenografts. It disrupts the interaction of Hec1 and Nek2 and leads to degradation of Nek2, chromosomal misalignment and apoptotic cell death, which are the cellular events of Hec1/Nek2 inhibition. TAI-95 showed synergistic activity in selected cancer cells with Doxorubicin, Paclitaxel and Topotecan and is inactive for non-cancerous cancer cells, a panel of kinases and hERG with IC50 values greater than 10 μM. Currently, it was in phase-I clinical trial to study its maximum tolerated dose, pharmacokinetics and responses on patients with advanced refractory solid tumors.

Myeong Eun Heo has completed her graduation in Chemistry and currently pursuing her Masters at Yeungnam University, Republic of Korea.

The binding mode of a pyrene-porphyrin hybrid, (1-pyrenyl)-tris(N-methyl-p-pyridino) porphyrin (Py-TMPyP), to DNA and its photo-physical properties are important for understanding photodynamic function of porphyrin derivatives in the environment of DNA. In order to better understanding of their properties we employed polarized spectroscopy, fluorescence techniques and transient absorption spectroscopy. Circular Dichroism (CD) of the Py-TMPyP hybrid in the soret region consists of two positive and one negative band when bound to DNA and polyd[(A-T)2]. In case of polyd[(G-C)2] shown one negative and one positive band like bisignate. The CD in the pyrene absorption region was positive. The shape of the CD spectrum did not support the intercalative binding mode of TMPyP, which produces a negative CD band when it intercalates between the base-pairs in the absence of the pyrene moiety. Linear Dichroism (LD) revealed very small signal in the Soret region, which is also against the intercalation of the TMPyP moiety to DNA. The emission intensity of the Py-TMPyP hybrid in the porphyrin emission region in an aqueous solution is negligible when excited at the pyrene absorption region. On the other hand, a large enhancement in the fluorescence intensity was observed when bound to DNA and polyd[(A-T)2], suggesting energy transfer from the excited pyrene moiety to TMPyP when bound to DNA and polyd[(A-T)2]. This suggests that native DNA and AT context polynucleotides are essential for energy transfer. However, in case of bound to polyd[(G-C)2] was shown extremely weak intensity in the porphyrin emission region. This result is probably the result of oxidative damage to GC base by singlet oxygen produced by photo-physical reaction process. Two fluorescence decay times were observed for the Py- TMPyP in an aqueous solution, which were 0.78 ns and 4.8 ns. The latter component can be assigned to the TMPyP. The short component conceivably represents the charge transfer species between the pyrene and porphyrin moiety. Both decay times became longer when associated with DNA, representing a change in the environment and/or conformation of the Py-TMPyP hybrid upon binding to DNA. The Py-TMPyP hybrid in aqueous solution produced two decaying species in the transient absorption spectrum. This is in contrast to TMPyP, which did not produce any transient absorption spectrum. These two decay times also became longer when bound to DNA.

Minkyu Park has completed his Master’s degree in Chemistry from Yeungnam University, Republic of Korea.

Recently, active research and development of rare earth materials has been ongoing for applications in high-technology products. Rare earth materials is variety of advantage properties, such as highly efficient luminescence from visible to Near Infrared (NIR), strong magnetic susceptibility and thermal conductivity. Among the trivalent lanthanides, Pr, Nd, Ho, Er and Tm ions emit NIR luminescence. However, the luminescence are associated with f→f electronic transitions, forbidden by electric dipole moment but weakly allowed by induced crystal-field potential. Previously, to overcome this problem, we introduced a Schiff base (L=N,N’-bis(salicylidene)-3,6-dioxa-1,8-diaminooctanato) as a sensitizer to Eu (III) complex system. In this study, the synthesis and characterization of four Ln (III) complexes with mixed Schiff base (L) as a main ligand and 1, 10-phenanthroline (phen) as an auxiliary ligand. The Ln (III) complexes excited at near-UV light produced in sensitized NIR luminescence via the energy transfer from L to the Ln (III) ions. Based on the observed photo-physical properties of the Ln (III) complexes and the reported energy-levels of the free Ln (III) ions, we proposed the resonance energy-transfer pathway of the sensitized NIR luminescence

Min Ik Kwak has completed his graduation and currently pursuing Postgraduate studies from Yeungnam University majoring in Biophysical Chemistry

