Seminars 2011

Title:
Dye-sensitiized Solar Cells with Graphene Cathode
Speaker:Professor Ladislav Kavan
Date:14 December 2011  
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Martin Pumera
Abstract: 

Dye sensitized solar cell (DSC) also called Grätzel cell, represents an attractive alternative to solid state photovoltaics due to high efficiency, low cost and ease of fabrication. The generic device is a photoelectrochemical DSC. Its key components are dye-sensitized TiO2 photoanode, electrolyte solution with a redox mediator and the cathode material. The latter is typically a film of Pt nanoparticles on F-doped SnO2 (Pt-FTO) and the former is the I3-/I- in aprotic electrolyte medium. Graphene nanoplatelets (GNP) in the form of optically transparent thin films on FTO are useful as cathode material to replace platinum. They exhibit good electrocatalytic activity towards I3-/I-, particularly in electrolyte based on ionic liquids. Semitransparent (>85%) film of graphene nanoplatelets presented no barrier to drain photocurrents at 1 Sun illumination and potentials between 0 to ca. 0.3 V.

Recent progress in the field has been highlighted by replacing the traditional I3-/I- mediator by organic or organometalic couples with more positive redox potentials. The obvious motivation consists in enhancing the voltage of DSC. GNP exhibit high electrocatalytic activity for a mediator Co(L)2; where L is 6-(1H-pyrazol-1-yl)-2,2’-bipyridine. The exchange current densities for the Co2+/3+(L)2 redox reaction scaled linearly with the GNP film’s optical absorbance,  and they were by 1-2 orders of magnitude larger than those for the I3-/I- couple on the same electrode. The electrocatalytic activity of GNP films with optical transmission below 88% is outperforming the activity of Pt-FTO for the Co2+/3+(L)2 redox reaction.  Dye-sensitized solar cells achieved energy conversion efficiencies between 8 to 10 % for both GNP and Pt-based cathodes. However, the cell with GNP cathode is superior to that with Pt-FTO cathode particularly in fill factors and in the efficiency at higher illumination intensities.  In both cases, open circuit voltage exceeding 1 V is accessible, which represents a clear challenge for optimization of DSC. 

 

Title:
It Takes Alkynes to Make a World – From Organic Materials to Supramolecular Chemistry
Speaker:Professor Michael M Haley
Date:13 December 2011  
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Zhao Yanli
Abstract: 

This talk will present a contemporary description of all kinds of alkyne chemistry.  The first part of the lecture describes the Haley lab’s synthesis of dehydrobenzoannulenes, acetylene-linked aromatic macrocycles, and their use as functional pi-electron-rich materials with interesting optic and electronic properties.  By careful assembly of these molecules, the annulene properties can be tuned such that the molecules emit a rainbow of colors.  The second half of the lecture outlines a spin-off project involving alkyne-containing intermediates in the annulene syntheses.  By appending hydrogen-bonding motifs, we are developing a modular approach for the preparation of a family of highly-conjugated phenyl-acetylene receptors that provide concave binding pockets for anion recognition and anion-directed self-assembly.

 

Title:
Femtosecond Stimulated Raman Spectroscopy
Speaker:Professor Richard Mathies
Date:9 December 2011  
Time:4.30pm to 6.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Lee Soo Ying
Abstract: 

Femtosecond Stimulated Raman Spectroscopy or FSRS is a novel time-resolved vibrational technique that provides high-quality vibrational spectra on the femtosecond time scale of chemical reaction dynamics. The development and basics of the technique will be described.

Then the power of this method for revealing the structure of molecules undergoing chemical reactions will be exemplified by studies of the photochemical isomerization reaction that initiates vision in the pigment rhodopsin and that triggers photoswitching in azobenzene.

The structural changes that mediate electron transfer reactions are examined in a noncovalent donor: acceptor pi-complex. Finally, the nature of the reaction coordinate that controls proton transfer in the excited state of the green fluorescent protein is exposed.  FSRS provides a novel way to determine vibrational structural changes that occur on the time scale of chemical reaction dynamics.

 

 

Title:
Control of axial chirality by Suzuki and aryne coupling
Speaker:Professor Kwong Fuk-Yee
Date:8 December 2011  
Time:10.45am to 12.15pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract: 

Aryl nitriles are important structural motif in various pharmaceutical and natural products.  With the aid of Pd-CM-phos catalyst system, the first cyanation of aryl mesylate is achieved.  The reaction conditions are mildest reported so far for aryl chloride cyanation.  Moreover, the direct decarboxylative arylation of cyanoacetate is feasible for generating a,a-diaryl nitriles. 

References:

Yeung, P. Y.; Chung, K. H.; Kwong, F. Y.  Org. Lett. 2011, 13, 2912.

Yeung, P. Y.; So, C. M.; Lau, C. P.; Kwong, F. Y.  Org. Lett. 2011, 13, 648.

Yeung, P. Y.; So, C. M.; Lau, C. P.; Kwong, F. Y.  Angew. Chem. Int. Ed. 2010, 49, 8918.

 

Title:
Control of axial chirality by Suzuki and aryne coupling
Speaker:Professor Francoise Colobert
Date:7 December 2011  
Time:2.30pm to 4.00pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Shunsuke Chiba
Abstract: 

Chiral atropo-isomeric biaryl compounds have attracted great interest in the past decade for two fundamental reasons. First, it has been shown that there is an intimate relationship between the absolute configuration of the axial axis and the activity of a number of pharmacologically relevant biaryl molecules. Second, biaryls bearing axial chirality are one of the most important structural motifs within sucessful organometallic catalysts. In connection with a program devoted to asymmetric biaryl Suzuki coupling, we described a new atropo-diastereoselective Suzuki coupling reaction allowing the synthesis of biphenyl, binaphthyl and phenylnaphthyl derivatives with an excellent control of the axial chirality and excellent yields. A 1,3-chirality induction from a stereogenic carbinol to the chiral axis is mainly responsible for the atropo-diastereoselectivity. This methodology provides an efficient catalytic access to axially chiral biaryls bearing a benzylic stereocenter such as (–)-steganacin, korupensamine A and vancomycine biaryl unit.         

We also reported an efficient route to a new family of axially chiral biaryl ligands by a Suzuki-Miyaura cross-coupling reaction between ortho,ortho′-disubstituted aryl iodides bearing in ortho position a tert-butyl or p-tolylsulfinyl group and ortho-substituted phenyl or naphtyl boronic acids or esters. The comparison between the t-BuSO and p-TolSO groups as chiral controllers is studied. The modularity of the approach is demonstrated by the preparation of a variety of enantiopure axially chiral mixed S/N and S/P ligands.

Starting from racemic biaryl we recently developed the atropodiastereoselective resolution using as chiral auxiliary the enantiopure sulfoxide giving after sulfoxide lithium exchange an atropoenantiopure mono di or trihalogenated biaryls which appeared as very promising building block and turned out to be suitable toolbox for the synthesis of several biphenyls with complete control of axial chirality.

 

Title:
Carbenes, Carbones and Group-13 and Group-15 Homologues
Speaker:Professor Gernot Frenking
Date:7 December 2011  
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Francois Mathey
Abstract: 

The topic of the lecture are theoretical studies of divalent carbon(0) compounds which have the general formula CL 2  where L is a σ electron donor. The chemical bond between the ligand L and carbon is a L→C donor-acceptor bond which means that the carbon atom in CL2  carries two electron lone pairs. Experimentally known examples where L = PR3  are carbodiphosphoranes (CDP)1 which have already been   synthesized in 19632 . The donor-acceptor model L→C←L nicely explains widening of the bonding angle when L becomes a better π-acceptor: 

A theoretically predicted new class of divalent carbon(0) compounds are carbodicarbenes C(NHC)2 (1) where NHC = N-heterocyclic carbene3  which have become synthesized in the meantime. 4The latter compounds are related to tetraaminoallenes 2 (R = NX2 )5 . The calculations  predict that divalent carbon(0) compounds have promising chemical  properties particularly as ligands in  transition  metal  complexes  which  should  be  investigated  with experimental methods. We also report about heavier group-14 species EL2  (E = Si – Pb)6 and group-15 homologues (N+ )L2.7Very recently, the group-13 homologue (BH)(CAAC)2 where CAAC is a cyclic (alkyl)(amino)carbene has become synthesized.8

1.Öxler, B. Neumüller, W. Petz, G. Frenking,  Angew. Chem. Int. Ed. 2006, 45, 8038. 2. F. Ramirez, N.B. Desai, B. Hansen, N. McKelvie, J. Am. Chem. Soc. 1961, 83, 3539. 3.   R. Tonner, G. Frenking,  Angew. Chem. Int. Ed. 2007, 46, 8695. 4 C.A.  Dyker,  V. Lavallo,  B.  Donnadieu,  G. Bertrand, Angew. Chem. Int.Ed. 2008, 47, 3206. 5. R. Tonner, G. Frenking, Chem. Eur. J. 2008, 14, 3260, 3273. 6. N. Takagi, T.  Shimizu, G.  Frenking,  Chem. Eur. J. 2009, 15, 3448, 8593. 7. R. Sure, S. Klein, G. Frenking, Chem. Eur. J., submitted for publ. 8. R. Kinjo, B. Donnadieu, M. A. Celik, G. Frenking, G. Bertrand, Science, 2011, 333, 610.   

 

Title:
Tuning the activity of platinum(IV) complexes as anticancer prodrugs
Speaker:Dr Ang Wee Han
Date:5 December 2011  
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Xing Bengang
Abstract: 

Platinum-based anticancer drugs, cisplatin, carboplatin and oxaliplatin, are some of the most effective chemotherapies used in clinic (Figure). Their cytotoxic activity against cancer stems from a combination of processes including cell entry, drug activation, DNA binding and transcription inhibition, resulting in apoptotic cell death. Due to limitations in platinum-based therapy arising from toxicity and side-effects, there have been a resurgence in interest in studying diammine-platinum(IV) complexes as anticancer prodrugs, with satraplatin currently undergoing clinical trials (Figure). Solvation of labile chloride ligands is suppressed in the stable diammine-platinum(IV) scaffold mitigating the effects of poor selectivities due to rapid aquation of diammine-platinum(II) complexes, such as cisplatin. We are particularly interested in a class of platinum(IV) complexes containing hydrophobic benzoate ligands which displayed improved cytotoxicites in vitro (Figure). By altering the nature and composition of these ligands, we aim to tune the properties of this class of complexes and enhance their therapeutic potential. We will also report a novel method of delivering these complexes via simple hydrophobic entrapment.

 

Title:
Phosphorus Cations as Synthetic Targets – From Fundamentals to Application
Speaker:Dr Jan J. Weigand
Date:1 December 2011  
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Francois Mathey
Abstract: 

Our research focuses on the development of phosphenium cations with promising reactivity, phosphorus rich [P] building blocks with high synthetic potential and cationic polyphosphorus cages.

The particular interest in the functionalization of white phosphorus stems from the demand of new phosphorus-containing structures and the direct synthesis of organophosphorus compounds (OPCs). Substantial efforts have been devoted to the development of direct P4 functionalization to escape the traditional stages via the intermediacy of PCl3 and subsequent transformation reactions. In this respect we are developing general protocols for the formation of cationic phosphorus cages by consecutive insertion of phoshenium cations into P-P bonds of P4.[1,2] We could show, that these cationic cages undergo stepwise degradation reaction with NHCs to form novel [P] building blocks. Furthermore, we are interested in efficient, large scale synthesis of highly-charged phosphorus-centered cations. The unique combination of weakly bound pyrazole moieties and the high positive charge in e.g. the Janus-head type diphosphorus trication [pyr3P2][OTf]3 (pyr = 3,5-dimethylpyrazole) results in an high synthetic potential. The application of such highly-reactive, polycationic phosphorus compounds aims for the generation of novel OPCs.[3] This is an conceptually new approach to the preparation of large phosphorus and mixed phosphorus-main group element frameworks.[4]

[1] Weigand, J. J.; Burford, N.; Decken, A. Eur. J. Inorg. Chem. 2008, 4343; [2] a) Weigand, J. J.; Holthausen, M.; Fröhlich, R. Angew. Chem. Int. Ed.  2009, 48, 295; b) Holthausen, M. H.; Weigand, J. J. J. Am. Chem. Soc., 2009, 131, 14210; c) Holthausen, M. H.; Richter, C.; Hepp, A.; Weigand, J. J. Chem. Commun 2010, 46, 6921; [3] Feldmann, K.-O.; Schulz, S.; Klotter, F.; Weigand, J. J. ChemSusChem 2011, in press; [4] a) Weigand, J. J.; Feldmann, K.-O.; Echterhoff, A. K. C.; Ehlers, A.; Lammertsma, K. Angew. Chem. Int. Ed.  2010, 49, 6178; c) Weigand, J. J.; Feldmann, K.-O.; Henne, F. D. J. Am. Chem. Soc.  2010, 132, 16321.

 

Title:
Conjugated Polymer as a New Platform for Sensing and Imaging Applications
Speaker:Dr Liu Bin
Date:30 November 2011 
Time:4.00pm to 5.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Xing Bengang
Abstract: 

There is an increasing trend of using light-harvesting conjugated polymers as active materials for sensing and imaging applications. In this talk, I will discuss different strategies of using conjugated polymers as signal reporters or signal amplifiers for chemical and biological sensing. In addition, our recent progress in conjugated polymer based imaging will also be discussed. At last, I will briefly introduce organic nanoparticles with aggregation induced emission features as replacement for quantum dots in sensing and imaging applications. 

 

Title:
Geminal Disubstitution and Olefination of Imines
Speaker:Professor Shi-Kai Tian
Date:29 November 2011 
Time:10.45am to 12.15pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng 
Abstract: 

Our research focuses on the development of new synthetic methods based on the transformations of nitrogen-containing compounds, particularly those with carbon-nitrogen bond cleavage. We have recently developed the geminal disubstitution of imines with various nucleophiles and the olefination of imines with phosphorus- or sulfur-stabilized carbon nucleophiles. In these reactions the substituents on the imine nitrogen atoms have been successfully utilized to tune the reactivity and stereoselectivity.

