Inaugural GSK-Singapore Partnership for Green and ... GSK-Singapore Partnership for Green and...

Inaugural GSK-Singapore Partnership for Green and Sustainable Manufacturing Symposium 2011 6th July 2011 – 7th July 2011

THE INAUGURAL

GSK-SINGAPORE PARTNERSHIP

FOR

GREEN AND SUSTAINABLE

MANUFACTURING SYMPOSIUM 2011

Symposium Proceedings


CONTENTS

Opening address

- GlaxoSmithKline

- Singapore Economic Development Board

Layout plan Section 1

Day 1 Symposium Programme Section 2

Day 2 Symposium Programme Section 3

Evaluation form Section 4


WEDNESDAY

6 JULY

MORNING AFTERNOON EVENING - Registration - Opening

Updates on 2011 proposals

Poster Session GSM Fund Award Ceremony

Invited Lecture

Keynote Speech


Invited Lecture Invited Lecture

THURSDAY

7 JULY

MORNING AFTERNOON EVENING - Welcome - Summary of Day 1

Invited Lecture

Keynote Speech 2



Invited Lecture

Symposium Closing

Agenda-at-a-Glance


[Divider labelled ‘Layout Plan’]


GSM SYMPOSIUM 2011 POSTER LAYOUT PLAN

No. Poster Title Author(s) Affiliation

1 Control and optimization strategy for real-time product quality assurance and energy efficiency in batch manufacturing process

David Wang ICES

2 Rapid Emulsification in Microfluidics Claus-Dieter Ohl NTU

3 Copper Catalyzed Carboxylation of Alkynes with CO2 Yugen Zhang and Dingyi Yu IBN

4 Artificial Neural Network-based Drug Design for Complex Diseases Jagdish C. Patra NTU

5 Triple Bottom Line Sustainability Analysis of Fine Chemicals Manufacturing and Supply Chain

Arief Adhitya ICES

6 Commodity Chemical Production in Hetero- and Photo-trophic Microbes

Kinya Hotta NUS

7 Enzymatic synthesis of c-di-GMP using a thermophilic diguanylate Cyclase

Swathi Pasunooti NTU

8 A Knowledge-Based Framework for Sustainable Batch Chemical Manufacturing Processes

Iskandar Halim ICES

9 A Methodology for Integrated Optimization of Scheduling, Energy and Water Usage in Batch Chemical Processes

Iskandar Halim ICES

10 High-yield Xylitol Bioproduction by a New Isolate Candida Sp. SB18

Dr. Geng Anli NP

11 Ionic Liquid Stabilized Pd(0) Nanoparticles for Aminocarbonylation of Aryl Halides

Yinghuai Zhu ICES


12 Investigation of in-situ Physical Transformation of a Lipohilic Drug Formulation under Simulated Stomach Condition.

G. Roshan Deen NTU

13 Achieving manufacturing sustainability in pharmaceutical companies through optimal resource planning and inventory management

Naresh Susarla and I. A. Karimi

NUS

14 Green Initiatives for SWAMI Lim Shin Yi and Goh Sian Meng

RP

15 Siliceous Mesocellular Foam (MCF) Supported Catalysts for Green and Sustainable Manufacturing

Jaehong Lim IBN

16 Characterization and Optimization of Solid Lipid Nanoparticle Carrier Systems for Delivery of Anti-Fungal Agents

Surajit Das, Wai Kiong Ng and Reginald B. H. Tan

ICES

17 Characterisation Framework Development for the Proposed SIMPASS (Singapore IMPact ASSessment) Methodology

Yin T. Chan, Reginald B.H. Tan and

Hsien H. Khoo ICES

18 Enhancing Bioavailability of Poorly Aqueous Soluble Drugs through Formulating Amorphous API with Porous Biocompatible Excipient.

Kumaran Letchmanan, Shou-Cang Shen, Wai Kiong Ng and

Reginald Beng Hee Tan

NUS & ICES

19 Development of melt extruded floating controlled delivery system for clarithromycin

Parijat Kanaujia, Surajit Das,

Wai Kiong Ng and Reginald B H Tan

ICES & NUS

20 Viscosity Reduction of An Ionic Liquid through Addition of Carbon Nanotubes and its application in Dye-sensitized Solar Cells

Chin Yong Neo and Jianyong Ouyang

NUS

21 Continuous Processing for Sustainable Manufacturing of β‐Hydroxy Ester via Reformatsky Reaction

Gabriel Loh ICES

22 Green Manufacturing of Nanoparticles: A Biological Approach Sierin Lim NTU

23 Continuous processing for sustainable manufacture of fine chemicals and Active pharmaceutical ingredients

Loretta Wong ICES

24 Dinuclear and Tetranuclear Pd(II) Complexes of a Thiolato-functionalized, Benzannulated N-Heterocyclic Carbene Ligand and their Activities towards Suzuki-Miyaura Coupling

Dan Yuan and Han Vinh Huynh

NUS

25 Copper-Catalyzed Oxidative Amidation of Aldehydes with Amine Hydrochloride salts

Subhash Chandra Ghosh, Anqi Chen,

Joyce Ngiam Shi Yun and

Christina L. L. Chai

ICES

26 A composite protonated titanate/ titania photocatalyst for effective visible light degradation of phenol

Yu Hua Cheng (Gloria) and Zhong Chen

NTU

27 Oxide nanostructures as a super-adsorbent for depollution and chemical recovery

Yuxin Tang, Zhili Dong and

Zhong Chen NTU

28 Immobilization of Lipase on Hydrophobically Modified Nanoporous Silica Under High Flow Conditions

Su Seong Lee IBN

29 Reducing Excess Production of the Active Pharmaceutical Ingredient during Early-Phase Development

Kan Wu, Rajesh Piplani NTU

30 Direct Arylation of Perfluoroaromatics with Aryl Trifluoromethanesulfonates

Joyce Wei Wei Chang, Eugene Yurong Chia,

Christina Li Lin Chai and Jayasree Seayad

ICES

31 Design A Reverse Logistics Information System With RFID CKM Lee NTU

32 Using Second Virial Coefficients to Guide Development of Rational Protein Refolding Processes

Anindya Basu and Susanna Su Jan Leong

NTU

33 An Environmentally Attractive Amide Synthesis using Supported Palladium Nanoparticles Catalyzed Aminocarbonylation

Tuan T. Dang, Zhu Yinghuai,

Chen Anqi, Christina L. L. Chai and

Abdul M. Seayad

ICES


[Divider labelled ‘Day 1’]