The binding modes of o-, m- and p-trans-BMPyP and DNA were investigated by using spectroscopy properties. We also compared the binding modes of the cationic porphyrin with the position and number of the periphery cationic methyl pyridine ions. When o-, m- and p-trans-BMPyP was bound to DNA, the absorption spectrum showed red shift and hypochromism compared with the absorption spectrum of DNA free cationic porphyrin and m-trans-BMPyP-DNA showed the greatest. In the case of o- and p-trans-BMPyP-DNA at all concentration ratios as a result of CD spectrum, positive and negative bisignate absorption bands in Soret region of porphyrin and two negative absorption bands of m-trans-BMPyP-DNA were observed. The results of the LDr spectra show that the Soret absorption band of porphyrin is small and that m- and p-trans-BMPyP-DNA has a positive absorption value when compared with the absorption band of the light absorbing region of DNA. Considering these various spectroscopic properties, o-, m- and p-trans-BMPyP are far from the insertion mode when they are bound to DNA. The comparison of the binding modes with TMPyP with 4 number of peripheral cationic methyl pyridine ions of cationic porphyrin showed that the position of the periphery cationic methyl pyridine ion is important but the number is the most important factor to be inserted into the DNA base pair. In other words, o-TMPyP in the case of TMPyP with 4 number of periphery cationic methyl pyridine ions of cationic porphyrin exhibits outside binding mode which interacts with DNA phosphate due to steric hindrance of periphery cationic methyl pyridine ion and m- and p-TMPyP was inserted into the DNA base pair. However, trans-BMPyP with the number of two cationic methyl-pyridine ions in cationic porphyrin was found to be an outside binding mode that interacted with DNA phosphate or to bind to the groove.

Jeon Bo Ram has completed her graduation and is currently pursuing Postgraduate studies from Yeungnam University majoring in Biophysical Chemistry.

Ruthenium (II) polypyridyl dimer containing the large planar aromatic bridging ligands [μ-(tpphz)(phen)4Ru2]4+ (phen=1,10-phenanthroline, tpphz=tetrapyrido[3,2-a:2',3'-c:3", 2"-h:2"', 3"'-j] phenazine, bis-Ru-tpphz) have been synthesized and characterized by elemental analysis, 1H NMR. The binding mode of the newly synthesized bis-Ru-tpphz to DNA was compared to those of the bis-Ru-bip and bis-Ru-tatpp complexes. The structure of connecting bridge of latter two bis-Ru complexes is different. Absorption and reduced linear dichroism spectrum reveal that the planar linker moiety of the bis-Ru-tatpp complex is inserted between the DNA base-pairs in spite of steric hindrance originated from its large ruthenium ligand part while the bis-Ru-bip complex which has flexible linker binds at the groove of DNA. The binding mode of the bis-Rutpphz complex which has fused shorter bridge ligands than bis-Ru-tatpp complex is in contrast with the other two complexes. Also in the presence of ethidium bromide, a classical intercalator, binding of bis-Ru-tpphz complex to DNA did not interfere with ethidium binding. The bis-Ru-tpphz complex binds either at the groove of DNA or to the negatively charged phosphate group: Intercalative binding was prohibited due to either short bridge structure or steric hindrances from the phenanthroline ligand. In conclusion, the structure of the bridge of bis-Ru(II) complex takes an important role to determine the binding mode of these compounds to DNA and in order to have the mode of insertion, the bridge ligand structure must be not only fused planarity, but also their distance should be long enough.

Ye Sol Oh has completed her undergraduate studies and currently pursuing Masters from Yeungnam University, Republic of Korea.

Meso-tetrakis (N-methyl pyridinium-4-yl) porphyrin (TMPyP) intercalates between the base-pairs of DNA at a low [TMPyP]/[DNA base] ratio in aqueous solutions and molecular crowding conditions, which is induced by the addition of poly Ethylene Glycol (PEG). Studied DNA binding drugs, including TMPyP, 9-AA (aminoacridine), EB (Ethidium Bromide) and DAPI (4’, 6-diamidino-2-phenylindole) showed similar binding properties in the presence or absence of PEG molecules which is examined by circular and linear dichroism. According to the LDr (reduced Linear Dichroism) results of the binding drugs examined in this work, PEG molecules induced no significant change compared to their binding properties in aqueous buffering systems. These results suggest that the transition moments are not expected to be perturbed significantly by PEG molecules. In this study, the experimental conditions of PEG 8000 were maintained at 35% (v/v) of total reaction volume, which is equal to the optimal molar concentration (0.0536 M as final concentration for PEG 8000) to maintain suitable cell like conditions. Therefore, there was no need to focus on the conformational changes of the DNA helical structure, such as forming irregular aggregate structures, induced by large quantities of molecular crowding media itself at this stage.