 

Title:
Metal-Organic Frameworks and Metal-Organic Polyhedra: Preparation and Application
Speaker:Professor Zhou Hong-Cai
Date:23 November 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Xing Bengang
Abstract: 

The combination of bridging organic linkers and metals or metal clusters through coordination bonds leads to a metal-organic polygon or polyhedron (MOP), if the structure converges, or metal-organic framework (MOF), if it does not. The inherent porosity of MOPs and MOFs can be exploited to store or capture various gases including hydrogen, methane, and carbon dioxide.  This presentation will cover a wide range of topics including MOPs showing intriguing gas-adsorption selectivity, MOFs with exceptionally high gas uptake, and the inter-conversion of MOPs and MOFs.

 

Title:
Development of New Materials Powered by Organic Synthesis
Speaker:Professor Shigeru Yamago
Date:22 November 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Chen Hongyu
Abstract: 

Design and synthesis of new organic molecules are the heart of synthetic organic chemistry. Such new molecules would become key reagents and materials for future science and technologies. Our group has been especially focusing on the synthesis of new organic molecules for controlling radical polymerization and becoming as electronic as well as optoelectronic materials. In this seminar, I am going to present the most recent advancement of such two topics.

The first topic is the development of new controlling reagents for living radical polymerization. We have already developed several organotellurium, organostibine, and organobismuthine compounds (representative chemical structures are shown below) are excellent controlling agents for radical polymerization. New conditions for the precision control of the living radical polymerization and its application in macromolecular engineering will be presented.1)

The second topic is the synthesis of cycloparaphenylenes. Due to their unique structures with distorted p orbitals, CPPs have attracted the attention of theoretical and synthetic chemists more than half a century. Since cycloparaphenylenes are simplest structural constituent of armchair carbon nanotube, they would become a seed for the synthesis of structurally uniform carbon nanotubes. A new synthetic strategy for cycloparapnenylens (see below) and their physical properties will be presented.2)

References

1) Yamago, S. Chem. Rev. 2009, 109, 5051, Mishima, E.; Yamada, T.; Watanabe, H.; Yamago, S. Chem. Asian J. 2011, 6, 445, Kayanara, E.; Yamada, H.; Yamago, S. Chem. Eur. J. 2011, 17, 5272, Mishima, E.; Yamago, S. Macromol. Rapid Commun. 2011, 32, 893.

2) Yamago, S.; Watanabe, Y.; Iwamoto, T. Angew. Chem. Int. Ed. 2010, 49, 757-759, Iwamoto, T.; Watanabe, Y.; Sakamoto, Y.; Suzuki, T.; Yamago, S. J. Am. Chem. Soc. 2011, 133, 8354, Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S. Angew. Chem. Int. Ed. 2011, 50, 8342.          

 

Title:
Preparation of optically active aza-Morita-Baylis-Hillman adducts and their use of heterocyclic synthesis
Speaker:Professor Akio Kamimura
Date:17 November  2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Kim Sunggak
Abstract: 

Aza-Morita-Baylis-Hillman reaction (aza-MBH reaction) is one of the most potentially useful reactions in organic synthesis. Recently we examined the asymmetric modification of  the reaction, and successfully developed asymmetric Aza-Morita-Baylis-Hillman equivalent  reaction, in which enolate intermediates were generated by a nucleophilic attack of thiolateanion. 1)  In this presentation we will show details of the reaction and its application for heterocyclic synthesis via RCM reaction or the Pauson-Khand reaction. 2)  A novel boomerang-type radical cyclization will be discussed. 3) 

1) Kamimura, A.; Okawa, H.; Morisaki, Y.; Ishikawa, S.; Uno, H. J. Org. Chem. 2007, 72, 3569.  2) Ishikawa, S.; Noguchi, F.; Kamimura, A. J. Org. Chem. 2010, 75, 3578; Ishikawa, S. Noguchi, F.; Kamimura, A. Tetrahedron Lett. 2010, 51, 2329. 3) Kamimura, A.; Ishikawa, S.; Noguchi, F.; Murafuji, T.; Uno, H. submitted  

 

Title:
New Dimension of Acid and Base Catalysis
Speaker:Professor Shu Kobayashi
Date:16 November  2011 
Time:2.30pm to 4.00pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Koichi Narasaka
Abstract: 

(1) Catalytic Carbanion Reaction; Carbanion formation using a catalytic amount of base; Catalytic Silicon Chemistry

(2) Alkaline Earth Metal Catalysts; Ca-Catalyzed Asymmetric Michael Reactions, [3+2]Cycloaddition

(3) Silver Amide-Catalyzed [3+2]Cycloaddition

(4) Fluorenone Imines for C-C Bond Formation

 

Title:
Sub-10-nm Plasmonics
Speaker:Dr Joel Yang Kwang Wei 
Date:16 November  2011 
Time:11.00am to 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Ling Xing Yi
Abstract: 

On metallic nanostructures, plasmons exist in the form of resonant charge oscillations. With metal nanostructures placed close together, plasmon resonances lead to strong electric fields localized in the gap region. These resonances are highly dependent on the size of the gaps. For instance smaller gaps (sub-10-nm) are expected to yield more intense fields and larger energy splits between the “bonding” and “anti-bonding” plasmon modes than large gaps. These plasmonic nanostructures find use in coupling light in and out of molecular materials, e.g. in high sensitivity molecular spectroscopy with surface-enhanced Raman scattering (SERS). In this talk we will discuss the fabrication of plasmonic nanostructures with gaps as small as 0.5 nm. We will discuss also the electron energy-loss spectroscopy (EELS) method used in testing the plasmonic responses of these structures by locally and electrically exciting the plasmons.

 

Title:
Isotope effect as a new weapon against oxidative stress
Speaker:Dr Mikhail Shchepinov
Date:11 November  2011 
Time:11.00am to 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Dragoslav Vidovic
Abstract: 

A method will be discussed that has the potential to increase the stability of lipids, proteins, nucleic acids and other cellular components towards the detrimental damages caused by reactive oxygen species (ROS). The rate-limiting step of most ROS-driven oxidation reactions is hydrogen abstraction. The oxidation-susceptible sites within these (bio)molecules can thus be made less vulnerable to ROS-driven oxidation by incorporating heavy stable isotopes, such as deuterium or/and carbon-13. Ingestion of isotopically reinforced building blocks, such as amino acids, lipids, and components of nucleic acids and their subsequent incorporation into macromolecules would make the latter more stable to ROS courtesy of the isotope effect. The suggested approach may lead to enhanced resistance toward oxidative stress.

 

Title:
Biocompatible Nanoparticles as Cancer Imaging Probes and Drug/Gene Delivery Vehicles
Speaker:Professor Shawn Chen
Date:3 November  2011 
Time:3.00pm to 4.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Xing Bengang 
Abstract: 

Nanomedicine, which is the medical application of nanotechnology, ranges from the medical applications of nanomaterials, to nanoelectronic biosensors, and even possible applications of molecular nanotechnology. This talk will focus on three major aspects: (1) the development of unique composite nanoparticle platforms with unique physical and chemical properties and suitable labeling for multimodality of imaging the functional and molecular properties of cancer; (2) the design of nanomaterials that have both passive targeting and specific targeting characteristics and capacity to load chemo and gene therapeutics for cancer treatment; and (3) theranostics nanoparticles that have both imaging and therapy components to pinpoint the fates of both the delivery vehicle and cargo, as well as the treatment efficacy. This talk will also briefly touch base on the limitations and future challenges of nanoparticle-based systems.

 

Title:
Bioorganometallic Chemistry: Synthesis, Structures, Molecular Recognition, Biocatalysis Studies, and Organometallic Pharmaceuticals
Speaker:Dr Richard H Fish
Date:21 October 2011 
Time:1100am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Leong Weng Kee
Abstract: 

Reactions of [Cp*Rh(H2O)3](OTf)2 with a variety DNA bases provided a number of new structures as a function of pH that were unequivocally characterized via single crystal x-ray crystallography. Several of these unique Cp*Rh-nucleobase structures were found to be receptors; for example, 1, in molecular recognition studies via non-covalent processes, such as π-π, hydrophobic, and selective H-bonding interactions, with guests, such as drugs, proteins, and other important biological molecules; host 1-guest 2 (L-tryptophan).1

The chiral synthesis of alcohols from their prochiral ketones, via two novel catalysis approaches, will also be presented, including a co-factor regeneration procedure with insitu generated [Cp*Rh(bpy)H]+ and NAD+ models, 1-benzylnicotinamide triflate, 3, and b-nicotinamide-5'-ribose methyl phosphate, 4.  Importantly, the 1,4-dihydro analogs of  3 and 4 are indeed recognized by the enzymes, HLADH, Cytochrome P450, BM3, and a Catecholase, at their binding sites for catalyzed, highly enantioselective synthesis, and biooxidation reactions; a new paradigm for biocatalysis.

Organometallic pharmaceuticals represent a new discipline for drug discovery.  The reactions of Cp*Rh(solvent)3](OTf)­­2 complexes with hydroxytamoxifen derivatives provided an unprecedented N-π rearrangement to provide complex 5, which was found to competitively bind at the estrogen receptor, and was found to be a growth inhibitor with several breast cancer cell lines.  Finally, the reactions of G-protein controlled receptor peptides   with [Cp*Rh(H2O)3](OTf)2, as a function of pH, and tyrosine selective, will also be discussed.            

 

Title:
NS2B/3 Serine Protease Inhibitors: Discovery and Design
Speaker:Professor Rahman Noorsaadah
Date:14 October 2011 
Time:10.45am to 12.15pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract: 

The search of an anti-viral for dengue virus infection has been focused on the different phases of the viral lifecycle (virus attachment, viral entry, trafficking, translation or replication). Despite its morbidity and mortality, only few antiviral therapies have been tested and little is known about the effects and mechanisms of the anti-viral agents. 

Studies have shown the NS2B/NS3 component of the protease to be involved in the virus replication process by activating the cleavage in the non-structural region of the viral polyprotein at NS2A/NS2B, NS2B/NS3, NS3/NS4A and NS4B/NS5 junctions (Arias et al., 1993; Teo et al., 1997; Yusof et al., 2000).  Bioassay-guided screening of some natural product extracts gave some hits that are able to inhibit the activity of NS2B/3 DEN2 serine protease, both competitively and non-competitively.  Based on these hits, docking studies were carried out and a compound was designed to mimic the interactions observed between the protease and the natural ligand.  A synthesis of this designed ligand was then carried out. Biological screening of this compound and some of its intermediates gave some positive indications as to the potential of this “new” class of compounds as anti-viral agents for the NS2B/3 DEN2 serine protease.

 

Title:
Structural Study-Guided Development of Novel and Practical Chiral Catalysts 
Speaker:Professor Deng Li
Date:12 October 2011 
Time:2.30pm to 4.00pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Shunsuke Chiba

 

Title:
Ring Transformations of Functionalized β-Lactams
Speaker:Professor Norbert De Kimpe
Date:7 October 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Roderick Bates
Abstract: 

β-Lactams are known for their antibiotic properties but are also known for their potential as building block in synthetic organic chemistry. β-Lactams, substituted with halogens in the side chain at the 4-position, have almost not been studied. The synthetic potential of these specifically halogenated β-lactams will be highlighted by the synthesis of g-lactams, bicyclic β-lactams, aziridines, azetidines, pyrrolidines, perhydroazepines and piperidines. These halogenated azetidinones are, among others, suitable for ring transformations via iminium intermediates to afford a whole variety of functionalized g-lactams, carrying halogens, alkoxy, hydroxy and nitrogen functionalities. The intermediate charged species were intercepted by intramolecular trapping with internal nucleophiles to generate novel bicyclic g-lactams. This peculiar type of rearrangement was supported by molecular modeling. Further efforts were undertaken to prove the suggested mechanism. The title functionalized b-lactams were suitable substrates for the synthesis of bicyclic b-lactams of the rare 2-oxa-6-azabicyclo[3.2.0]heptan-7-one type, which are known for their antimycotic activities.

The ring expansion of halogenated β-lactams towards funtionalized piperidines concerned the first example of the transient generation of the strained 1-azoniabicyclo[2.2.0]hexanes which stereospecifically underwent ring opening to the final 6-membered azaheterocycles.

These ring expansions allowed the design of suitable, flexible and versatile building blocks for a large variety of azaheterocyclic compounds.

 

Title:
Ring Transformations of Functionalized β-Lactams
Speaker:Professor Norbert De Kimpe
Date:7 October 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Roderick Bates
Abstract: 

β-Lactams are known for their antibiotic properties but are also known for their potential as building block in synthetic organic chemistry. β-Lactams, substituted with halogens in the side chain at the 4-position, have almost not been studied. The synthetic potential of these specifically halogenated β-lactams will be highlighted by the synthesis of g-lactams, bicyclic β-lactams, aziridines, azetidines, pyrrolidines, perhydroazepines and piperidines. These halogenated azetidinones are, among others, suitable for ring transformations via iminium intermediates to afford a whole variety of functionalized g-lactams, carrying halogens, alkoxy, hydroxy and nitrogen functionalities. The intermediate charged species were intercepted by intramolecular trapping with internal nucleophiles to generate novel bicyclic g-lactams. This peculiar type of rearrangement was supported by molecular modeling. Further efforts were undertaken to prove the suggested mechanism. The title functionalized b-lactams were suitable substrates for the synthesis of bicyclic b-lactams of the rare 2-oxa-6-azabicyclo[3.2.0]heptan-7-one type, which are known for their antimycotic activities.

The ring expansion of halogenated β-lactams towards funtionalized piperidines concerned the first example of the transient generation of the strained 1-azoniabicyclo[2.2.0]hexanes which stereospecifically underwent ring opening to the final 6-membered azaheterocycles.

These ring expansions allowed the design of suitable, flexible and versatile building blocks for a large variety of azaheterocyclic compounds.