Day 1 – Wednesday, 6 July 2011 (Morning)

Green & Sustainable Manufacturing Symposium

Chairperson for morning session: Dr. Paul Sharratt Programme Manager (Process Science and Modeling) Institute of Chemical & Engineering Sciences (ICES) Agency for Science, Technology and Research (A*STAR)

9:00-9:30

Registration / Coffee

9:30-9:45

Welcome by Dr. Paul Sharratt

9:45-10:00

OPENING ADDRESS Mr. Chris Dobson Vice-President & Site Director Global Manufacturing & Supply Singapore, GlaxoSmithKline

10:00-10:45

THE GSK-SINGAPORE PARTNERSHIP FOR GREEN AND SUSTAINABLE MANUFACTURING FUNDING AWARD CEREMONY Awards Presenter: Dr. Philip C. Dell’Orco Head, Particle Generation, Control, and Engineering Head, Manufacturing Sustainability Platform Technology and Sciences, R&D GlaxoSmithKline

10:45-11:15

KEYNOTE ADDRESS “Sustainability: Staying Ahead of the Curve” Mr. Andrew Tan Chief Executive Officer National Environment Agency, Singapore


11:15-12:00

INVITED LECTURE “Global Green Chemistry Landscape – What is Next?” Prof. Chao Jun Li E.B. Eddy Chair Professor of Chemistry and Canada Research Chair (Tier I) in Green Chemistry McGill University

12:00-13:00

LUNCH

13:00-13:30

GSM PROPOSAL UPDATE “Environmentally Benign Amide Formation Reactions” Dr. Anqi Chen Senior Scientist Institute of Chemical and Engineering Sciences, A*STAR, Singapore

13:30-14:00

GSM PROPOSAL UPDATE “Green Organic Catalysis and Synthesis” Prof. Robin Chi Assistant Professor Nanyang Technological University


Day 1 – Wednesday, 6 July 2011 (Afternoon)


Chair for afternoon session: Dr. Verner De Biasi Scinovo Chemical Development Director GlaxoSmithKline

14:00-14:45

INVITED LECTURE “Continuous Processing and Surface-Induced Crystallization for Greener Pharmaceutical Production” Prof. T. Alan Hatton Ralph Landau Professor & Director, David H. Koch School of Chemical Engineering Practice, Massachusetts Institute of Technology

14:45-15:15

GSM PROPOSAL UPDATE “Green Chemical Synthesis via Biocatalysis: Discovery and Engineering of Novel Biocatalysts for Regio- and Stereo-Selective Biohydroxylations” Prof. Zhi Li Associate Professor Department of Chemical & Biomolecular Engineering National University of Singapore

15:15-15:45

TEA BREAK

15:45-16:10

GSM PROPOSAL UPDATE “Symbiotic Hollow Fiber Membrane Photobioreactor for Microalgae Growth and Activated Sludge Waste Water Treatment” Prof. Kai Chee Loh Associate Professor & Deputy Head (Research) Department of Chemical & Biomolecular Engineering National University of Singapore


16:10-16:30

GSM PROPOSAL UPDATE “Using Protein Immobilized Membranes for Water Purification and Treatment” Prof. Yen Wah Tong Associate Professor Department of Chemical and Biomolecular Engineering Division of Bioengineering National University of Singapore

16:30-17:15

INVITED LECTURE “Scalable Processes to Pharmaceutical Intermediates and APIs using Evolved Enzymes” Prof. Steve Collier Director of R&D and General Manager Codexis

17:15-19:00

POSTER SESSION / RECEPTION / NETWORKING

End of Day 1 of the GSM Symposium


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OPENING MESSAGE

– GLAXOSMITHKLINE

On behalf of GlaxoSmithkline (GSK) and the Singapore Economic Development Board (EDB) I

should like to welcome you to the first symposium sponsored by our Green and Sustainable

Manufacturing (GSM) fund. The funding of S$33m is directed towards improving the

capabilities within Singapore for sustainable manufacturing, particularly in the

pharmaceuticals and fine chemicals sectors where significant improvement opportunities

exist.

GlaxoSmithKline has a strong commitment to manufacturing operations here in Singapore

and so the partnership is one example of the ways in which we can collaborate with the

Singapore community to identify opportunities for moving those operations forward in a

more sustainable way. At our Pioneer Sector factory we have a great history in energy

management and we are about to invest in significant improvements in waste management

and solvent recovery to ensure we are more capable of dealing with various waste streams

as our portfolio changes. However these changes are really associated with applying the

best end-of-pipe and recycling technologies but do not really deal with the issues at source.

We hope that through the GSM fund we can promote research into more sustainable

synthetic routes to future products such that those syntheses are greener by design and

thus generate lower environmental burdens. Whilst I hope GSK will gain some future benefit

through access to such improvements, any intellectual property generated through the fund

will belong to the local institutions. This is with the objective of encouraging implementation

of improvements industry-wide thus benefiting all of Singapore and the environment as a

whole.