Jisuk Lee is currently a master degree student at the School of Chemistry and Biochemistry, Yeungnam University. Her current research interests focus on luminescence of lanthanide metal complexes.

Complexes of K[Eu1-xGdx(salen)2] (x=0-1.0) were synthesized and their structural and magneto-luminescent properties were investigated. The complex of K[Eu(salen)2] crystalized in the monoclinic P21/n space group. Exciting the Eu(III) complex with near-UV light resulted in sensitized red luminescence by the energy transfer from the ligand salen to the Eu(III) ion. For K[Eu1-xGdx(salen)2] in acetonitrile, the quantum yield of the sensitized luminescence (qsens) of x=0 was 49%. With increasing x, qsens increased and at x=0.9 qsens became the maximum (64 %). Above x=0.8, with increasing x, qsens decreased. The molar susceptibility of K[Eu1-xGdx(salen)2] were investigated as a function of x using a MPMS SQUID magnetometer. The evaluated Curie constant (C) satisfied the linear relation of C (emu K)=5.202.5x+2.6.

Ha Young Cho has completed her graduation in Chemistry and currently pursuing Master’s degree in Biophysical Chemistry from Yeungnam University, Republic of Korea.

Although the transition from the B-DNA to the A-form is essential for many biological concerns, properties of this transition have not been resolved yet. It is well known that DNA is in A-conformation during cell division. The B to A equilibrium can be analyzed conveniently due to significant changes of the Circular Dichroism (CD) and of the absorption spectrum. We have employed CD and Linear Dichroism (LD) methods to investigate the binding of water soluble meso-tetrakis (N-methyl pyridinium-4-yl) porphyrin (referred as TMPyP) and its derivatives, Co-TMPyP, with B- and A-calf-thymus DNA. When the physiological buffer was replaced by a water-ethanol mixture (~80 v/v%), B to A transitions occurred. Fluorescence emission spectra of TMPyP bound to DNA was shown different pattern under ethanol-water condition and water alone. The featureless broad emission bands of TMPyP are spilt in two peaks near at 658 and 715 nm in the presence of DNA under aqueous solution. In case of ethanol-water system, however, the emission bands are spilt in two peaks near at 648, 708 nm and 656, 715 nm with and without DNA, respectively. It may due to change of solution polarity. On the basis of obtained CD and LD data, TMPyP interacts with B-DNA by way of intercalation at low ratio under low ionic strength, 1 mM sodium phosphate. On the other hand, the interaction with A-DNA (80 v/v% ethanol-water system) occurs via non-intercalating manner. This difference may due to the reason from the structural property such as the groove of A-DNA is not as deep as in B-DNA and the bases are much more tilted. In the case of Co-TMPyP porphyrin preferably binds via outside self-stacking mode with B- and A-DNA.

Jung Hoon Lee has completed her PhD from University of Pittsburgh and Postdoctoral studies from Harvard School of Public Health. She is the Research Assistant Professor of Seoul National University College of Medicine. She has published more than 28 papers in reputed journals.

The Proteasome Core Particle (CP) is a 28 subunit cylindrical structure, the ends of which are formed by hetero-heptameric rings of alpha subunits. When in the closed form, the axial substrate translocation channel of the CP is topologically blocked by the convergent N-termini of α subunits. To probe the role of channel gating in mammalian proteasomes, we have deleted the N-terminal tail of alpha 3. The resulting alpha 3 delta N proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates. This is true of both free CP and of the 26S proteasome in the presence of ATPgammaS, representing the substrate-engaged state. Polyubiquitinated Sic1 also showed enhanced degradation by purified alpha-3 delta N proteasomes. Cells expressing the hyperactive proteasomes showed markedly elevated degradation of established proteasome substrates and multiplexed quantitative proteomics revealed ~200 proteins with reduced levels in the mutant cells. Nonetheless the mutants were viable and highly resistant to oxidative stress. Potentially toxic proteins such as tau exhibited reduced accumulation and aggregate formation. These data demonstrate that the CP gate is a key negative regulator of proteasome function in mammals and that opening the CP gate may be an effective strategy to increase proteasome activity and reduce levels of toxic proteins in cells.