 

Title:
Asymmetric Reactions with Cooperative And Multifunctional Catalysis 
Speaker:Professor Deng Li
Date:7 October 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS Lecture Theatre 3 
Host:Professor Leung Pak Hing

 

Title:
Structure and fragment based design of small molecule chemical probes of protein interfaces that read posttranslational modifications
Speaker:Dr Alessio Ciulli
Date:27 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Chen Hongyu 
Abstract:

Targeting protein-protein interfaces using small molecules holds great potential for elucidating complex cellular pathways, for target validation in drug discovery and ultimately developing the next generation of molecular therapeutics. Many functional protein-protein interactions are dictated by the post-translational modification (PTM) of specific amino acids of one or both of the partner protein, thereby expanding Nature’s inventory of recognition patterns and regulatory control mechanisms. In my talk I will illustrate two structure-based studies of targeting protein interfaces that selectively read PTMs of amino acids on partner proteins. Firstly, I will describe the discovery of novel drug-like small molecules that target the interface between the von Hippel Lindau protein (pVHL), which functions as part of a multi-subunit E3 Ubiquitin Ligase complex, and the alpha subunit of the Hypoxia Inducible Factor (HIF-a). This protein-protein interaction, which is driven by hydroxylation of a proline residue in HIF-a, is responsible for targeted polyubiquitination and proteasome-dependent degradation of HIF-a, a crucial regulatory mechanism in oxygen sensing. Disruption of this interaction in cells is expected to mimic the hypoxic response and is a potential target for the treatment of chronic anemia and acute ischemia. Secondly, I will discuss progress towards fragment-based design of chemical probes of bromodomains, a family of epigenetic readers of lysine acetylation in histones and other proteins. These studies aim to provide new tools to interrogate druggability and probe selectivity within the bromodomain family, to elucidate the biological role of individual bromodomains within the human proteome, and ultimately to validate them as drug targets against disease. 

 

Title:
Optical Properties of Noble Metal Nanocrystals
Speaker:Mr Lee Yih Hong
Date:23 September 2011 
Time:2.00pm to 3.00pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Ling Xing Yi
Abstract:

The localized surface plasmons of noble metal nanocrystals give rise to a wide array of intriguing optical properties among these materials. Consequently, the field of plasmonics has become one of the most hotly researched areas in recent years, spurred by the multitude of potential applications that could be developed using noble metal nanocrystals. Currently, these materials have found important uses in the general areas of (bio)chemical sensing, information storage, catalysis, biomedical science and electronic devices. The optical properties and dynamics of noble metal nanocrystals will be discussed in this presentation. A brief overview on the optical properties of noble metal nanocrystals is first given together with some discussion on recent works in this area. This is followed by a comparison on the refractive index sensitivity and photoluminescence properties between Au and Ag nanocrystals. Nanocrystals of similar sizes and extinction peak positions were prepared. Ag nanocrystals were found to be more sensitive to refractive index changes than Au due to its larger dielectric function. A larger local field enhancement around Ag nanocrystals also led to more efficient emission than the Au counterparts. A size-dependent investigation of the emission properties of Au nanooctahedra indicates that smaller Au nanooctahedra have higher quantum yields due to larger local field enhancement factors. Emission arising from both radiative interband recombination and radiative plasmon decay were also observed from Au nanooctahedra. The nonlinear optical switching behaviors of Au nanocubes and nanooctahedra are also discussed. Both saturable absorption (SA) and reverse SA were measured at low and high excitation intensities respectively. SA was brought about by ground-state plasmon band bleaching at low fluences. Nonlinear processes such as scattering and absorption were responsible for the observed RSA at high excitation intensities.           

 

Title:
Challenges in Modeling Water: from Clusters, Interfaces to Bulk
Speaker:Dr Kuo Jer-Lai
Date:12 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Liu Xuewei 
Abstract:

Water is one of the most important substances of life, but the detailed structure and dynamical properties at interfaces is far from well understood. Many fundamental questions in biology, chemistry and physics are directly related to the chemical and physical properties of interfacial water. For examples, it was noted that water’s interactions with proteins play an essential role in determining the folding mechanism and the functions of the protein. The solvation of various atmospherically important chemicals at water/air interface dictates the reactivity of aerosols, which are known to affect not only short-term air pollution but also long-term climate changes. Furthermore, effects of water on the electrochemical reaction on semi-conductor and metal surfaces are larger unknown which hinder the efficiency of converting solar energy for water splitting – an important and critical issue in energy research. One of the common themes for the above-mentioned subjects is the rough energy landscape of aqueous systems that hinder a straightforward way for a structural determination from first-principle methods.

Our recent effort in developing a first-principle based multi-model methods is to integrate the efficiency of empirical models and the accuracy of first-principle methods to study various aqueous systems ranging from large-sized water clusters, water interfaces, to various condensed phases (low temperature amorphous phases and proton ordering process). For clusters, we can benchmark the commonly used DFT methods against other high-level quantum chemistry methods and in condensed phases, we also seek for comparisons with quantum Monte Carlo methods. In this talk, we will discuss some of the successes and failures we have encounter and how we utilize the information learnt to move toward a consistent picture in simulating aqueous systems.

 

Title:
Syntheses of O- and S-linked Oligo-sialic Acids
Speaker:Professor Chun-Cheng Lin
Date:9 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Liu Xuewei 
Abstract:

Sialic acid is the most common non-reducing sugar in glycoproteins and glycolipids. There, they act either as masks or recognition sites for the ligand-receptor and cell-cell recognition in many important biological events. However, the synthesis of sialo-conjugates, especially oligo-sialic acid, is one of the most challenging tasks in carbohydrate chemistry due to the difficulty to control the formation of the α-glycosidic bond during the coupling step with sialic acid. Recently, we developed an efficient stereoselective synthesis of α-(2®9)-tetrasialic acid by using a tri-O-chloroacetyl-derivatized sialyl donor and a triol sialyl acceptor. Both the acceptor and the donor were also protected with a cyclic 5-N-4-O-carbonyl protecting group. The donor is highly reactive, and enabled α-selective sialylation with various primary, secondary and tertiary acceptors under in situ activation conditions (NIS/TfOH, -78 °C, acetonitrile/dichloromethane). The trans-fused oxazolidinone ring and O-chloroacetyl protecting groups were easily removed under mild reaction conditions to provide the fully deprotected α(2®9)-tetrasialic acid.

A new approach to the synthesis of S-linked α(2®9)-oligo-sialic acids was also developed using an asymmetric tert-butyl disulfide linkage as an anomeric thiol protecting group. Compared with conventional thiosialosides, the asymmetric disulfide sialosides can tolerate conditions under which functional groups are modified without producing the undesired elimination and racemization products. In addition, the asymmetric tert-butyl disulfide protection group can be efficiently deprotected to afford a thiol nucleophile at the α anomeric position without flipping the anomeric stereochemistry. By this strategy, the syntheses of tetra-, hexa-, and octa-α(2,9) sialic acids, tri-α(2,8) sialic acid, and α(2,8)/α(2,9) tri-sialic acid were achieved.

 

Title:
Chemistry-based protein modification in test tube and in live cell
Speaker:Professor Itaru Hamachi
Date:7 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Brendan Orner
Abstract:

Specific protein labeling and imaging may have a significant potential in fundamental research of chemical biology and also in medical diagnosis.  Here I describe our recent results on the development of chemistry-based methods for specific labeling and imaging of protein surface driven by selective protein recognition and reaction.  A phenylsulfonate derivative (Tosyl) that tethers a ligand part for selective binding to a target protein and a probe part to be attached to the protein surface was designed and synthesized.  The probe was incubated with a protein in cell lysate, as well as in a pure sample, to carry out the protein selective and site selective labeling.  More remarkably, this chemistry was demonstrated to be applicable to selective labeling of endogenous proteins inside live cells.  Detailed investigation of the reaction mechanism clarified that self-assembly of the probe with nano-meter size is important for protein labeling and off-on type of imaging of a target protein.

 

Title:
Chemical and Biological Diversity: New Approaches to Synthesising Bioactive Small Molecules
Speaker:Professor Adam Nelson
Date:7 September 2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Xing Bengang 
Abstract:

The presentation will focus on two complementary approaches for the synthesis of biologically active molecules. 

First, the application of directed evolution in the generation of synthetically useful aldolase catalysts will be described.1  We have used this approach, which we have undertaken in collaboration with Professor Alan Berry, to generate enzymes with expanded substrate selectivity and tailored stereochemical properties.  In particular, the creation of a pair of stereochemically complementary enzymes will be described.  The enzymes have been exploited in the diastereoselective synthesis of sialic acid mimetics.

Second, a robust approach to the synthesis of natural product-like molecules will be presented.2  Methods which allow the systematic variation of ligand scaffold are particularly rare, and the scaffold diversity of chemical libraries does not approach that of natural products. The presentation will describe a synthetic approach which yields natural product-like molecules of unprecedented skeletal diversity.

References:

1) (a) A. Berry, S. Domann, A. Nelson and G. Williams, Proc. Natl. Acad. Sci. USA 2003, 100, 3143; (b) T. Woodhall, G. Williams, A. Berry and A. Nelson, Angew. Chem., Int. Ed., 2005, 44, 2109; (c) G. J. Williams, T. Woodhall, L. Farnsworth, A. Nelson and A. Berry, J. Am. Chem. Soc. 2006, 128, 16238; (d) A. Berry, A. Nelson and G. J. Williams, Cell. Mol. Life Sci. 2004, 61, 3034; (e) T. Woodhall, G. Williams, A. Berry and A. Nelson, Org. Biomol. Chem. 2005, 3, 1795-1800; (f) G. J. Williams, T. Woodhall, A. Nelson and A. Berry, Prot. Eng. Des. Sel. 2005, 18, 239; (g) A. Bolt, A. Berry and A. Nelson, Arch. Biochem. Biophys. 2008, 474, 318; (h) I. Campeotto, A. H. Bolt, T. A. Harman, C. Dennis, C. H. Trinh, S. E. V. Phillips, A. Nelson, A. R. Pearson and A. Berry, J. Mol. Biol. 2010, in press.

2) (a) S. Leach, C. Cordier, D. Morton, G. McKiernan, S. Warriner and A. Nelson, J. Org. Chem. 2008, 73, 2752; (b) C. Cordier, D. Morton, S. Murrison, A. Nelson and C. O’Leary-Steele, Nat. Prod. Rep. 2008, 719; (c) C. Cordier, D. Morton, S. Leach, T. Woodhall, C. O’Leary-Steele, S. Warriner and A. Nelson, Org. Biomol. Chem. 2008, 6, 1734; (d) D. Morton, S. Leach, C. Cordier, S. Warriner and A. Nelson, Angew. Chem. Int. Ed. 2009, 48, 104 (VIP article); C. O’Leary-Steele, C. Cordier, J. Hayes, S. Warriner and A. Nelson, Org. Lett. 2009, 11, 915-918; C. O’Leary-Steele, P. J. Pedersen, T. James, T. Lanyon-Hogg, S. Leach, J. Hayes and A. Nelson, Chem. Eur. J. 2010, 16, 9563-9671 S. Murrison, S. K. Mauyra, C. Einzinger, B. McKeever-Abbas, S. Warriner and A. Nelson, Eur. J. Org. Chem. 2011, in press.

 

Title:
New Reactions and the Secrets of their Success
Speaker:Professor Jeffrey Bode
Date:6 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Robin Chi 
Abstract:

Over the past several years our group has engaged in a program of reaction discovery that has led to the development of new organic reactions. Of particular interest has been the development of amide bond forming reaction including both novel chemoselective ligation strategies suitable for peptide synthesis and bioconjugation as well as catalytic reactions for waste free amidation. The principles behind the catalytic amidation reactions have also been applied to a new generation of highly enantioselective carbon–carbon bond formation.

This talk will cover our latest developments in enantioselective catalysis, chemoselective amide formation, and mechanistic studies. These efforts have recently led to the first general method for the catalytic, enantioselective resolution of chiral secondary amines with outstanding selectivity.

 

Title:
Behind the curtains : A snapshot of our research activities in DSO 
Speaker:Dr Tan Boon Huan
Date:1 September 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Xing Bengang 
Abstract:

Often, the research activities in DSO are shrouded in clouds of secrecy. Today, it is my pleasure to provide an overview of the different types of research activities that members of the Detection and Diagnostics Laboratory are engaged in.

The main mission of the laboratory is to provide 24/7 support to the Singapore Military in terms of microbial diagnostics during crisis moments. Take for example, our involvement in the SARS crisis, and the recent pandemic influenza infections.

Another mission is to continue to develop better assays for a wide range of microbes – be it virus, bacteria, fungi, or parasites; and from different clinical and environmental matrices. Here I will illustrate with examples of specific case studies where to assist in the confirmation of various etiological agents causing infectious diseases. In the past, we have developed single diagnostic assays, and now our focus is broad-based methods where we use a single tube to detect for the presence of multiple microbes. We are always on the lookout for the latest cutting edge methods to improve the sensitivity of our diagnostic assays. Or new methods to assess which will better our existing assays.

We usually work in partnership with a wide range of collaborators at the national, regional and international levels, ranging from the academic sectors (universities and polytechnics) to civilian sectors.

Most of the data have been published in international journals and presented in international meetings. 

 

 

Title:
Sensing dissolved oxygen with microelectrodes: from steady state to transient conditions
Speaker:Professor Guy Renuault
Date:26 August 2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Toh Chee Seng
Abstract:

We have previously reported the successful development of a microelectrode oxygen sensor for oceanographic measurements.[1,2] Based on the steady state current for oxygen reduction at a Pt microdisc the sensor relies on a potentiostatic waveform to recondition the electrode surface in situ between measurements and on a stopped-flow cell to eliminate convection around the microelectrode. The amperometric response obtained was found to be stable and was used to record oxygen depth profiles in the ocean.[2] However the response did show some sensitivity to the movement of the sensor platform and for this reason we are now developing a fast amperometric sensor immune to hydrodynamic fluctuations.

This lecture will present the results of voltammetric and chronoamperometric experiments undertaken to investigate the oxygen reduction reaction at microdisc electrodes. The main objectives of the work were to study the reaction from sub-ms to 1 s, to determine if and how napp, the apparent number of electrons, depends on time and to design a new conditioning potentiostatic waveform to achieve reproducible O2 reduction transients. The study also aimed to probe the involvement of Faradaic and non-Faradaic processes, assess their contribution to the chronoamperometric response and tune the conditioning waveform to minimise their influence. The lecture will describe the methodology employed, the experimental approach chosen and attempts made to validate the results with available theory.

  1. Sosna, G. Denuault, R. W. Pascal, R. D. Prien and M. Mowlem, Sensors and Actuators B: Chemical, 2007, 123, 344-351.
  2. Sosna, G. Denuault, R. W. Pascal, R. D. Prien and M. Mowlem, Limnology and Oceanography: Methods, 2008, 6, 180-189.