I am also delighted that we have with us for the symposium, members of the fund’s

Scientific Advisory Board and GSK colleagues from other parts of the world, giving an

international dimension to our proceedings.

Thank you to the distinguished speakers who are supporting our symposium, to all of the

researchers working on funded projects, to those who are presenting posters and to all of

the participants. I hope this will be the first of many such symposia and that our efforts will

inspire others to join our commitment to a sustainable future.

Chris Dobson Vice-President & Site Director Global Manufacturing & Supply GlaxoSmithKline, Singapore


OPENING MESSAGE

– SINGAPORE ECONOMIC DEVELOPMENT BOARD

I would like to extend a warm welcome to all participants of the inaugural GSK-Singapore

Green & Sustainable Manufacturing Partnership Symposium. It brings me great pleasure

that, in the course of a strong 52-year partnership between GlaxoSmithKline and Singapore,

I am able to share this occasion with you.

In the 21st century, the healthcare industry is looking not just at pure social and economic

impact, but towards greater environmental stewardship. The co-investment with GSK will

continue to build on Singapore’s strong scientific fundamentals to develop new green and

sustainable manufacturing capabilities. I believe this long-term effort will help us push the

frontiers of pharmaceutical and fine chemicals manufacturing. Innovation will allow us to

adopt more environmentally sustainable production processes and help bring affordable

medicines to the world.

I would like to extend my appreciation to the National Environment Agency’s CEO Mr

Andrew Tan, the Scientific Advisory Board members who have flown in to attend the event,

the Industry Advisory Group, our GSK partners and, last but not least, our community of

industry and scientific partners without whom this would not have been possible. With the

exciting presentations, posters and awards ahead of us, I wish you a rewarding session at

the 2011 GSK-Singapore Partnership for Green & Sustainable Manufacturing symposium.

Beh Kian Teik

Director, Biomedical Sciences

Singapore Economic Development Board


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KEYNOTE ADDRESS:

“Sustainability: Staying Ahead of the Curve”

Mr Tan Kok Kiong Andrew was appointed Chief Executive Officer of National Environment Agency (NEA) on 1 January 2009. As CEO/NEA, he is responsible for ensuring that Singapore achieves high standards of environmental sustainability in the areas of clean air, land and water. He is also responsible for pollution control, public hygiene standards, resource conservation, sustainable waste management and meteorological services.

Mr Tan joined the Singapore Administrative Service in 1991. He has worked in the Ministry

of Information and the Arts, Ministry of Defence, Ministry of Foreign Affairs and Ministry of

The Environment and Water Resources. He was also Principal Private Secretary to the

former Minister Mentor Lee Kuan Yew. He was Founding Director of the Centre for Liveable

Cities from 2008 to 2010 and remains as a Fellow.

Mr Tan graduated with a First Class Honours Degree in History from King's College,

University of London, in 1989. He attended the Edward S Mason Programme at the Harvard

Kennedy School of Government, where he obtained his Masters in Public Administration in

2002.

Mr Tan is a Member of the Agency for Science, Technology and Research (A*STAR) Board

and the Energy Studies Institute Management Board.

Presentation Abstract:

The world is now more interdependent and integrated than ever. Population growth, rapid

urbanisation and industrialisation and a growing demand for resources has led to our

society facing several tipping points - threats of climate change, pollution and

environmental degradation to name a few. Our future depends on how we are able to

respond to a more complex environment. In the face of these challenges, organisations and

governments need to integrate sustainability into their core strategies and leverage on

scientific research to tackle the crises that confront them.

Andrew Tan

Chief Executive Officer

National Environment Agency, Singapore


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INVITED LECTURE:

“Global green chemistry landscape – What is next?”

Chao-Jun Li (born in 1963) received his B.Sc. at Zhengzhou University (1983), MS at the

Chinese Academy of Sciences in Beijing (1988) and Ph.D. (with honors) at McGill University

(1992) under the direction of T. H. Chan and D. N. Harpp.

He spent 1992-94 as a NSERC Postdoctoral Fellow with Barry M. Trost at Stanford University

(US), and was an Assistant Professor (1994), Associate Professor (1998) and Full Professor

(2000) at Tulane University (US). Since 2003, he has been a Canada Research Chair (Tier I) in

Green Chemistry and a Professor (E. B. Eddy Chair Professor since 2010) of Organic

Chemistry at McGill University in Montreal, Canada.

Currently, he serves as the Co-Chair of the Canadian Green Chemistry and Engineering

Network, the Director of the CFI Facility for Green Chemistry and Green Chemicals, and the

Co-Director of the FQRNT Center for Green Chemistry and Catalysis. He also serves as the

Associate Editor for the Americas for the journal of Green Chemistry (RSC), and a consulting

editor for McGraw-Hill’s Encyclopedia of Sciences and Technologies and McGraw-Hill’s Year

Book of Sciences and Technologies.

He received a number of prestigious awards/honors worldwide. These include the National

Science Foundation’s CAREER Award (1997), an outstanding young Chinese Scientist Award

(overseas) by the Chinese National Science Foundation (2000), a Presidential Green

Chemistry Challenge Award by the US EPA (2001), and a Canadian Green Chemistry and

Engineering Award (2010). He was a Japan Society for the Promotion of Science (Senior)

Fellow in 2002. He was elected as a Fellow of the Royal Society of Chemistry (UK, 2007).

His current research efforts are to develop Green Chemistry for organic synthesis based

upon innovative and fundamentally new organic reactions that will defy conventional

reactivities and possess high “atom-efficiency”. Well-known research developed by his

group include the development of a wide range of Grignard-type reactions in water,

transition-metal catalysis in air and water, alkyne-aldehyde-amine coupling (A3-coupling),

Chao Jun Li

E.B. Eddy Chair Professor of Chemistry

Canada Research Chair (Tier I) in Green Chemistry

McGill University


and cross-dehydrogenative-coupling (CDC) reactions among others. His work has been cited

extensively (>11,000 times, h-index=56) in the literature.