Yuhlong Oliver Su has completed his PhD at The Ohio State University and worked as Research Associate at Princeton University. He is currently the Professor of Chemistry and President of National Chi Nan University. He has published more than 82 papers in reputed journals

In this study, the electrochemical behavior of zinc meso-substituted porphyrins in the presence of imidazole is examined by using both Cyclic Voltammetry (CV) and Density Functional Theory (DFT) methods. The results show that the first half-wave oxidation potentials (1st E1/2) of zinc porphyrins complexed with imidazole all move to negative side while the second ones (2nd E1/2) move positive side, resulting in larger half-wave oxidation potential splitting of the two oxidation states (ΔE=second E1/2 - first E1/2) comparing with the zinc porphyrins. By employing DFT calculations, we have found that both sterically controlled inter π-conjugation between porphyrin rings and meso-substituted phenyl groups and deformation of porphyrin rings do play important roles in contributing to the half-wave oxidation potentials. Imidazole exhibits strong effects the deformation of porphyrin rings which determine the 1st E1/2 while inter π-conjugation between porphyrin rings and mesosubstituted phenyl groups mainly contributes to the 2nd E1/2. Without imidazole, inter π-conjugation between porphyrin rings and meso-substituted phenyl groups is the only important criterion which effects both 1st E1/2 and 2nd E1/2 of zinc porphyrins.

Tai-Chia Chiu has recived his PhD degree in Chemistry from National Taiwan University, Taiwan, in 2003. He is currently working as a Professor of Applied Science at National Taitung University in 2016. He has published more than 40 papers in reputed journals. His current research inclue the development of analytical techniques for small molecules by capillary electrophoresis and green methods for synthesizing fluorescent carbon dot and its applications.

A simple strategy for the fabrication of a highly selective and sensitive dimethoate probe based on Rhodamine B (RB) functionalized gold nanoparticles (AuNPs) was developed. The quenching of fluorescence of RB occurs in the presence of AuNPs in the solution through the fluorescence resonance energy transfer (FRET) has been observed. In the presence of dimethoate, the FRET-based fluorescence of RB and AuNPs would be gradually recovered for the reason that dimethoate could displace RB molecules on the surface of AuNPs, leading to a significant increase in fluorescence intensity. The fluorescence was used for the detection of dimethoate concentration ranging from 0.005–1.0 ppm (R2 = 0.989) and recoveries of water and fruit samples were in the range of 101%–116%. This method have excellent selectivity and sensitivity for the detection of dimethoate in the presence of other pesticides. Owing to its high sensitivity, excellent selectivity and convenient procedure, this method will provide a promising alternative for dimethoate screening.

Teruyuki Tahara has received his Masters in Pharmaceutical Science from Kyoto University in 2005. Currently he is a Medicinal Chemist at Maruho Co. Ltd. His research interests are synthetic organic chemistry, medicinal chemistry and biological evaluation of synthetic molecules. From 2011 to 2015, he was a Visiting Scientist at Harvard University in the Laboratory of Professor Matthew Shair, conducting a joint research project with Maruho. He is currently a PhD student with Prof. Lida at Kinki University

Signal Transducer and Activator of Transcription 3 (STAT3) is a component of the JAK/STAT pathway. Therapeutic inhibition of STAT3 has been of high interest, as its aberrant activation has been linked to cancer, inflammation and other human diseases. The withanolide family natural product Withaferin A inhibits STAT3 activation. We designed, synthesized and evaluated simplified withanolide analogues SLW1 and SLW2 and found that SLW1 retained the STAT3 inhibitory activity of Withaferin A.

Sarah Y. Chang has her expertise in analytical chemistry. She developed new analytical methods for the determination of drugs in biological samples by capillary electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry.

A sensitive method for the determination of carbamazepine and clobazam using cyclodextrin-assisted dispersive liquid-liquid microextraction (CA-DLLME) coupled with capillary electrophoresis (CE) was developed. Cyclodextrin A and chloroform were used as the dispersive agent and extraction solvent, respectively. After the extraction, carbamazepine and clobazam were analyzed using CE with UV detection. The detection sensitivity was further enhanced through the use of sweeping technique. Under optimal extraction and stacking conditions, the calibration curves were linear over a concentration range of 2-40 ng/mL for carbamazepine and clobazam. The limits of detection (LODs) at a signal-to-noise ratio of 3 were 5 ng/mL and 6 ng/mL for carbamazepine and clobazam, respectively. An approximately 3757 to 4675-fold improvement in sensitivity was observed for the two analytes compared with the injection of a standard solution without the CA-DLLME and sweeping procedures. This developed method was successfully applied to the determination of carbamazepine and clobazam in human urine samples.