 

Title:
Diastereoconvergent Formal Nucleophilic Substitution of Bromocyclopropanes en-route to Cyclopropanol and Cyclopropylamine Derivatives
Speaker:Professor Michael Rubin
Date:26 August 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS Lecture Theatre 3
Host:Associate Professor Roderick W. Bates
Abstract:

A diastereoconvergent formal nucleophilic substitution of bromocyclopropanes with oxygen-, sulfur-, and nitrogen-based nucleophiles will be described.  The reaction proceeds via in situ formation of a highly reactive cyclopropene intermediate and subsequent diastereoselective addition of a nucleophile across the strained C=C bond. Three alternative means of controlling the diastereoselectivity of addition have been demonstrated: (1) thermodynamically driven epimerization of enolizable carboxamides, (2) steric control by bulky substituents, and (3) directing effect of carboxamide or carboxylate functions.  A new cyclization strategy, based on the intramolecular version of this process will be disclosed, which allows for furnishing medium sized heterocycles, mimicking reverse turns and β-strands.  Elaboration of a highly diastereoselective protocol, leading to enantiomerically pure heterocyclic products from racemic cyclopropane precursors, will be disclosed and the relevant mechanistic implications will be suggested.

 

Title:
Isolated-FAMSD system consisting of modeling of oligomer proteins and ligand based drug design in the receptor
Speaker:Professor Hideaki Umeyama
Date:22 August 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Hajime Hirao
Abstract:

We have developed the modeling system for the oligomer proteins in addition to the isolated protein. Our method is based on the homology modeling, in which the Monte Carlo method is applied in the construction of the main chain and in the concept of local space homology. Our modeling program called FAMS is active in relation to the CASP contests during these ten years, and it has more powerful activity in adding the CIRCLE program, which estimates energetically the protein structure after the protein folding from a free energy point of view. Usually a protein has a function in the living things, and there are many cases interacting with the small molecules such as substrates or coenzymes. If a researcher recognizes the functional participation of a small molecule for his own target protein, he can easily estimate the function of his protein. During about 40 years, many proteins with low molecular weight ligand molecules have been analyzed from X-ray diffraction analyses. Such a small ligand binding site is useful to find a new drug as the competitive compound which may become antagonist or agonist. In those circumstances, we have developed the bioinformatics based ligand docking program called ChooseLD. This program has both functions of the structure-based drug design and the ligand-based drug design, and it includes an entirely new type algorism. Considering the potential-energy surface of the funnel type for the interaction between the target protein and a docking ligand, the compound docking for the target protein is assumed to be composed of the linear combination among many funnel types. Logical validity of the assumption of the linearity is indirectly confirmed by assessment in the comparison with other famous docking programs such as GOLD.  ChooseLD uses the functional group called finger prints based upon the ligand group consisting of many compounds in experimentally analyzed family proteins. In this case, the finger prints have 3D-coordinates, and are used as the base of Monte Carlo calculation for the docking ligand and the binding ligands to the family proteins, while the docking ligand molecule is also taken apart into finger prints with 3D-coordinates. Now, we are thinking that FAMS for the modeling of the oligomer proteins and the isolated protein, CIRCLE for the estimation of the stability of 3D-dimensional protein structures of the oligomer proteins and the isolated protein and ChooseLD for the bioinformatics based drug design in the in-silico screening should be combined organically around one web-site, if we want to perform the drug design rationally and efficiently. FAMS complex, CIRCLE and ChooseLD are in the state of the certificates of patent by In-Silico Science Company. Thus, we finished the pilot type program of the integrated system called Isolated-FAMSD, and we explain this pilot system in this seminar.

 

Title:
New Approaches to Molecular Imaging Using Nonlinear Optics: Transforming Diagnosis with Chemical Information 
Speaker:Professor Warren S Warren
Date:10 August 2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Tan Howe Siang 
Abstract:

Molecular imaging-the use of chemical signatures to image function instead of merely structure-promises to enable a new generation of clinical modalities that can revolutionize both diagnosis and treatment.  My lab works on new approaches in two specific modalities-magnetic resonance and nonlinear optical imaging- where a close coupling between basic physics on the one hand, and focused clinical questions on the other hand, enable new and important applications. 

In this talk I will focus on nonlinear optics.  Our lab has developed advanced femtosecond pulse shaping and detection technologies to access intrinsic nonlinear signatures that were not previously observable in tissue.  We have developed two such measurement techniques:  a spectral reshaping technique that can measure nonlinear dispersive or absorptive processes, and a pulse train shaping technique (essentially a modulated pump-probe spectroscopic technique) that is more sensitive, but restricted to absorptive contrast.  Applications to imaging hemoglobins and melanins in tissue by nonlinear absorption will be highlighted, including recent work published in Science Translational Medicine which could revolutionize melanoma diagnosis by improving the pathology “gold standard”.

 

Title:
Small Molecule Tools for Cell Biology and Cell Therapy
Speaker:Professor Motonari Uesugi
Date:10 August 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Brendan Orner
Abstract:

In human history, bioactive small molecules have had three primary uses: as medicines, agrochemicals, and biological tools. Among them, what our laboratory has done in the past was the discovery and use of biological tools. Our laboratory has been discovering and designing small organic molecules with unique activities to them as tools for biological investigation and manipulation.

In addition to tool discovery, our laboratory has recently become interested in exploring another application of small molecules: small molecule tools for cell therapy. Although small molecule drugs will continue to be important, cell therapy will be a powerful approach to curing difficult diseases that small molecule drugs are unable to handle. However, there are a number of potential problems in bringing cell therapy technologies to the clinic, including high cost, potential contamination, low stability, and tumorigenesis. Stable, completely defined small molecule tools, which are usually amenable to cost-effective mass production, may be able to help the clinical use of cell therapy.

Through screening chemical libraries, we have been discovering unique synthetic molecules that modulate or detect fundamental characteristics of human cells useful for cell therapy. Some of such molecules may serve as tools for cell engineering or cell therapy as well as basic cell biological research. This presentation provides a quick overview of our recent research programs with a special emphasis on the discovery and utilization of “adhesamine.” This dumbbell-shaped synthetic molecule enhanced attachment and growth of cells by binding to heparan sulfate on cell membrane and thereby clustering syndecan. Using this molecule as a lead, we were able to design small synthetic molecules with fibronectin-like properties, which boost culture, expansion, and transplantation of clinically useful cells.

Other small-molecule tools we newly discovered may be discussed in the presentation as well.

 

Title:
Enantiodivergent synthesis of P-chirogenic organophosphorus compounds: from chiral ligands, to clusters and coordination polymers
Speaker:Professor Sylvain Jugé
Date:4 August 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Professor Francois Mathey
Abstract:

Enantiomerically enriched organophosphorus compounds are useful as bioactive substances, ligands for asymmetric catalysis, organocatalysts, coordination polymers, stereoselective synthesis or as chiral counter-ions. Their stereoselective synthesis was usually achieved using mainly menthol, spartenin or ephedrin1 as chiral auxiliaries. However, only (-)-menthol and (-)-sparteine are naturally occuring, and the synthesis of the other optical antipode of an organophosphorus, requires strategies or the use of a more expensive surrogate. Whereas (+)- or (-)-ephedrine are cheaper and commercially available, the methodology derived offers the possibility to synthetize the both enantiomers starting from the same optical antipode.2

 Several strategies starting from (-)- or (-)-ephedrine were reported.2 The principle of the enantiodivergent synthesis is based on the diasteroselective formation of an oxazaphospholidine heterocycle, and then the regio- and stereoselective ring opening of the heterocycle by P-O bond cleavage. Subsequent electrophilic or nucleophilic reactions lead to one or the other enantiomer of the organophosphorus. The enantiodivergent synthesis was applied for the synthesis of diphosphines, clusters3 and coordination polymers.4

 1) C. Darcel, J. Uziel, S. Jugé in Phosphorus Ligands in Asymmetric Catalysis Synthesis and Applications, A. Börner  (ed.), 2008, Wiley-VCH. 2) F. Chaux, S. Frynas, H. Laureano, C. Salomon, G. Morata, M-L. Auclair, M. Stephan, R. Merdès, P. Richard, M-J. Ondel, J. C. Henryb J. Bayardon, C. Darcel, S. Jugé, C.R. Chimie 2010, 13, 1213-1226. 3) a) C. Salomon, D. Fortin, C. Darcel, S. Jugé, P. D. Harvey, J. Clust. Sci. 2009, 20(2) 267. b) C.  Salomon, S. Dal Molin D. Fortin,Y.  Mugnier, R. T. Boeré, S. Jugé, P. D. Harvey J. C. S., Dalton Transaction 2010, 39, 10068-10075. 4) C. Salomon, D.Fortin,  N. Khiri,  S. Jugé, P. D. Harvey, Eur. J. Inorg. Chem. 2011, 16, 2597-2609

 

Title:
Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone: Synthesis, Properties and Applications 
Speaker:Associate Professor Tirayut Vilaivan
Date:29 July 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Roderick Bates 
Abstract:

Peptide  nucleic  acid  (PNA)  is  a  completely-redesigned  oligonucleotide analogue with an electrostatically neutral peptide-like backbone instead of the sugar-phosphate. In addition to being able to recognize  both  DNA  and  RNA  with  high  affinity  and specificity, the uncharged backbone of PNA contributes to its many unique propertiesnot observed  in other classes of oligonucleotide analogues.  A  number  of  PNA  structures  have  been  proposed  to dates,  but  few  of  them  offer  additional  benefits  over  the  original  PNA  systems  developed  since  1991  in  terms  of  binding  affinity, specificity and other   properties.   We   describe   herein   a   new conformationally constrained  analogue  of  PNA  carrying  an alternating  α/β  amino  acid  backbone  consisting  of  nucleobase-subtituted proline and (1S,2S)-2-aminocyclopentanecarboxylic acid (acpcPNA). The acpcPNA can form highlystable antiparallel hybrids with both DNA and RNA  in  a  sequence-specific  fashion. They  also  show  several  unusual  features not observed in other PNA and DNA analogues including the preference for  pairing  with  DNA  over  RNA  and  the inability to form self-pairing hybrids. Applications of the new PNA as probes for DNA sequence  determination have also been demonstrated. 

 

Title:
Novel Bromination Reactions in Organic Synthesis
Speaker:Assistant Professor Yeung Ying Yeung
Date:20 July 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Xing Bengang 
Abstract:

Halogenation is an important class of organic transformation. Over the pass decades, reactions including cohalogenation, haloetherification, halolactonization and polyene cyclization are well documented. These reactions have been applied in many natural products and drug molecules synthesis. One of the research focuses in our research group is on the development of novel bromination using N-bromosuccinimide (NBS), an easy handle and inexpensive halogen source. Recently, we have developed a catalyst-free electrophilic aminoalkoxylation reaction. In this reaction, aminoether derivatives were prepared by a one-pot reaction using olefin, NBS, amide, and cyclic ether. Other than aminoalkoxylation, we have studied the use of chiral amino-thiocarbamate catalyst in asymmetric bromocyclization reaction. Various chiral, non-racemic ϒ-lactones and pyrrolidines were prepared with good yields and ees.

 

Title:
Creation of New Medicines: How The Medicinal Chemist Can Transform Lives with Good Science, Teamwork and Small Resources
Speaker:Dr Brian Dymock
Date:18 July 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Roderick W. Bates
Abstract:

New medicines are badly needed by society to combat poorly treated diseases and relieve suffering.  Unfortunately the track record of the pharmaceutical industry in recent times has been less than satisfactory with rising costs and reduced productivity. Merger activity between companies is a significant contributing factor which is itself driven by the pressure from the looming problem of the ‘patent cliff’ where prescription drugs reach the end of their patent protection and become ‘generic’ with an accompanying dramatic drop in the price. In one sense this price drop is great for health authorities and patients but in from another point of view it is bad for patients in the long run since it results in less R+D investment and fewer new medicines coming through. Inevitably, drug discovery scientists must face up to the fact that the pharma industry has contracted with less R+D investment now available. Hence we need to be smarter about how drugs are discovered, making optimal use of available resources.

What can the medicinal chemist do to achieve greater efficiency?  Medicinal chemists are at the heart of preclinical drug discovery from the identification of a biological target through to preclinical development and still involved during clinical development by ensuring consistent supplies of large amounts of drug product for acceptable cost and quality. In the preclinical phase medicinal chemists can use their understanding of molecular interactions, stereoelectronics, conformational and physiochemistry to focus synthetic efforts on the target compounds most likely to meet their objectives. For example, synthesizing compounds with high LogP may result in increases in potency in vitro but may not result in the required solubility or cell penetration.  This presentation will discuss some recent reports in the literature regarding efficiency in drug discovery and molecular design and illustrate these topics with examples from S*BIO’s home-grown drug discovery efforts which have resulted in 4 new molecular entities (NCEs) entering the clinic and two other clinical candidates in preclinical development.

 

Title:
Quantum Chemical Modeling of Co-C Bond Activation in B12-Dependent Enzymes
Speaker:Professor Pawel M. Kozlowski
Date:13 July 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Hirao Hajime
Abstract:

The origin of the enormous catalytic activity of coenzyme B12-dependent enzymes continues to be an outstanding problem in bioinorganic chemistry. During enzymatic catalysis the Co-C bond of coenzyme B12 (AdoCbl) is cleaved homolytically, leading to the formation of the 5’-deoxyadenosyl radical and cob(II)alamin.  The rate of enzymatically accelerated homolytic cobalt-carbon bond cleavage of AdoCbl exceeds the rate observed in aqueous solution by about 12 orders of magnitude as a consequence of the coenzyme interaction with the substrate in the presence of apoenzyme.  Despite the great effort that has been devoted to this problem, the mechanism of the catalytic activation is poorly understood. To the extent it has been addressed experimentally, evidence from model systems indicate that steric hindrance around coordinated alkyl ligands leads to a higher homolysis rate. Different models have been suggested, but none can be considered as fully satisfactory in light of a large body of experimental results.

In my presentation I will summarize recent progress in computational modeling of the catalytic activation of cobalt-carbon bond cleavage. The growing interest in modeling the structure and electronic properties of AdoCbl has demonstrated that computer simulations, in particular density functional theory (DFT) can be an important part of coenzyme B12 research. 