In 2007, his research was listed as “one of the 20 most important chemistry discoveries of

the past century in Canada”. He authored (together with T. H. Chan) the popular book

“Organic Reactions in Aqueous Media” (John Wiley, 1997) and the “Comprehensive Organic

Reactions in Aqueous Media” (John Wiley, 2007), and edited two volumes of the Handbook

of Green Chemistry Series: “Green Solvents” and Green Syntheses”. He has published ca 300

research papers and has given over 230 plenary and invited lectures worldwide.


The efficient making of new molecules is central to any new product in the pharmaceutical,

materials science, microelectronics, and biotech industries. On the other hand, chemical

manufacturing and chemical products have also affected us adversely from personal, local,

national, and international scales.

As a new philosophy over the last two decades, Green Chemistry though the 12 principles of

green chemistry has emerged to develop the next generation of chemical science and

technologies, as well as chemical products to meet such challenges in a proactive manner

both environmentally and economically.

During the past two decades, atom-economy, react mass efficiency, and E-factor have

allowed us to evaluate green chemical processes. The use of greener solvents provides

another important factor in designing greener processes.

What’s next? In this talk, we will discuss potential development of this field from the PI’s

perspective and present some research in the PI’s laboratory.


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UPDATES ON GSM 2010 PROPOSALS:

“Progress in Environmentally Benign Amide Formation Reactions”

Anqi Chen

Senior Scientist Institute of Chemical and Engineering Sciences, A*STAR, Singapore

Dr Anqi Chen received his PhD degree in organic synthesis from Bristol University, UK in

1992. After a period of postdoctoral research at Manchester University on total synthesis of

natural products, he took up an academic position at Xiamen University, China in 1997. He

joined the Institute of Chemical and Engineering Sciences (ICES), A*STAR in 2004 and is

currently a Senior Scientist and team leader in the Organic Chemistry Programme.

His major research interests are in the development of green and sustainable technologies

for chemical synthesis, process chemistry for pharmaceuticals and fine chemicals, synthesis

of bioactive molecules for drug discovery. He is a member, Chartered Chemist of the Royal

Society of Chemistry, UK and a Chartered Scientist of the Science Council, UK.


Amide bond formation is one of the most often used transformations in the synthesis of

pharmaceutical compounds and fine chemicals. As a result, a plethora of methods for amide

formation reactions have been developed.1 However, most of these existing methods have

several common drawbacks, such as poor atom-efficiency, use of hazardous reagents, and

generation of wastes that not only reduce process efficiency but also pose environmental

problems. Consequently, amide formation has been identified by the pharmaceutical

industry as one the reactions that most need improving.2 This presentation will highlight

recent progress in environmentally benign amide formation reactions and their potential

applications in pharmaceutical and fine chemical industries.

References:

1. (a) Montalbetti, C. A. G. N.; Falque V. Tetrahedron, 2005, 61, 10827. (b) Valeur, E.; Bradley, M. Chem. Soc.

Rev. 2009, 38, 606. (c) Allen, C. L.; Williams, J. M. J. Chem. Soc. Rev. 2011, DOI: 10.1039/c0cs00196a.

2. Constable, D.; Dunn, P.; Hayler, J.; Humphrey, G. Leazer, Jr., J.; Linderman, R.; Lorenz, K. Manley, J.;

Pearlman, B.; Wells, A; Zaks, A.; Zhang T. Green Chem. 2007, 9, 411.


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“Green Organic Catalysis and Synthesis”

Robin Chi

Assistant Professor

Nanyang Technological University

Prof. Robin (Yonggui) Chi started his group at Nanyang Technological University in 2009

under Singapore’s initiative in recruiting talented young professors. He is currently an

Assistant Professor at NTU and a Singapore National Research Foundation Fellow. His

group’s research involves the development of catalysis and catalytic synthesis with

applications that reaches pharmaceuticals, peptides, proteins, and materials. Previously,

Robin received his undergraduate training at Tsinghua Univ. and Hong Kong Baptist Univ.

(1998-2002), PhD at UW-Madison (with Sam Gellman, 2002-2007), and Post-doctorate at

UC-Berkeley (with Jean Frechet, 2007-2009).


Despite the tremendous advancements in organic synthesis, most of today’s organic

transformations are not effective enough for clean and sustainable synthesis. Here we’ll

present our efforts in developing organic catalysis (organocatalysis) for the rapid assembly

of sophisticated molecules and atom-economic synthesis of widely-used functional

molecules. Examples of specific directions to be discussed include catalysis N-Hetereocyclic

Carbene, amine, imiunum, and acid catalysts.


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INVITED LECTURE:

“Continuous Processing and Surface-Induced Crystallization for

Greener Pharmaceutical Production”

T. Alan Hatton is the Ralph Landau Professor and Director of the David H. Koch School of

Chemical Engineering Practice at the Massachusetts Institute of Technology. He obtained

his BSc and MSc degrees in Chemical Engineering at the University of Natal, Durban, South

Africa, and worked at the Council for Scientific and Industrial Research in Pretoria for three

years before attending the University of Wisconsin, Madison, to obtain his PhD.

His research interests encompass self-assembly of surfactants and block copolymers,

synthesis and functionalization of magnetic Nan particles and metal-organic frameworks for

chemical, biological and environmental separations and catalysis, and the exploitation of

stimuli-responsive materials for chemical and pharmaceutical processing applications, with

a particular current emphasis on electrochemically-mediated operations.