Ming Mu Hsieh has completed his PhDs degree in Chemistry from National Taiwan University, Taiwan in 2002. He is currently working as a Professor of National Kaohsiung University in 2012. He has published more than 40 papers in reputed journals. His current research inclue the development of pretreatmental (off-line) and analytical techniques for small molecules by capillary electrophoresis.

Dispersive liquid–liquid microextraction was combined with acetonitrile stacking in CE for the identification of three selective serotonin reuptake inhibitors (citalopram, fluoxetine, and fluvoxamine) in human fluids such as urine and plasma. Parameters that affect the extraction and stacking efficiency, such as the type and volume of the extraction and disperser solvent, extraction time, salt addition for Dispersive liquid–liquid microextraction, and sample matrices, pH, and concentration of the separation buffer for stacking, were investigated and optimized. Under optimum conditions, the enrichment factors were in the range of 1195–1441. Limits of detection ranged from 1.4 to 1.7 nM for the target analytes. Calibration graphs displayed satisfied linearity with R2 greater than or equal to 0.9978, and relative standard deviations of the peak area analysis were in the range of 2.9%–5.0% (n = 3). Recovery of all tricyclic antidepressant drugs from urine and plasma were in the range of 77%–117% and 79%–106%, respectively. The findings of this study show that Dispersive liquid–liquid microextraction-acetonitrile stacking-capillary electrophoresis is a rapid and convenient method for identifying tricyclic antidepressant drugs in urine and plasma.

Chia-Wei Chang has completed his Master degree in chemistry from National Tsing Hua University (NTHU) in 2014. He is the researcher of Industrial Technology Research Institute (ITRI) and National Metrology Laboratory (NML) in Taiwan. His responsibility is establishing and maintaining the system of humidity standards in order to connect the measurement traceability chain between international and domestic standards.

Amount of trace moisture in process gases supplied to semi-conductor industry is considered to be more and more crucial. To satisfy the demand for measurement of trace moisture, instrument companies have developed or manufactured a variety of analyzers. One of those analyzers which is based on cavity ring-down spectroscopy (CRDS) technique has been indicated with better performance due to its superior response time and stability from 10 nmol/mol (ppb) to 10 μmol/mol (ppm) of moisture in nitrogen gas. However, using gas cylinders as sources of trace moisture is not a proper way to evaluate the performance of analyzers, as substantial adsorption of water molecules on the inner surface of cylinder. Instead, this study established the dynamic trace-moisture generator which employs the diffusion method to produce stable concentration of water vapor once it reaches thermal equilibrium and adsorption-desorption equilibrium. With the dynamic trace-moisture generator, a commercial CRDS analyzer was under test on real-time and the results shows that the operating wavelength of laser might not be adjusted perfectly to the absorption band of water molecule. Therefore, the measurement stability of analyzer from direct reading could be improved by roughly a factor of 3, relative standard deviation from 1.96% to 0.64% at a level of 10 μmol/mol, through a tiny region spectrum scanning. This study demonstrates a feasible manner that generates trace moisture dynamically to evaluate the performance of commercial analyzer. It could be anticipated that a further improvement of measurement based on CRDS is to resolve the molecular absorption spectrum more precisely.

Worked in the departments of Specialty,Gas concertation analysis, dynamic gas concentration generation, the performance testing of gas analysis

Process gases, such as ammonia, carbon dioxide, dinitrogen monoxide and carbon tetrafluoride, are widely used in semiconductor processing. On line monitoring the particulate contamination of the delivered gases is important challenge. The technique of single particles inductively coupled plasma mass spectrometry (spICP-MS) was recently applied to particle analysis and numerous studies have established a set of metrological criteria of spICP-MS for sizing or quantifying various types of nanoparticles. In the technique, the the working gas of argon is chosen as the carrier gas. To prevent the plasma quenching, a gas exchange device (GED) was applied to remove the gas matrix. The gas converter consists of two concentric tubes in this study:a porous PTFE inner tube and a PFE outer tube. The aerosol sample flows in the inner tube and the clean argon gas flows in the outer tube. Because there is partial pressure difference on both sides of the inner tube, the carrier gas and the argon could penetrate the porous membrane and exchange. This research used Fourier transform infrared spectroscopy (FTIR) as gas concentration analyzer of inner and outer tube for optimized the dilution rate of gas exchange divece. We used GED to optimized four difference conponents such as NH3, CO2, N2O and CF4. Results show that CF4 compare with the other three components need largest outer tube flow rate. The permeabilities of the process gases were shown to be in order NH3 > CO2 > N2O > CF4. The order was in accordance with molecular weight of component.