 

Title:
Green Tea Polyphenols: Structure Modification and Applications in Food and Natural Health Products 
Speaker:Dr Ying Joy Zhong
Date:6 July 2011 
Time:10.45am to 12.15pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Xing Bengang 
Abstract:

Tea is the second most popular beverage worldwide and a major source of dietary polyphenols that are known to render a myriad of health benefits. Epigallocatechin gallate (EGCG), the predominant polyphenol in green tea and a powerful antioxidant, has been proposed as a functional ingredient in the food and health-related industries. However, the hydrophilic nature of EGCG restricts its use in lipophilic media and its absorption by the cells in vivo. Structure modification of EGCG via esterification with long-chain fatty acids can serve as a useful tool to enhance its lipophilicity and therefore improve its bioactivities in more diverse food and biological systems and its bioavailability in the body. Additional advantages or synergism may be rendered by incorporation of the health beneficial omega 3 fatty acids.

 

Title:
Molecular Group 2 Metal(I) Complexes: From Chemical Landmarks to Versatile Reagents
Speaker:Professor Cameron Jones
Date:29 June 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Dragoslav Vidovic
Abstract:

The chemistry of compounds containing p-block elements in very low oxidation states has rapidly advanced over the last two decades.  More than being just chemical curiosities, these species have begun to find a variety of applications in synthesis, small molecule activations etc.1 In 2007, we extended this field to the s-block with the preparation of the first room temperature stable molecular compounds containing magnesium-magnesium covalent bonds, viz. LMgMgL (L = bulky guanidinate or b-diketiminate 1).2 Subsequently, we have found such magnesium(I) compounds to have considerable utility as soluble, selective, stoichiometric reducing agents in organic and inorganic synthesis. In many cases, the products obtained from reactions involving these compounds are not accessible using traditional reducing agents, e.g. alkali metals or SmI2. This is especially so for reductions of p-block element precursors, which have yielded a variety of unprecedented low oxidation state group 13 and 14 complex types, e.g. 2 and 3.3 In this lecture our recent efforts to further develop the reaction chemistry of magnesium(I) dimers will be presented.

1. Power, P.P. Nature 2010, 463, 171.

2. (a) Green, S.P.; Jones, C.; Stasch, A. Science 2007, 305, 1136; (b) Bonyhady, S.J.; Jones, C.; Nembenna, S.; Stasch, A.; Edwards A.J.; McIntyre, G.J. Chem. Eur. J. 2010, 16, 938.

3. (a) Sidiropoulos, A.; Jones, C.; Stasch, A.; Klein, S.; Frenking, G. Angew. Chem. Int. Ed. 2009, 48, 9701; (b) Bonhady, S.J.; Collis, D.; Frenking, G.; Holzmann, N.; Jones, C.; Stasch, A. Nature Chem., 2010, 2, 865.

 

Title:
Development of Novel and Efficient Transformations to Construct Carbon-Carbon Bonds Using Group 7 Transiton Metal Catalysts
Speaker:Assistant Professor Yoichiro Kuninobu
Date:22 June 2011 
Time:3.00pm to 4.00pm
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Naohiko Yoshikai 
Abstract:

During a long history of the development of transition metal catalyzed reactions, there have been several metals, which have rarely been used in synthetic organic chemistry.  One of them is rhenium compounds.  When I started my academic career at the end of 2003, the use of rhenium catalysts have almost limited to oxidation reactions, and only a few examples of carbon-carbon bond forming reactions have been reported.  I focused on rhenium complexes, which have rarely been used in synthetic organic chemistry, and identified their characteristic reactivities.  By using the rhenium complexes as catalysts, I discovered transformations based on the cleavage of inactive bonds, such as carbon-hydrogen and carbon-carbon bonds.  Such transformations are recognized as key methods to realize efficient and powerful reactions.  I also revealed novel regio- and/or stereodefined cycloaddition reactions.  In addition, I also developed useful reactions using a manganese complex as a catalyst.

 

Title:
Design and Syntheses of Cluster Molecules for Catalytic Reactions
Speaker:Assistant Professor Kohei Endo
Date:22 June 2011 
Time:12.00pm to 3.00pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Shunsuke Chiba
Abstract:

The development of cluster molecules is a recent challenge in natural science to control precisely large molecules. We are working on a new benchmark of cluster molecules based on organic chemistry; the central structure of carborane, namely multiborylmethane, shows a unique reactivity in Suzuki–Miyaura cross-coupling reaction. Another strategy for multimetallic complexes exemplifies the efficient construction of chiral catalysts in asymmetric alkylation reaction using organometallic reagents. The representatives in these strategies will be shown in the presentation.

 

Title:
Recovering Proteins from Cereal Grains
Speaker:Dr Ilankovan Paraman
Date:30 May 2011 
Time:10.45am to 12.15pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Li Tianhu
Abstract:

Using plants as bioreactors to produce pharmaceuticals and industrial proteins, often referred to as molecular farming, continues to be a focus of biotech research.  When using corn (maize) grain as a production host, the proteins are often expressed tissue-specific in germ (embryo) or endosperm.  Proteins can be recovered and purified by simple fractionation procedures.  These processes remove corn-derived impurities at an early stage of processing thereby simplifying downstream protein processing.  After extracting the recombinant protein, the starch-rich spent solids could be used as fermentation feedstock to produce fuel ethanol and other industrial chemicals.  Successful processing strategies need to consider two key issues: (i) selecting processing conditions compatible to the protein of interest; and (ii) utilizing the protein-lean coproducts through integrated biorefineries producing marketable coproducts that are not used for food. Such integration is vital to enhancing the economics of protein recovery and maximizing co-product returns.

 

Title:
Unprecedented 3D Molecular Architectures: Folding into Shape
Speaker:Assistant Professor Hee-Seung Lee
Date:25 May 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Brendan Orner
Abstract:

Molecular  self-assembly  is  the  spontaneous  assembly  of  molecules  into  structured  aggregates  by which nature builds complex functional systems. While numerous examples have focused on 2D self-assembly  to understand  the  underlying mechanism  and  mimic  this  process  to  create  artificial  nano and  microstructures,  a  limited  progress  has  been  made  toward  3D  self-assembly  on  the  molecular level.  This  lack  of  progress  is  partially  due  to  the  difficultly  of  designing  and  using  nondirectional noncovalent  interactions,  such  as  van  der  Waals  and  hydrophobic  interactions,  in  synthetic, nonbiological molecular systems. Thus, we sought to establish a set of self-assembling components that  could  be  linked  to  observable  3D  shapes  by  which  the  governing  parameters  of  self-assembly could be disentangled and tractable. Recently, we discovered that artificial protein fragments (helical β-peptide foldamers) with well-defined hydrophobic surfaces self-assembled to form unprecedented 3D molecular architectures in a controlled manner in aqueous solution. We anticipate that our strategy can  be  a  starting  point  for  the  rational  design  of  3D  organic  molecular  architectures  with  various functions. Furthermore, the self-assembly behavior of artificial protein fragments will be relevant for the development of synthetic foldamer proteins.

 

Title:
The Science of Food
Speaker:Dr Allan Lim
Date:20 May 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Associate Professor Li Tianhu 
Abstract:

Food is not only vital to the survival of human beings, it is also deeply integrated into the culture of each civilization.  In Asia, food embodies art, family, pleasure and wellbeing.  For those who are interested in the chemistry of food, there is still a lot to be discovered, especially in Asian food.  This presentation will briefly highlight three areas which will challenge all chemists and biologists:

Taste: the science of taste has revolutionized the food industry.  Scientists are now beginning to understand how humans perceive saltines, sweetness, bitterness and sourness.  With the use of high throughput screening, molecules that are more potent than monosodium glutamate and sucrose are already available to food companies to develop food with less monosodium glutamate and beverage with less sugar.

Fermentation:  Asians started fermenting foods since prehistoric times, for preservation, taste enhancement and nutrition.  Many traditional fermentation processes such as soya sauce have been industrialized.  However, it is only in recent years that scientists began using proteomic tools to discover novel bioactive peptides molecules in fermented foods, paving the way for new drugs and nutraceuticals.

Antimicrobials:  Consumers today are pushing food companies to replace chemical preservatives like benzoates and sorbates with natural ingredients such as essential oils, bacteriocins and organic acids.  In addition, food scientists and packaging engineers are exploring the use of active packaging as complementary or alternative approach to chemical preservation. 


 

Title:
Navigating the Potential Energy Surface of Liquid Water
Speaker:Dr Richard Henchman
Date:28 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Zhang Dawei
Abstract:

Controversy reigns regarding water's structure and dynamics. Tetrahedral structure with a component of broken hydrogen bonds is not consistent with all experimental data. Here, a new definition for a hydrogen bond is applied to give a detailed characterisation of the structure and dynamics of liquid water. The definition equates a hydrogen bond with an energy well in the potential energy surface, sharply resolves transition states in hydrogen-bond switching, avoids arbitrary parameters and takes into account correlations. In addition to the dominant tetrahedral hydrogen-bond coordination, it reveals that there are smaller trigonal and trigonal bipyramidal components in almost equal proportions and that the fraction of broken hydrogen bonds is very small. These non-tetrahedral components are observed to have higher enthalpy, entropy, density and dynamics. Hydrogen-bond switching proceeds via a decrease and increase in hydrogen bonds of the respective initial and final acceptors. Three mechanisms of hydrogen-bond switching are detected, depending on whether the donor and new acceptor share a hydrogen bond prior to switching.

 

Title:
Asymmetric Reactions Catalyzed by Lewis Basic Amines
Speaker:Professor Chen Ying-Chun
Date:20 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Robin Chi Yonggui
Abstract:

Over the past decade, great achievements have been made by using small organic molecules as the catalysts, especially in the field of asymmetric synthesis. We concentrated the research work on asymmetric organocatalysis since the beginning of independent investigation in 2004. We have reported efficient Mannich reactions mediated by thiourea compounds via hydrogen bonding interaction. We also developed the highly successful 9-amino-9-deoxyepicinchona alkaloids as iminiun catalysts for alfa,beta-unsaturated ketones. Here we will present our recent efforts in the development of Diels-Alder-type or cascade reactions for the efficient constructions of complex carbo- and heterocycles by the catalysis of chiral secondary amines, via either enamine, dienamine or even newly discovered trienamine activation modes. In addition, we will also discuss the asymmetric dynamic transformations of Morita-Baylis-Hillman carbonates in the presence of chiral tertiary amines, especially with modified cinchona alkaloids. 

 

Title:
Understanding and Optimizing the Electrochemical Evolution of Oxygen on Metal Oxide Surfaces 
Speaker:Dr Yeo Boon Siang Jason
Date:19 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Martin Pumera
Abstract:

Efficient electrochemical splitting of H2O to H2 and O2 is an important goal in the quest for a renewable source of energy. A major inefficiency of this process is the high overpotential required for the anodic oxygen evolution reaction (2H2O → O2 + 4e- + 4H+, OER). Understanding the mechanism of the OER will help to identify the processes responsible for its overpotential and their relationship to the anode composition and morphology. We have combined in-situ surface-enhanced Raman spectroscopy (SERS), H/D isotope labeling and electrochemical methods to detect intermediates formed during OER on a gold anode. Our work shows that the surface of gold oxidizes at anodic potentials and that hydroperoxy species (OOH) are formed at the onset of O2 evolution, in both acidic and basic electrolytes. We conclude that OOH species are formed most likely via the processes O + OH ® OOH or O + H2O ® OOH + H+ + e, in close agreement with previous theoretical calculations.

Cobalt oxide is an earth abundant material and has been used for water splitting. We investigate the oxygen evolution reaction occurring on the surface of cobalt oxide supported on various metal substrates. The turnover frequency of OER exhibited by a sub-monolayer of cobalt oxide adsorbed on gold is around forty times higher than that of bulk cobalt oxide. The higher OER activity of cobalt oxide deposited on Au is attributed to an increase in fraction of the Co sites present as CoIV cations, a state of cobalt believed to be essential for OER to occur. A mechanism by which CoIV cations may contribute to OER is proposed and discussed.

 

Title:
Modular Functionalization of Ribonucleopeptide Assemblies
Speaker:Professor Takashi Morii
Date:13 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room 
Host:Assistant Professor Brendan Orner
Abstract:

A stable complex of a peptide and RNA, ribonucleopeptide (RNP), provides a new framework to construct a macromolecular receptor for small molecules. The RRE RNA and the Rev peptide form a structurally well-characterized stable RNP complex that is suitable for a stepwise functionalization. In vitro selection of the RNP pool originating from an RRE-based RNA library and the Rev peptide affords RNP receptors specific for nucleotide triphosphates or the phosphotyrosine residue. The RNP receptor functionalized by a fluorophore-labeled Rev peptide exerts optical signals associated with the ligand binding events. Replacing the Rev peptide of the ATP-binding RNP with a fluorophore-modified Rev peptide affords a series of fluorescent ATP sensors. This strategy to generate tailor-made fluorescent sensors is applied for a selective detection of a specific phosphorylated tyrosine residue within a defined amino acid sequence. Structural aspects for the function of RNP receptors and sensors will be discussed.

 

Title:
Self-Assembly of Zein into Nanoscale Soft Structures
Speaker:Dr Yi Wang
Date:12 April 2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS MAS Executive Classroom 1  
Host:Associate Professor Li Tianhu
Abstract:

Self-assembly of soft materials, such as surfactants, proteins, lipids, and DNA, can build periodic nanoscale structures with tunable sizes and shapes. Evaporation-induced self-assembly (EISA) of zein, a major protein of corn, was investigated to gain understanding on the formation of various zein microstructures, including spheres, biocontinuous structures and lamellar films. Such soft structures may find wide applications in foods, agriculture, and biomedical engineering. A phase diagram was built to identify the experimental conditions leading to the formation of various mesophases. Boundary lines were fitted with models derived from Flory-Huggins solution theory. Microstructure was investigated by SEM, FIB, TEM, and FTIR. 

 

Title:
The Outlook for Energy: A View to 2030
Speaker:Rob Gardner
Date:11 April 2011 
Time:2.00pm to 3.00pm 
Venue:NTU SPMS Lecture Theatre 3, Level 3
Host:Associate Professor Roderick W. Bates
Abstract:

The world faces tremendous energy challenges. Energy enables economic growth and plays a key role in advancing social progress. Over the next two decades, demand for energy is forecast to rise dramatically across the globe, as populations and economies grow. Meeting the growing need for reliable and affordable energy - safely and with minimal environmental impact - is a key challenge facing governments and societies worldwide. Success will require international cooperation and a tremendous investment in new technologies to enable the world to expand its energy choices, improve efficiency and reduce emissions.