Traditional pharmaceutical formulations rely heavily on the manipulation of powders during

batch milling, blending and granulation operations, all of which can lead to powder losses,

unsafe working environments, and unnecessary expenditure of energy. These operations

can be streamlined by operating in a continuous mode, and by introducing new processing

concepts to minimize the traditional problems associated with powder handling.

We will discuss these 'greening' concepts in general, and then focus on our recent work on

exploiting particle-induced nucleation and crystallization for the efficient processing of

pharmaceuticals. Specific examples will be given on the effects of polymer surface

chemistry and morphology on the kinetics of nucleation of model APIs on different

polymeric particles and surfaces.

This work provides new insight into surface-induced crystallization, which could potentially

be applied to the ‘greening’ of many areas of science and technology from designing ‘seed’

particles for regulating crystallization of various fine chemicals, to controlling

pharmaceutical polymorphism, orienting biominerals on organic substrates, promoting

protein nucleation for structure determination and enabling multifunctional pharmaceutical

excipient and drug-delivery vehicles.

T. Alan Hatton

Ralph Landau Professor & Director

David H. Koch School of Chemical Engineering Practice,

Massachusetts Institute of Technology


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“Green chemical synthesis via biocatalysis:

Discovery and engineering of novel biocatalysts for regio- and stereo-selective biohydroxylations”

Zhi Li

Associate Professor

Department of Chemical & Biomolecular Engineering, National University of Singapore

Professor Li Zhi received his Ph.D. in Organic Chemistry at the University of Vienna, Austria in 1991. After a year of postdoctoral research at University of Oslo, Norway, he moved to ETH Zurich, Switzerland, working as a post-doc in Organic Chemistry before becoming a scientist specialising in Polymer Chemistry and Biocatalysis. He was promoted to a group leader at the ETH Institute of Biotechnology in 1999. Since 2006, he has been an associate Professor at Department of Chemical & Biomolecular Engineering, National University of Singapore. He is a fellow of Singapore-MIT Alliance (SMA) in the program of Chemical and Pharmaceutical Engineering.

Research fields of Prof. Li include biotransformation for green and sustainable chemical and

pharmaceutical manufacturing, polymeric materials for biomedical application, and bio-

based chemical and fuel production.


Presentation Abstract: Regio- and stereo-selective biohydroxylations are important reactions for the synthesis of

enantiopure alcohols that are useful synthons, aroma materials, and pharmaceutical

intermediates. A key challenge for the practical application of this type of green transformation

(with non-toxic catalysts and molecular oxygen as oxidant) in chemical synthesis is the

development of efficient biocatalysts. We recently identified Cellulosimicrobium cellulans EB-8-4

for the allylic hydroxylation of D-limonene with >99% regio- and stereo-selectivity to give (+)-

trans-carveol, a useful and valuable fragrance and flavor compound.1 This biotransformation

afforded 42-times higher product concentration2 than the best known result. Similarly,

Pseudomonas monteilii TA-5 was developed as a powerful biocatalyst for the enantioselective

benzylic hydroxylation to give several (R)-benzylic alcohols containing reactive functional groups

in 93–99% ee as the only products with 56-66% isolated yield.3 This strain catalyzed also the

hydroxylation of indan and tetralin, giving (R)-1-indanol and (R)-1-tetralol in 99% ee and 62–67%

yields.4

We also engineered a recombinant Escherichia coli expressing the P450pyr monooxygenase from

Sphingomonas sp. HXN-200 for the regio- and stereo-selective hydroxylation.5 Biohydroxylation

of N-benzylpyrrolidin-2-one with the E. coli cells gave (S)-N-benzyl-4-hydroxypyrrolidin-2-one (a

useful intermediate for preparing oral carbapenem antibiotic CS-834) in >99% ee, with 2.6-fold

increase of product concentration in comparison with the wild type strain. The recombinant

biocatalyst demonstrated also excellent regio- and stereo-selectivity for the hydroxylation of (-)-

β-pinene giving the valuable (1R)-trans-pinocarveol in 82% yield, with 200-fold increase of the

product concentration compared with the best reported biosystem for the same

transformation.

The enantioselectivity of P450pyr monooxygenase for the biohydroxylation of N-benzyl

pyrrolidine was improved by directed evolution.6 After three generations of evolution, the best

mutant 1AF4A was able to produce the product in 83% (R) ee compared to the wild type’s 43%

ee (S). This demonstrated the first example of evolution of a P450 monooxygenase with inverted

enantioselectivity. To facilitate the evolution of enantioselective enzyme, a generally useful

high-throughput method for determining the enantioselectivity of biohydroxylations was

developed by the use of isotopically labeled enantiopure substrates and MS analysis.7 Based on

this assay and the structure information of the P450pyr hydroxylase, directed evolution led to the

discovery of a triple mutant with excellent enantioselectivity to produce (S)-N-benzyl 3-

hydroxypyrrolidine (an useful pharmaceutical intermediate) in >98% ee.8

References:

[1] Wang, Z.; Lie, F.; Lim, E.; Li, K.; Li, Z. Adv. Synth. Catal. 2009, 351, 1849 –1856.

[2] Wang, Z.; Wu, J.; Li, Z. Manuscript in preparation.

[3] Chen, Y., Lie, F.; Li. Z. Adv. Synth. Catal. 2009, 351, 2107 – 2112.

[4] Lie, F.; Chen, Y.; Wang, Z.; Li, Z. Tetrahedron: Asymmetry 2009, 20, 1206–1211.

[5] Zhang, W.; Tang, W. L.; Wang, Z.; Li, Z. Adv. Synth. Catal. 2010, 352, 3380-3390.