Key topics to be covered:

•   Energy supply/demand outlook to 2030
•   Trends and new developments in world oil and gas supply
•   Availability of energy sources, including fossil fuels, nuclear power and renewable energy
•   Electricity demand growth and implications for power generation
•   The growing role of natural gas in the energy mix
•   Energy-related CO2 emissions to 2030

 

Title:
Recent Progress in Catalyzed Addition Reactions of H-P(O) Compounds to Alkynes
Speaker:Professor Masato Tanaka
Date:1 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor François Mathey
Abstract:

Some ten years ago an interesting regiochemical reversal induced by Ph2P(O)OH in Pd-catalyzed addition of Ph2P(O)H with terminal acetylenes was disclosed and [Ph2P(O)-Pd-OP(O)Ph2] species was proposed as key intermediate.1 During the course of addition-carbocyclization of a,w-diynes with HP(O)Ph2,2 however, we have come across unexpected result that suggests the real active species is a zwitterionic palladium complex formed though hydrogen bonding with ligated P(O)Ph2 moiety with a Ph2P(O)OH (Scheme 1).3 Detailed study has shown (1) HP(O)Ph2 is activated by palladium center through oxidative addition, (2) resulting species interacts with Ph2P(O)OH through hydrogen bonding, forming an intermediate having PPh2(O-H-OP(O)Ph2), which is a sort of phosphine ligand and prone to dissociate to generate a vacant coorination site, and (3) then an alkyne occupies the site to undergo insertion. Thus, the whole process is carried by duo of palladium and Ph2P(O)OH. This type dual activation facilitates the catalysis more efficiently as compared with the regime without Ph2P(O)OH or other Brønsted acids and has been found to successfully work in addition of dialkylphosphine oxide to alkynes (Table 1). Furthermore, similar dual activation was found with nickel and Brønsted acids and allowed the addition of dialkylphosphine oxide to take place very efficiently at room temperature.

 

Title:
Calculating, Modeling & Analyzing Molecular Vibrational Motion in Multidimensional Spectroscopy
Speaker:Professor Yoshitaka Tanimura
Date:30 March 2011 
Time:3.00pm to 4.30pm
Venue:NTU SPMS MAS Executive Classroom 1
Host:Assistant Professor Tan Howe Siang
Abstract:

Spectral line shapes in a condensed phase contain information from various dynamic processes that modulate the transition energy, such as microscopic dynamics, inter and intramolecular couplings, and solvent dynamics. In this talk, we explore and describe the roles of different physical phenomena that arise from the peculiarities of the system-bath coupling in multidimensional spectra.  For this purpose, we employed the Brownian oscillator model with the nonlinear system-bath interaction. Using the hierarchy formalism, we could precisely calculate multidimensional spectra for a single and multimode anharmonic system for inter- and intramolecular vibrational modes.

We examined the capability of the present approach by comparing the signals of two- and three-dimensional IR vibrational spectroscopy obtained from experiments and molecular dynamics simulations. 

 

Title:
Bioactive Response of Cultured Hepatocarcinoma Cells and Adipocytes to Triterpenoids Derived from Selective Medicinal Plants
Speaker:Assistant Professor Popovich, David Glen
Date:25 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Li Tianhu
Abstract:

Bioassay guided extraction has been employed to obtain bioactive compounds from a variety of plants common in traditional Chinese diet and medicine. Three different cultured cell lines derived from hepatic, intestinal carcinoma and adipose cells are used to assess the activity of extracted materials to induce apoptosis or necrosis, reduce lipid accumulation and increase adipocytokines expression, as well as to estimate bioavailability. Once bioactivity is detected and the phytochemical profile has been established by HPLC-MS analysis, the extracts are typically fractionated based on the polarity of the resultant HPLC profile. Fractions of interests are then concentrated and further tested for activity and potential additive, antagonistic synergistic response when combined with other extracts, phytochemicals or pharmaceuticals. This presentation will focus on the bioactive determination of triterpenoids recovered from medicinal plants such as American ginseng (Panax quinquefolius), Asian ginseng (Panax ginseng), soy (Glycine Max) and bitter melon (Momordica charantia). These plants have a long history of use and contain complex triterpenoid compositions that possess multiple activities such as cytotoxicity and induction of apoptotic cell death, ability to differentiate hepatocarcinoma cells, reduce lipid accumulation and increase adiponectin secretion from the adipocyte. For example, both American ginseng and Asian ginseng contain similar dammarane type triterpenoids commonly known as ginsenosides that differs in proportions. Asian ginseng however has been shown to reduce lipid accumulation and increase adiponectin secretion from the adipocytes at lower concentration than American ginseng. In addition, oleanane triterpenoids from soy have varying cytotoxicity that is dependent on chemical structure. The focus of the research is to ultimately classify bioactive response based on the chemical structure of the compound and to provide evidence-based preclinical data that would allow the development of novel products that may be used to combat metabolic-related disease such as insulin resistance.

 

Title:
Introduction to the NTU Protein Production Platform
Speaker:Assistant Professor Tobias Carl Cornvik
Date:24 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Xing Bengang
Abstract:

In 2010 a protein production platform was established as part of a structural biology effort headed by Prof Pär Nordlund. It has been available for researchers at SBS and we have to date worked with more than 20 PIs, helping them to produce their protein(s) of interest. To date we have produce approximately 500 protein batches and cloned more than 2500 constructs.

We employ a very successful multi-construct approach to increase the success rate of producing soluble proteins in E.coli and we typically achieve desired purity after a two-step purification consisting of IMAC and SEC.

The platform uses high-throughput technologies with a cloning and screening capacity of roughly 2*96 constructs per month and a large-scale purification capacity of 12 proteins per week.

We are now offering our services to other schools outside SBS and in my presentation I will describe the technologies used in the platform and how the researchers will submit their targets.

 

Title:
How Proteins Understand Genomes
Speaker:Dr Ralf Jauch
Date:23 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

Many transcription factor (TF) proteins bind short, degenerate and often indistinguishable DNA sequences suggesting that they are biochemically capable of binding a large fraction of the genome. Yet, individual TFs are functionally non-redundant or even antagonize each other and execute distinctive gene expression programs.  Thus, to achieve selectivity, combinations of TFs must team up and cooperate to specifically target genomic control regions and regulate gene expression. We seek to understand how TF cooperativity is brought about on the level of DNA recognition. To this end, we study the importance of constraint DNA motif arrangements, effects of protein binding on DNA structure as well as allosteric changes of variant DNA ligands on protein contact interfaces. By using computational, biochemical, biophysical and crystallographic methods we investigate the make-up of genomic control regions and seek to identify elements, within the bound DNA sequences as well as within the TF, that determine specificity in the process of gene regulation. I will discuss structural and functional work on the Sox, POU, Pax and Smad TF families and demonstrate how the rational re-engineering of TF cooperation can lead to dramatic functional swaps in vivo. I will also touch on our efforts to assess strategies for the targeted modulation of TF activity using small molecules. 

 

Title:
“Multi-scale” Simulation of Processes in Membrane Proteins and Biomembranes: Methods and Applications
Speaker:Professor Qiang Cui
Date:16 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Lee Soo Ying
Abstract:

I’ll discuss a number of topics that represent our efforts in developing reliable molecular models for describing chemical and physical processes in membrane proteins and biomembranes. This is an exciting yet challenging research area because of the multiple length and time scales that are present in the relevant problems. As an example of chemical processes in membrane proteins, I’ll discuss the problem of proton pumping, several key mechanistic questions of interest and how sophisticated QM/MM simulations can help glean new insights. As an example of problems that feature very different scales, I’ll discuss the development of coarse-grained (both particle and continuum) models that hold the promise of better understanding membrane deformations induced by amphiphiles, peptides and proteins, which are implicated in many fascinating membrane-mediate processes, such as mechanosensation, membrane translocation and membrane fusion. 

 

Title:
Structure and Dynamics of Buried Interfaces of Nanopaticles, Thin Films and Biological Cells Probed by Nonlinear Light Scattering
Speaker:Professor Hai-Lung Dai
Date:15 March 2011 
Time:4.00pm to 5.00pm 
Venue:NTU SPMS MAS Executive Classroom 1 
Host:Professor Lee Soo Ying
Abstract:

The surface of nanometer and micron size particles, including nanoparticles and biological cells, in colloidal environments can be functionalized through molecular adsorption and chemical modification for specific technology applications. Knowing what is the chemical composition and structure at the surface of the particles buried deep in the colloid is critical to fundamental understanding of their properties and as well as their technology development. For molecular thin films, the electrical and mechanical properties often depend critically on the structure of the interfacial layer between the film and the substrate. Probing the small quantity of molecules at the interfacial layer in the background of the huge bulk, on the other hand, presents an experimental challenge.

Nonlinear optical phenomena such as Second Harmonic Generation (SHG) has unique symmetry properties that can be used to discriminate one single layer of ordered molecules from the massive background of randomly oriented molecules, and subsequently can be used to detect the interfacial layer buried underneath the condensed media. The coverage, energy, and even structure of the molecules adsorbed at the surface of particles immersed in a colloid can be determined by SHG. This has been demonstrated for a variety of colloidal particles, including nanoparticles and biological cells. In thin films of organic semiconducting molecules and ionic liquids, it is found that the interfacial layer can be ordered due to surface corrugation or in response to external field. SHG can even be used to examine the membrane of living biological cells, monitoring molecular adsorption and transport in real time. 

 

Title:
Assembling Small Molecules for Disrupting and Detecting Protein-Protein Interactions
Speaker:Associate Professor Junko Ohkanda
Date:9 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

Protein-protein interactions (PPIs) play a critical role in signaling networks that regulate numerous biological processes, such as proliferation, differentiation, and apoptosis. Low-molecular-weight inhibitors for PPIs are highly desirable due to their potential for application in pharmacology, however, disrupting such interactions by "drug-like" small molecules remains a difficult challenge because of the large and flat interfaces involved in PPIs.  Our strategy in developing synthetic organic agents for disrupting PPIs is based on the module assembly approach, where relatively small module compounds are designed to bind to a local protein surface area, and are assembled by various means, for example by covalent linking, to create a multivalent agent that is more capable of surface recognition than each individual compound.  In this presentation, the details of a proof-of-concept study on protein prenyltransferase inhibitors will be discussed. The inhibitors designed through the module assembly significantly disrupted the PPI, and showed dual inhibition potency for the enzymes sharing a common surface structure. 

 

Title:
Mode of Action and Possible Real Producers of the Marine Natural Product Norzoanthamine, A Promising Candidate for Osteoporosis
Speaker:Dr Seketsu Fukuzawa
Date:3 March 2011 
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Koichi Narasaka
Abstract:

Norzoanthamine, isolated from the colonial zoanthid Zoanthus sp. has been known to suppress the decrease in femoral weight and bone biomechanical parameters caused by ovariectomy. The results of cell response assays against murine mesenchymal stem cells suggested that norzoanthamine does not affect osteoblastic differentiation, because there was no change in the alkaline phosphatase activity, while the total collagen increased in a long-term cell culture. This phenomenon is apparently caused by the suppression of collagen degradation, rather than the acceleration of collagen production. Furthermore, norzoanthamine significantly accelerates the formation of the collagen-hydroxyapatite composite, an elemental structure of bone tissue. We found that more collagen hydroxyapatite composite was formed when more collagen was present, and this represents a significant mode of action for norzoanthamine. Therefore we hypothesize that the reported bone mechanical strength enhancement is caused by collagen-norzoanthamine supramolecular association. The facts that norzoanthamine is nontoxic and that it has a collagen protective activity indicate that it may provide significant therapeutic benefits. In particular, it may be a promising drug candidate for osteoporosis treatment and prevention.

Since Zoanthus sp. is a boneless cnidarian, the described above functions are directly irrelevant to the host animal. A significant point is that norzoanthamine did not inhibit protease activity, but rather, it protected the substract proteins from proteolytic cleavage. This protective effect is more pronounced in substrates with a longer peptide chain length, and thus it exhibits a kind of cluster effect. The marine invertebrate, Zoanthus sp. is found in tropical coral reefs. These organisms are exposed to external stresses, such as UV light in intense sunshine. Norzoanthamine could protect skeletal proteins in the host animal bodies from external stresses and possibly enhance survival. Although thousands of natural products have been isolated from marine organisms, there are few compounds that resemble norzoanthamine either structurally or functionally. In the course of our effort to clarify the biological function of norzoanthamine by investigating its distribution within the animal using MALDI imaging mass spectrometry, a fungus was isolated as the predominant symbiont of the zoanthid, and production of norzoanthamine by its laboratory culture was confirmed by mass spectroscopic analyses. 

 

Title:
Navigating the Potential Energy Surface of Liquid Water
Speaker:Dr Richard Henchman
Date:28 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Zhang Dawei
Abstract:

Controversy reigns regarding water's structure and dynamics. Tetrahedral structure with a component of broken hydrogen bonds is not consistent with all experimental data. Here, a new definition for a hydrogen bond is applied to give a detailed characterisation of the structure and dynamics of liquid water. The definition equates a hydrogen bond with an energy well in the potential energy surface, sharply resolves transition states in hydrogen-bond switching, avoids arbitrary parameters and takes into account correlations. In addition to the dominant tetrahedral hydrogen-bond coordination, it reveals that there are smaller trigonal and trigonal bipyramidal components in almost equal proportions and that the fraction of broken hydrogen bonds is very small. These non-tetrahedral components are observed to have higher enthalpy, entropy, density and dynamics. Hydrogen-bond switching proceeds via a decrease and increase in hydrogen bonds of the respective initial and final acceptors. Three mechanisms of hydrogen-bond switching are detected, depending on whether the donor and new acceptor share a hydrogen bond prior to switching

 

Title:
Asymmetric Reactions Catalyzed by Lewis Basic Amines
Speaker:Professor Chen Ying-Chun
Date:20 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Robin Chi Yonggui
Abstract:

Over the past decade, great achievements have been made by using small organic molecules as the catalysts, especially in the field of asymmetric synthesis. We concentrated the research work on asymmetric organocatalysis since the beginning of independent investigation in 2004. We have reported efficient Mannich reactions mediated by thiourea compounds via hydrogen bonding interaction. We also developed the highly successful 9-amino-9-deoxyepicinchona alkaloids as iminiun catalysts for alfa,beta-unsaturated ketones. Here we will present our recent efforts in the development of Diels-Alder-type or cascade reactions for the efficient constructions of complex carbo- and heterocycles by the catalysis of chiral secondary amines, via either enamine, dienamine or even newly discovered trienamine activation modes. In addition, we will also discuss the asymmetric dynamic transformations of Morita-Baylis-Hillman carbonates in the presence of chiral tertiary amines, especially with modified cinchona alkaloids. 