[6] Tang, W.; Li, Z.; Zhao, H. Chem. Commun. 2010, 46, 5461–5463.

[7] Chen, Y.; Tang W. L.; Mou, J.; Li, Z. Angew. Chem. Int. Ed. 2010, 49, 5278 –5283.

[8] Pham Q. S.; Pompidor, G.; Li, X.; Li, Z. Manuscript in preparation.


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“Symbiotic Hollow Fiber Membrane Photobioreactor for Microalgae

Growth and Activated Sludge Waste Water Treatment”

Kai Chee Loh Associate Professor & Deputy Head (Research) Department of Chemical & Biomolecular Engineering, National University of Singapore

Dr. LOH Kai Chee is an Associate Professor and Deputy Head (Research) in the Department

of Chemical & Biomolecular Engineering. Dr Loh joined the National University of Singapore

after obtaining his PhD in Biochemical Engineering from MIT. His research interests lie in

two major areas, one focusing on the biological treatment of recalcitrant aromatic

compounds, particularly in the area of co-metabolism while another in the analysis and

understanding of hydrodynamics in large‐pore matrices for bioseparations.

His latest foray in research is in the cultivation of microalgae for biolipids accumulation and

in the development of hollow fiber membrane bioreactors (HFMB) for biotransformations

applications in the pharmaceutical industry. In the former, his expertise is in the

development of hollow fiber membrane photobioreactors for enhancing microalgae growth,

as well as a study of the synergistic effect of microalgae growth with activated sludge waste

water treatment. In the latter, he is involved in using cell immobilization in HFMB to

alleviate substrate and product inhibition effects in pharmaceutical biotransformations.


Global energy crisis has motivated (re)evaluations of energy intensive activities and

processes in urban living environment, to identify areas where fossil fuel energy

dependence can be reduced by improving efficiency, using alternative energy, or a

combination of the two. As population of the world grows, so does the demand for clean

water and consequently, waste water treatment plants have not only become a major

consumer of energy, but also a major producer of greenhouse gases, mainly CO2.

Conventional waste water treatment plants using some variants of the activated sludge and

anaerobic digestion are typically running at an energy cost of 300 Wh/m3 or 1 MJ/m3, while

producing 0.26-0.8 kgCO2/m3. For a treatment plant with 350,000 m3/day capacity, these

numbers translate to 38,000 MWh/year and 33,215 tons of CO2 per year!


In this research programme, we proposed to develop a symbiotic hollow fiber membrane

photobioreactor (HFMP) that will reduce the demand of aeration energy in the activated

sludge waste water treatment plant and minimize the atmospheric venting of CO2. In this

HFMP, waste water containing activated sludge (represented by Pseudomonas putida) was

circulated through the lumen of the hollow fiber membranes while microalgae (Chlorella

vulgaris) were grown in the shell side of the bioreactor. The hollow fiber membranes

provided a barrier that separated the microalgae from the activated sludge while serving as

a gas exchange barrier to remove CO2 from the activated sludge side to the microalgae side,

and in reverse, transfer O2 produced by microalgae growth for waste water treatment,

thereby eliminating energy intensive aeration in the conventional activated sludge process.

In addition, future applications can see microalgal biomass harvested for other purposes, for

example, for food, biofuels and other high-value added products, like therapeutics.

Our results obtained from the developed HFMB demonstrated a proof-of-concept of the

symbiotic relationship that existed between microalgae growth and activated sludge waste

water treatment. In the absence of aeration in the waste water, glucose (at 1000mg/L) was

completely biodegraded in 12h, while microalgae grew continuously in the absence of

supplied CO2. The success of this concept prompted us with the innovative idea of perhaps

retrofitting all existing activated sludge treatment tanks, in the future, with a microalgae

culture by incorporating a flat sheet membrane between the two bioreactors for gas

exchange.


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“Using Protein Immobilized Membranes for Water Purification and

Treatment”

Yen Wah Tong Associate Professor Department of Chemical and Biomolecular Engineering, Division of Bioengineering National University of Singapore

Dr. TONG Yen Wah is an Associate Professor in the Department of Chemical and

Biomolecular Engineering, jointly appointed to the Division of Bioengineering, at the

National University of Singapore (NUS). He graduated with a PhD from the University of

Toronto in the field of biomaterials, with research on controlling nerve cell growth for spinal

cord regeneration. After joining NUS, his research has mainly been on using polymeric

materials for various biological and biomedical applications, including liver and neural tissue

engineering, through the synthesis of peptide-based biomaterials combined with a

polymeric microsphere scaffold. He has also worked on molecular imprinting of proteins for

protein separation and virus capture. His current interest is in growing microbes onto the

polymeric microsphere scaffold to be used in biotransformation - in the pharmaceutical

industry and in the wastewater treatment industry.


Aquaporins are water-channel membrane proteins that selectively allow the passage of

water molecules across the plasma membrane, while preventing ions and other solutes

from passing through. In this work, we have designed and fabricated a new aquaporin-

incorporated biomimetic membrane water purification and treatment. The approach for

constructing a biomimetic membrane is based on the use of a vesicular membrane, with

several parts, starting with the fabrication of aquaporin-incorporated lipid or polymer

vesicles, followed by vesicle immobilization on porous substrates, and finally elucidating the

bulk water permeability using a forward osmosis test unit and reverse osmosis test unit. The

resultant aquaporin-incorporated biomimetic membrane displays much higher water flux as

well as lower salt leakage than membrane without aquaporin.