 

Title:
Understanding and Optimizing the Electrochemical Evolution of Oxygen on Metal Oxide Surfaces 
Speaker:Dr Yeo Boon Siang Jason
Date:19 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Martin Pumera
Abstract:

Efficient electrochemical splitting of H2O to H2 and O2 is an important goal in the quest for a renewable source of energy. A major inefficiency of this process is the high overpotential required for the anodic oxygen evolution reaction (2H2O → O2 + 4e- + 4H+, OER). Understanding the mechanism of the OER will help to identify the processes responsible for its overpotential and their relationship to the anode composition and morphology. We have combined in-situ surface-enhanced Raman spectroscopy (SERS), H/D isotope labeling and electrochemical methods to detect intermediates formed during OER on a gold anode. Our work shows that the surface of gold oxidizes at anodic potentials and that hydroperoxy species (OOH) are formed at the onset of O2 evolution, in both acidic and basic electrolytes. We conclude that OOH species are formed most likely via the processes O + OH ® OOH or O + H2O ® OOH + H+ + e, in close agreement with previous theoretical calculations.

Cobalt oxide is an earth abundant material and has been used for water splitting. We investigate the oxygen evolution reaction occurring on the surface of cobalt oxide supported on various metal substrates. The turnover frequency of OER exhibited by a sub-monolayer of cobalt oxide adsorbed on gold is around forty times higher than that of bulk cobalt oxide. The higher OER activity of cobalt oxide deposited on Au is attributed to an increase in fraction of the Co sites present as CoIV cations, a state of cobalt believed to be essential for OER to occur. A mechanism by which CoIV cations may contribute to OER is proposed and discussed.

 

Title:
Modular Functionalization of Ribonucleopeptide Assemblies
Speaker:Professor Takashi Morii
Date:13 April 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

A stable complex of a peptide and RNA, ribonucleopeptide (RNP), provides a new framework to construct a macromolecular receptor for small molecules. The RRE RNA and the Rev peptide form a structurally well-characterized stable RNP complex that is suitable for a stepwise functionalization. In vitro selection of the RNP pool originating from an RRE-based RNA library and the Rev peptide affords RNP receptors specific for nucleotide triphosphates or the phosphotyrosine residue. The RNP receptor functionalized by a fluorophore-labeled Rev peptide exerts optical signals associated with the ligand binding events. Replacing the Rev peptide of the ATP-binding RNP with a fluorophore-modified Rev peptide affords a series of fluorescent ATP sensors. This strategy to generate tailor-made fluorescent sensors is applied for a selective detection of a specific phosphorylated tyrosine residue within a defined amino acid sequence. Structural aspects for the function of RNP receptors and sensors will be discussed.

 

Title:
Self-Assembly of Zein into Nanoscale Soft Structures
Speaker:Dr Yi Wang
Date:11 April 2011 
Time:2.00pm to 3.00pm
Venue:NTU SPMS MAS Executive Classroom 1 
Host:Associate Professor Li Tianhu
Abstract:

Self-assembly of soft materials, such as surfactants, proteins, lipids, and DNA, can build periodic nanoscale structures with tunable sizes and shapes. Evaporation-induced self-assembly (EISA) of zein, a major protein of corn, was investigated to gain understanding on the formation of various zein microstructures, including spheres, biocontinuous structures and lamellar films. Such soft structures may find wide applications in foods, agriculture, and biomedical engineering. A phase diagram was built to identify the experimental conditions leading to the formation of various mesophases. Boundary lines were fitted with models derived from Flory-Huggins solution theory. Microstructure was investigated by SEM, FIB, TEM, and FTIR.

 

Title:
The Outlook for Energy: A View to 2030
Speaker:Rob Gardner
Date:11 April 2011 
Time:2.00pm to 3.00pm
Venue:NTU SPMS Lecture Theatre 3, Level 3 
Host:Associate Professor Roderick W. Bates
Abstract:

The world faces tremendous energy challenges. Energy enables economic growth and plays a key role in advancing social progress. Over the next two decades, demand for energy is forecast to rise dramatically across the globe, as populations and economies grow. Meeting the growing need for reliable and affordable energy - safely and with minimal environmental impact - is a key challenge facing governments and societies worldwide. Success will require international cooperation and a tremendous investment in new technologies to enable the world to expand its energy choices, improve efficiency and reduce emissions.

Key topics to be covered:

•   Energy supply/demand outlook to 2030
•   Trends and new developments in world oil and gas supply
•   Availability of energy sources, including fossil fuels, nuclear power and renewable energy
•   Electricity demand growth and implications for power generation
•   The growing role of natural gas in the energy mix
•   Energy-related CO2 emissions to 2030

 

Title:
Recent Progress in Catalyzed Addition Reactions of H-P(O) Compounds to Alkynes
Speaker:Professor Masato Tanaka
Date:1 April 2011 
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor François Mathey
Abstract:

Some ten years ago an interesting regiochemical reversal induced by Ph2P(O)OH in Pd-catalyzed addition of Ph2P(O)H with terminal acetylenes was disclosed and [Ph2P(O)-Pd-OP(O)Ph2] species was proposed as key intermediate.1 During the course of addition-carbocyclization of a,w-diynes with HP(O)Ph2,2 however, we have come across unexpected result that suggests the real active species is a zwitterionic palladium complex formed though hydrogen bonding with ligated P(O)Ph2 moiety with a Ph2P(O)OH (Scheme 1).3 Detailed study has shown (1) HP(O)Ph2 is activated by palladium center through oxidative addition, (2) resulting species interacts with Ph2P(O)OH through hydrogen bonding, forming an intermediate having PPh2(O-H-OP(O)Ph2), which is a sort of phosphine ligand and prone to dissociate to generate a vacant coorination site, and (3) then an alkyne occupies the site to undergo insertion. Thus, the whole process is carried by duo of palladium and Ph2P(O)OH. This type dual activation facilitates the catalysis more efficiently as compared with the regime without Ph2P(O)OH or other Brønsted acids and has been found to successfully work in addition of dialkylphosphine oxide to alkynes (Table 1). Furthermore, similar dual activation was found with nickel and Brønsted acids and allowed the addition of dialkylphosphine oxide to take place very efficiently at room temperature.4 

Brief summary of H-P bond addition reactions and recent progress are presented.

 

Title:
Calculating, Modeling & Analyzing Molecular Vibrational Motion in Multidimensional Spectroscopy
Speaker:Professor Yoshitaka Tanimura
Date:30 March 2011 
Time:3.00pm to 4.30pm 
Venue:NTU SPMS MAS Executive Classroom 1 
Host:Assistant Professor Tan Howe Siang
Abstract:

Spectral line shapes in a condensed phase contain information from various dynamic processes that modulate the transition energy, such as microscopic dynamics, inter and intramolecular couplings, and solvent dynamics. In this talk, we explore and describe the roles of different physical phenomena that arise from the peculiarities of the system-bath coupling in multidimensional spectra.  For this purpose, we employed the Brownian oscillator model with the nonlinear system-bath interaction. Using the hierarchy formalism, we could precisely calculate multidimensional spectra for a single and multimode anharmonic system for inter- and intramolecular vibrational modes.

We examined the capability of the present approach by comparing the signals of two- and three-dimensional IR vibrational spectroscopy obtained from experiments and molecular dynamics simulations. 

 

Title:
Bioactive Response of Cultured Hepatocarcinoma Cells and Adipocytes to Triterpenoids Derived from Selective Medicinal Plants
Speaker:Assistant Professor Popovich, David Glen
Date:25 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Associate Professor Li Tianhu
Abstract:

Bioassay guided extraction has been employed to obtain bioactive compounds from a variety of plants common in traditional Chinese diet and medicine. Three different cultured cell lines derived from hepatic, intestinal carcinoma and adipose cells are used to assess the activity of extracted materials to induce apoptosis or necrosis, reduce lipid accumulation and increase adipocytokines expression, as well as to estimate bioavailability. Once bioactivity is detected and the phytochemical profile has been established by HPLC-MS analysis, the extracts are typically fractionated based on the polarity of the resultant HPLC profile. Fractions of interests are then concentrated and further tested for activity and potential additive, antagonistic synergistic response when combined with other extracts, phytochemicals or pharmaceuticals. This presentation will focus on the bioactive determination of triterpenoids recovered from medicinal plants such as American ginseng (Panax quinquefolius), Asian ginseng (Panax ginseng), soy (Glycine Max) and bitter melon (Momordica charantia). These plants have a long history of use and contain complex triterpenoid compositions that possess multiple activities such as cytotoxicity and induction of apoptotic cell death, ability to differentiate hepatocarcinoma cells, reduce lipid accumulation and increase adiponectin secretion from the adipocyte. For example, both American ginseng and Asian ginseng contain similar dammarane type triterpenoids commonly known as ginsenosides that differs in proportions. Asian ginseng however has been shown to reduce lipid accumulation and increase adiponectin secretion from the adipocytes at lower concentration than American ginseng. In addition, oleanane triterpenoids from soy have varying cytotoxicity that is dependent on chemical structure. The focus of the research is to ultimately classify bioactive response based on the chemical structure of the compound and to provide evidence-based preclinical data that would allow the development of novel products that may be used to combat metabolic-related disease such as insulin resistance.

 

Title:
Introduction to the NTU Protein Production Platform
Speaker:Assistant Professor Tobias Carl Cornvik
Date:24 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Xing Bengang
Abstract:

In 2010 a protein production platform was established as part of a structural biology effort headed by Prof Pär Nordlund. It has been available for researchers at SBS and we have to date worked with more than 20 PIs, helping them to produce their protein(s) of interest. To date we have produce approximately 500 protein batches and cloned more than 2500 constructs.

We employ a very successful multi-construct approach to increase the success rate of producing soluble proteins in E.coli and we typically achieve desired purity after a two-step purification consisting of IMAC and SEC.

The platform uses high-throughput technologies with a cloning and screening capacity of roughly 2*96 constructs per month and a large-scale purification capacity of 12 proteins per week.

We are now offering our services to other schools outside SBS and in my presentation I will describe the technologies used in the platform and how the researchers will submit their targets.

 

Title:
How Proteins Understand Genomes
Speaker:Dr Ralf Jauch
Date:23 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

Many transcription factor (TF) proteins bind short, degenerate and often indistinguishable DNA sequences suggesting that they are biochemically capable of binding a large fraction of the genome. Yet, individual TFs are functionally non-redundant or even antagonize each other and execute distinctive gene expression programs.  Thus, to achieve selectivity, combinations of TFs must team up and cooperate to specifically target genomic control regions and regulate gene expression. We seek to understand how TF cooperativity is brought about on the level of DNA recognition. To this end, we study the importance of constraint DNA motif arrangements, effects of protein binding on DNA structure as well as allosteric changes of variant DNA ligands on protein contact interfaces. By using computational, biochemical, biophysical and crystallographic methods we investigate the make-up of genomic control regions and seek to identify elements, within the bound DNA sequences as well as within the TF, that determine specificity in the process of gene regulation. I will discuss structural and functional work on the Sox, POU, Pax and Smad TF families and demonstrate how the rational re-engineering of TF cooperation can lead to dramatic functional swaps in vivo. I will also touch on our efforts to assess strategies for the targeted modulation of TF activity using small molecules.

 

Title:
Multi-scale” Simulation of Processes in Membrane Proteins and Biomembranes: Methods and Applications
Speaker:Professor Qiang Cui
Date:16 March 2011 
Time:11.00am to 12.30pm 
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Robin Chi Yonggui
Abstract:

I’ll discuss a number of topics that represent our efforts in developing reliable molecular models for describing chemical and physical processes in membrane proteins and biomembranes. This is an exciting yet challenging research area because of the multiple length and time scales that are present in the relevant problems. As an example of chemical processes in membrane proteins, I’ll discuss the problem of proton pumping, several key mechanistic questions of interest and how sophisticated QM/MM simulations can help glean new insights. As an example of problems that feature very different scales, I’ll discuss the development of coarse-grained (both particle and continuum) models that hold the promise of better understanding membrane deformations induced by amphiphiles, peptides and proteins, which are implicated in many fascinating membrane-mediate processes, such as mechanosensation, membrane translocation and membrane fusion.

 

Title:
Structure and Dynamics of Buried Interfaces of Nanopaticles, Thin Films and Biological Cells Probed by Nonlinear Light Scattering
Speaker:Professor Hai-Lung Dai
Date:15 March 2011 
Time:4.00pm to 5.00pm
Venue:NTU SPMS MAS Executive Classroom 1
Host:Professor Lee Soo Ying
Abstract:

Protein-protein interactions (PPIs) play a critical role in signaling networks that regulate numerous biological processes, such as proliferation, differentiation, and apoptosis. Low-molecular-weight inhibitors for PPIs are highly desirable due to their potential for application in pharmacology, however, disrupting such interactions by "drug-like" small molecules remains a difficult challenge because of the large and flat interfaces involved in PPIs.  Our strategy in developing synthetic organic agents for disrupting PPIs is based on the module assembly approach, where relatively small module compounds are designed to bind to a local protein surface area, and are assembled by various means, for example by covalent linking, to create a multivalent agent that is more capable of surface recognition than each individual compound.  In this presentation, the details of a proof-of-concept study on protein prenyltransferase inhibitors will be discussed. The inhibitors designed through the module assembly significantly disrupted the PPI, and showed dual inhibition potency for the enzymes sharing a common surface structure. 