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INVITED LECTURE:

“Scalable Processes to Pharmaceutical Intermediates and APIs

using Evolved Enzymes”

Steve Collier graduated from the University of Liverpool in 1994 with a B.Sc. (Hons) in

Chemistry with Industrial Chemistry. He stayed at Liverpool to pursue a PhD in heterocyclic

chemistry under the guidance of Dr. R. C. Storr, graduating in 1998. After a year of short

term contract work, he spent 2 ½ years at Ultrafine (now part of SAFC Pharma) progressing

to the position of Project Team Leader, working on complex custom synthesis and process

development projects. In 2001 he moved continents and joined the Chemical Development

Dept. of AMRI in Albany, NY, and worked on the development and optimization of a wide

range of chemical processes, for transfer to GMP kilo and pilot plant facilities. In 2005 he

moved to Singapore as a Team Leader to help establish and grow AMRI’s Singapore

Research Centre, working on projects including process development, custom synthesis,

library synthesis and medicinal chemistry.

In 2008, Steve joined Codexis Laboratories Singapore as Head of Chemical Development.

The role involved the design and development of robust processes to pharmaceutical

intermediates and APIs, leveraging Codexis’ enzyme evolution technology, working with

interdisciplinary teams of molecular biologists, analytical biochemists, process chemists, and

fermentation specialists. In early 2009 he became the head of Codexis’ Singapore operation,

as Director of R&D and General Manager of the site. In 2010, Steve was appointed as an

Adjunct Associate Professor at the Dept of Chemistry at Nanyang Technological University,

Singapore, and is also a member of the Editorial Advisory Board of the journal Organic

Process Research and Development.

Steve Collier

Director of R&D and General Manager

Codexis



Biocatalysis is becoming an increasingly important tool for the process chemist, and

biocatalytic reactions can be leveraged to provide products of exquisite stereopurity. The

development of directed evolution technologies has played a crucial role in enabling the

delivery of enzymes as green, efficient and robust catalysts at commercial scale. This

presentation will discuss the basic philosophy of directed evolution and its application to a

number of different targets and processes, using a diverse range of enzymes including

transaminases, acyltransferases, ketoreductases amongst others.


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*Divider labelled ‘Day 2’+


Day 2 – Thursday, 7 July 2011 (Morning)


Chairperson for morning session chair: Mr. George Lam Director of Operational Excellence (OE) & Sustainability GlaxoSmithKline

8:30-8:45 Coffee / Posters

8:45-9:00

WELCOME AND INTRODUCTION Mr. George Lam Director of Operational Excellence & Sustainability GlaxoSmithKline

9:00-9:45

KEYNOTE ADDRESS

“Process Intensification for Green Chemistry - Moving Flow Chemistry into Novel Process Windows”

Prof. Volker Hessel R&D Director, Institut für Mikrotechnik ; Mainz GmbH; Professor, Eindhoven University of Technology

9:45 - 10:15

GSM PROPOSAL UPDATE

“Crystallization in Emulsions”

Prof. Saif Khan Assistant Professor National University of Singapore

9:45 - 10:15

TEA BREAK


10:45-11:15

GSM PROPOSAL UPDATE “Formulation Approaches for Enhanced Drug Delivery using Mesoporous Silica and Carbon” Prof. Reginald Tan Associate Professor National University of Singapore

11:15-12:00

INVITED LECTURE “Emerging Membrane Technologies for Green and Sustainable Manufacturing of Pharmaceuticals and Fine Chemicals” Prof. Neal Chung Provost’s Chair Professor National University of Singapore

12:00-13:00

LUNCH

Day 2 – Thursday, 7 July 2011 (Afternoon) Green & Sustainable Manufacturing Symposium

Chairperson for afternoon session: Ms. Rachel Teo Senior Officer, Biomedical Science Singapore Economic Development Board

13:00-13:45

INVITED LECTURE

“Green Catalysis – The Science Behind Sustainable Manufacturing Processes” Prof. Andy Hor Professor, National University of Singapore Executive Director, Institute of Materials Science & Research, A*STAR


13:45-14:15

GSM PROPOSAL UPDATE “Exploring Modern Methods for Carbon- Carbon and Carbon-Heteroatom Bond Formation” Dr. Jayasree Seayad Scientist, Institute of Chemical and Engineering Sciences A*STAR, Singapore

14:15-14:45

TEA BREAK

14:45-15:15

GSM PROPOSAL UPDATE

“Organic Dye-Catalyzed Photoredox Chemistry Using Visible Light” Prof. Choon Hong Tan Associate Professor National University of Singapore

15:15-16:00

INVITED LECTURE

“Sustainability in Chemical Processes: Indicators and Systematic Methodologies” Prof. Konrad Hungerbuehler Professor, ETH Zurich

16:00-16:30

SYMPOSIUM CLOSING & PRIZE PRESENTATION “The GSK-Singapore Spotlight on Sustainability – Addressing Future Challenges Together” Mr. Kevin Lai Deputy Director, Biomedical Sciences Singapore Economic Development Board


INVITED LECTURE

“Process Intensification for Green Chemistry - moving Flow

Chemistry into Novel Process Windows”

Prof. Volker Hessel, born 1964, studied chemistry at Mainz University. He got his PhD in

the field of organic chemistry in 1993. The topic of his PhD thesis was structure-property

relationships of special supra-molecular structures, micelles and lyotropic liquid crystals,

constructed by so-called bi- or multi-polar amphiphiles with rigid core unit.

Since 1994 Prof. Hessel has been an employee of the Institut für Mikrotechnik Mainz

GmbH and since 1996 he became group leader for microreaction technology. In 1999 he

was appointed Head of the Microreaction Technology Department, formed at that time,

meanwhile named Chemical Process Technology. His fields of research comprise micro

process engineering for mixing, fine chemistry, fuel processing and heterogeneous

catalysis. In 2002 Prof. Dr. Hessel was appointed Vice Director R&D at IMM and in 2007 as

Director R&D at IMM.