 

Title:
Assembling Small Molecules for Disrupting and Detecting Protein-Protein Interactions
Speaker:Associate Professor Junko Ohkanda
Date:9 March 2011 
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

Protein-protein interactions (PPIs) play a critical role in signaling networks that regulate numerous biological processes, such as proliferation, differentiation, and apoptosis. Low-molecular-weight inhibitors for PPIs are highly desirable due to their potential for application in pharmacology, however, disrupting such interactions by "drug-like" small molecules remains a difficult challenge because of the large and flat interfaces involved in PPIs.  Our strategy in developing synthetic organic agents for disrupting PPIs is based on the module assembly approach, where relatively small module compounds are designed to bind to a local protein surface area, and are assembled by various means, for example by covalent linking, to create a multivalent agent that is more capable of surface recognition than each individual compound.  In this presentation, the details of a proof-of-concept study on protein prenyltransferase inhibitors will be discussed. The inhibitors designed through the module assembly significantly disrupted the PPI, and showed dual inhibition potency for the enzymes sharing a common surface structure. 

 

Title:
Mode of Action and Possible Real Producers of the Marine Natural Product Norzoanthamine, A Promising Candidate for Osteoporosis
Speaker:Assistant Professor Seketsu Fukuzawa
Date:3 March 2011 
Time:2.00pm – 3.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Koichi Narasaka
Abstract:

Norzoanthamine, isolated from the colonial zoanthid Zoanthus sp. has been known to suppress the decrease in femoral weight and bone biomechanical parameters caused by ovariectomy. The results of cell response assays against murine mesenchymal stem cells suggested that norzoanthamine does not affect osteoblastic differentiation, because there was no change in the alkaline phosphatase activity, while the total collagen increased in a long-term cell culture. This phenomenon is apparently caused by the suppression of collagen degradation, rather than the acceleration of collagen production. Furthermore, norzoanthamine significantly accelerates the formation of the collagen-hydroxyapatite composite, an elemental structure of bone tissue. We found that more collagen hydroxyapatite composite was formed when more collagen was present, and this represents a significant mode of action for norzoanthamine. Therefore we hypothesize that the reported bone mechanical strength enhancement is caused by collagen-norzoanthamine supramolecular association. The facts that norzoanthamine is nontoxic and that it has a collagen protective activity indicate that it may provide significant therapeutic benefits. In particular, it may be a promising drug candidate for osteoporosis treatment and prevention.

Since Zoanthus sp. is a boneless cnidarian, the described above functions are directly irrelevant to the host animal. A significant point is that norzoanthamine did not inhibit protease activity, but rather, it protected the substract proteins from proteolytic cleavage. This protective effect is more pronounced in substrates with a longer peptide chain length, and thus it exhibits a kind of cluster effect. The marine invertebrate, Zoanthus sp. is found in tropical coral reefs. These organisms are exposed to external stresses, such as UV light in intense sunshine. Norzoanthamine could protect skeletal proteins in the host animal bodies from external stresses and possibly enhance survival. Although thousands of natural products have been isolated from marine organisms, there are few compounds that resemble norzoanthamine either structurally or functionally. In the course of our effort to clarify the biological function of norzoanthamine by investigating its distribution within the animal using MALDI imaging mass spectrometry, a fungus was isolated as the predominant symbiont of the zoanthid, and production of norzoanthamine by its laboratory culture was confirmed by mass spectroscopic analyses. 

 

Title:
Coarse-Grained Force Field Simulations for Protein Structure Prediction and Protein Aggregation Dynamics and Thermodynamics
Speaker:Professor Philippe Derreumaux
Date:28 February 2011 
Time:2.00pm – 3.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Zhang Dawei
Abstract:

A very large number of small monomeric proteins adopt well-defined structures in aqueous solution. Accurate and rapid structural prediction of wild-type sequences and variants is of high interest in protein engineering.

There is, however, a class of peptides that can self-assembly and eventually form amyloid plaques. We would like by experimental and computational means to characterize all the early events preceeding nucleation at an atomic level of detail, as some of these intermediates are believed to be the main culprits in Alzheimer's disease. Thus far, this has not been possible.

In this talk, I present recent greedy approaches as well as replica exchange and standard molecular dynamics simulations of amyloid and non-amyloid peptides using both all-atom and coarse-grained protein force fields. 

 

Title:
Label-Free Biophotonic Arrays for Profiling the Blood Proteome: Allergy and the Immune Response
Speaker:Associate Professor Andrew M. Shaw
Date:15 February 2011 
Time:10.30am – 12.00pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Roderick W. Bates
Abstract:

A novel gold nanoparticle array detection technology has been developed utilising the particle plasmon as a label-free sensor for detecting target proteins in complex fluids such as blood. Seed nanoparticles are printed into an array configuration with over 10,000 spots if required and then developed into nanoparticles plasmon biophotonic sensors. Functionalising the array elements with antibodies or antigens enables binding for specific proteins to be monitored in real-time. Exploitation of the near-field properties of the particle plasmon produces an immune-kinetic assay for the determination of target protein concentrations with sensitivities to compete with ELISA assays. We are developing applications in the field of allergy including discrimination between IgE, IgG allergic responses, pointing towards a diagnosis of allergy and intolerance. Further, we have preliminary data from immune system profiling during the time course of patient recovery post large scale surgery. 

 

Title:
Rational Design of Self-Assembled Nanoparticles for Ultra-Sensitive SERS Sensing
Speaker:Dr Xing-Yi Ling
Date:10 February 2011 
Time:2.00pm – 3.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Shao Fangwei
Abstract:

Plasmonic structures are optimal platforms for ultra-sensitive Surfaced-Enhanced Raman Spectroscopy (SERS) sensing. Here,  we demonstrate a systematic means of reproducing stable and sensitive plasmonic nanostructures with high SERS enhancement factor. Our strategy involves the synthesis of highly uniform shaped-controlled Ag nanocrystals; and large scale oriented self-assembly of these individual Ag nanoparticles into pre-defined (patterned) substrate to form well-defined and discrete plasmonic nanostructures. We studied the size and morphology of faceted Ag nanoparticles to the optimal localized surface plasmon resonance and Raman enhancements. We also extend our SERS study for environmental sensing of Arsenic compound, with detection limits as low as 0.1ppb. Such ultra-sensitive SERS platform is an attractive and practical tool for more sensitive, portable and disposable sensing.

 

Title:
Tales of the Unexpected: Serendipity in Natural Product Synthesis
Speaker:Professor Richard J. K. Taylor
Date:8 February 2011 
Time:3.30pm – 5.00pm
Venue:NTU SPMS Lecture Theatre 4
Host:Assistant Professor Roderick W. Bates
Abstract:

The lecture will introduce recent research directed towards the total synthesis of bioactive natural products such as the Oxazolomycins, the Dictyosphaeric Acids, the Daphnezomines and the Grandisines (see below). However, the lecture will be concerned mainly with unexpected results obtained during these natural product studies and how these have generated new areas of research

 

Title:
Lipopolysaccharide assembly in Gram-negative bacteria
Speaker:Dr Chng Shu Sin
Date:8 February 2011 
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract:

Lipopolysaccharide (LPS) is a glycolipid found exclusively in the outer leaflet of the asymmetric outer membrane of Gram-negative bacteria.  Proper placement of LPS at this location is essential for cell viability; thus inhibitors of this pathway could represent useful antibiotics.  In Escherichia coli, eight essential proteins have been identified to function in LPS assembly following its biosynthesis.  This assembly process involves release of the glycolipid from the inner membrane, transport across the aqueous periplasm, and insertion into the outer leaflet of the outer membrane.  In this seminar, I will talk about our work in characterizing the LPS assembly machinery and discuss the mechanisms of LPS transport across the periplasm and its final insertion into the outer membrane.

 

Title:
Rh-Catalyzed [(5+2)+1], [7+1], [3+2], and [(3+2)+1] Cycloadditions
Speaker:Professor Yu Zhi-Xiang
Date:28 January 2011
Time:10.45am – 12.15pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract:

Discovering and developing transition metal catalyzed [m+n], [m+n+o], [m+n+o+x] cycloadditions to reach various cyclic compounds are important for the “ideal synthesis” of functional molecules, which usually have various-sized ring skeletons that are not easy or difficult to be accessed by the traditional organic reactions. Recently we developed several rhodium catalyzed cycloaddition reactions of vinylcyclopropanes with alkynes, alkenes, allenes, and CO to construct five-, six-, and eight-membered carbocycles with the aid of calculations (see these [(5+2)+1], [7+1], [3+2], and [(3+2)+1] cycloadditions in the scheme below). Some of these reactions have been applied to the synthesis of natural products to demonstrate the impacts of these cycloaddition reactions on synthesis. 

 

Title:
Effect of Highly Fluorinated Amino Acids on Secondary Structure Stability
Speaker:Professor Richard Cheng
Date:26 January 2011
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Assistant Professor Brendan Orner
Abstract:

Highly fluorinated amino acids have been used to stabilize helical proteins, with limited studies on sheet-containing proteins. Here we will present the effect of these highly fluorinated amino acids on two protein secondary structures: alpha-helix and beta-sheet. Furthermore, we will present a three-step chemoenzymatic stereoselective gram-scale synthesis of fluorinated leucines. We will also show the effect of introducing fluorines on the hydrophobicity of the amino acids. The helix propensity was measured using Ala-based peptides, whereas the effect on beta-sheet stability was measured using protein G B1 domain (GB1). Various amino acids were studied including 5,5,5,5’,5’,5’-hexafluroleucine, 5,5,5’,5’-tetrafluoroleucine, pentafluorophenylalanine, leucine, phenylalanine, and alanine. The peptides and proteins were synthesized by solid phase peptide synthesis. The hydrophobicity of the amino acids were measured by thin layer chromatography under neutral and acidic conditions. The Rf values were used to derive the logarithm of the partition coefficient (logP) as a gauge for hydrophobicity. The circular dichroism spectra of the Ala-based peptides were used to derive the helix propensity. Thermal denaturation of GB1 derivatives were monitored by circular dichroism spectroscopy and used to explore the effect on sheet stability. In general, complete fluorination of the methyl or phenyl groups resulted in increase in hydrophobicity; partial fluorination of these groups led to decrease in hydrophobicity. Helix propensity decreased significantly upon fluorination. In contrast, sheet stability increased upon introducing the fluorines. Therefore, highly fluorinated amino acids may be more suitable for stabilizing beta-sheets in sheet-containing proteins compared to helical proteins.

 

Title:
Catalytic Reactions Involving Activation of Unreactive Bonds
Speaker:Professor Naoto Chatani
Date:25 January 2011
Time:10.45am – 12.15pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract:

We reported some results for a series of Ru- and Rh-catalyzed carbonylation reactions of C-H bonds. In all cases, the substrates required the presence of an sp2 nitrogen. This suggests that the coordination of the sp2 nitrogen to the catalyst is an important for the reaction to proceed. Our findings also showed that, in such carbonylation reactions of C-H bonds, both high CO pressures and high reaction temperatures were required for a successful reaction. Because of this, carbonyl compounds, such as ketones, esters, and amides are not typically used in the Ru- and Rh-catalyzed C-H bond carbonylation because of their low coordination ability. The substrates must compete with the higher pressure of CO. This encouraged us to develop a new bidentate system that would be applicable to the ortho C-H bond carbonylation of aromatic amides.

We found new types of some catalytic reactions involving the cleavage of C-CN bonds in nitriles, which proceed via a silicon-assisted mechanism.  Silylation,  reductive decyanation,  intramolecular C-C bond formation,  and the Mizoroki-Heck type reaction  will be discussed.

 

Title:
Directed Assembly of C4-Symmetric Vanadate-Centered Quadruplexes: Synergistic Ion-specific Transport and Asymmetric Catalysis
Speaker:Professor Chen Chien-Tien 
Date:21 January 2011
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2, Conference Room
Host:Professor Loh Teck Peng
Abstract:

We have developed a series of N-Salicylidene-based L-a-amino acids as chiral auxiliaries for chiral vanadyl(V) methoxide complex synthesis. These configurationally well-defined complexes have been examined for kinetic resolution of 2o alcohols. They serve as efficient and highly enantioselective catalysts for asymmetric aerobic oxidation of α-hydroxy acid,  phosphonic acid, and ketone derivatives at ambient temperature. The asymmetric inductions of the oxidation process are in the range of 50 - > 500 in terms of selectivity factors (krel) in most instances. X-ray crystallographic analysis of an adduct between N-benzyl-mandelamide and the catalyst allows for probing the origin of the nearly exclusive asymmetric control in the oxidation process.

In the case of the 3,5-di-tert-butyl and 3,5-dihalo- substituted analogs, pentanuclear C4-symmetric complexes were formed when potassium salts were employed instead of the corresponding sodium salts. The complexes work synergistically in the asymmetric aerobic oxidations of various racemic a-hydroxy acid and ketone derivatives with excellent selectivity factors. A directed assembly process to form C4-symmetric, vanadate-centered helical quadruplexes, for the first time, from a given chiral oxidovanadium(V) complex allows for highly efficient K+-, Ag+, Ba2+, Pb2+, Hg2+, and (chiral) ammonium ion-specific transports from aqueous phase into organic solvents, reminiscent of the K+ specific transport exerted by four homochiral glycine residues of the opening site in KcsA membrane protein.

 

Title:
Aggregation-induced Emission: Phenomenon,Mechanism and Applications
Speaker:Professor Tang Ben Zhong
Date:17 January 2011
Time:11.00am – 12.30pm
Venue:NTU SPMS CBC Building Level 2,Conference Room
Host:Assistant Professor Chen Hongyu
Abstract:

It is textbook knowledge that chromophore aggregation generally quenches light emission. In this talk, I will give an account on how we observed an opposite phenomenon termed aggregation-induced emission (AIE) and identified the restriction of intramolecular rotation as a main cause for the AIE effect. Based on the mechanistic understanding, we developed a series of new fluorescent and phosphorescent AIE systems with emission colours covering the entire visible spectral region and luminescence quantum yields up to unity. We explored high-tech applications of the AIE luminogens as, for example, fluorescence sensors (for explosive, ion, pH, temperature, viscosity, pressure, etc.), biological probes (for protein, DNA, RNA, sugar, phospholipid, etc.), immunoassay markers, PAGE visualization agents, polarized light emitters, monitors for layer-by-layer assembly, reporters for micelle formation, multistimuli-responsive nanomaterials, and active layers in the fabrication of organic light-emitting diodes.

 

Title:
Magic Nano-bullets and the Mace Head Effect for New Drug Development
Speaker:Professor Hwu Jih-Ru
Date:13 January 2011
Time:2.00pm to 3.30pm 
Venue:NTU SPMS CBC Building Level 2,Conference Room
Host:Assistant Professor Xing Bengang