Prof. Hessel has authored or co-authored about 190 peer-reviewed publications (with 26

extended reviews) and more than 180 conference papers with regard to chemical micro

process engineering, 15 book chapters, and 5 books.

In July 2005, Prof. Hessel was appointed as part-time professor at Eindhoven University of

Technology, TU/e. This professorship is under the umbrella of the Chemical Reactor

Engineering group of Prof. Dr.ir. Jaap Schouten in the Department of Chemical

Engineering and Chemistry. Prof. Hessel was appointed as honorary professor at the

Technical Chemistry Department at Technical University of Darmstadt in 2009. In 2011,

Prof. Hessel was appointed as full professor with a chair of “Micro Flow Chemistry &

Process Technology” at Eindhoven University of Technology.

Prof. Hessel received the AIChE award “Excellence in Process Development Research” in

2007. His Hirsch number (scientific impact measure) is 28. He received in 2010 an ERC

Advanced Grant about “Novel Process Windows” to build a group at TU/e on this subject.

A.o. Prof. Dr. Hessel was AIChE chair (US) “Microprocess Engineering”(2005-2008);

elected board member of the German industrial platform IP VT; member of the editorial

Volker Hessel

R&D Director

Institut für Mikrotechnik Mainz GmbH

Professor

Eindhoven University of Technology


boards of “Catalysis Today”, “Chemical Engineering Journal”, “Chemical Engineering

Technology”, “Recent Patents on Chemical Engineering”, and “Current Organic

Chemistry”; Topical chair at AIChE Spring conferences 2006+2007 and organising

committee member of symposia held at CHISA-6, ECCE-6 (EPIC), EUChemS and WCCE-8 as

well as chair of the program committees of the “Conference on Smart Synthesis and

Technologies for Organic Processes” (SynTOP) and the “International Conference on

Microreaction Technology 10” (IMRET-10).

Presentation Abstract

Micro Process Technology engineers and speeds up heat and mass transfer – transport

intensification. Novel Process Windows (NPW) offers in addition a chemical intensification

field to redesign chemical transformations and to massively speed up reaction kinetics [1, 2].

This often demands operation very different and far from the classical process sheets -

shifted to harsher conditions for process intensification (high-T, high-p, high-conc/solvent-

free, explosive or thermal runaway regime). The NPW approach also comprises, thirdly, a

process intensification field to make processes as a whole more cost-efficient and

sustainable. Process integration in time and space (all-at-once, direct route, one flow-multi-

step, transform to catalytic) opens ways to new/better products.

The interplay of different NPW routes will be demonstrated at the optimization of the

Kolbe-Schmitt reaction, expanding the performance obtainable through superheated

capillary processing as standard route and speeding up reactivity already by three-orders-of

magnitude (2000x). From there, a selectivity study of another flow process under

superheated conditions is done using a molecule with two same functionalities. Here, a

follow-up reaction can decrease the selectivity of the mono-substituted target product. A

capillary reactor based process converts dichloropropyl pivaloate, prepared from glycerol,

into 3-chloro-2-hydroxy-propyl ester and shows two orders-of-magnitude reduced reaction

times (240x); but also demon-strates limitations in NPW operation due to the chemical

multi-functionality. Some other instructive chemistry will make tangible the benefit of

exploring unusual chemical parameter space. Process integration will be demonstrated at

the example of gold nanoparticles making and other functional materials, decoupling and

NPW-optimizing formerly simultaneous steps. Plant integration will be shown at the

compact container plant Evotrainer of Evonik-Degussa which is a modular least-cost

investment unit of modular nature and amenable both to laboratory and production

development. First theoretical studies on process integration/simplification will be done in

the coming research through the ERC Advanced Grant “Novel Process Windows – Boosted

Micro Process Technology” - for the direct oxidation of cyclohexene (direct route), Click

Chemistry (multi-step one-flow), and hydroformylation (supercritical route).


Such step- and paradigm changing routes need at a very early stage guidance and evaluation through cost- and life-cycle (environmental) analysis, as the theoretical performance potential is often not even vaguely accessible and developments bear high technological risk. Such ex-ante evaluation was applied to current processes for glucose oxidation and possible improvements using microreactor technology – comparing noble metal catalyst versus enzymatic oxidation and conventional process conditions versus Novel Process Windows. The large impact of proper catalyst choice (wall coating, fixed bed, nano slurry) for the competitiveness of Flow Chemistry is then exemplified further at the copper-catalysed Ullmann ether synthesis, revealed through a full-process cost analysis, including catalyst preparation and product separation.

References [1] V. Hessel, Chem. Eng. Technol. 32 (2009) 1655–1681. [2] V. Hessel, B. Cortese, M.H.J.M. de Croon, Chem. Eng. Sci. 66 (2011) 1426.


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GSM PROPOSAL UPDATE

“Crystallization in emulsions”

Saif Khan

Assistant Professor

National University of Singapore

Saif A. Khan was born in Mumbai, India. He received his Ph.D. in chemical engineering from

the Massachusetts Institute of Technology in 2006, where he was an R. T. Haslam

Presidential Fellow.

In 2006 he joined the National University of Singapore (NUS) as Assistant Professor in

chemical and biomolecular engineering. He was appointed Fellow of the Singapore-MIT

Alliance (SMA) in Chemical and Pharmaceutical engineering in 2007.

His research interests include microfluidics, soft condensed matter physics, colloid science,

plasmonic nanomaterials and reaction engineering of non-equilibrium chemistries. His

research group at NUS focuses on various aspects of microscale fluid physics and

phenomena, with the aim of developing new experimental methods for chemistry and

biology that complement or extend existing macroscopic methods.


Crystallization plays an important role in the pharmaceutical industry for separation,

purification and formulation of active pharmaceutical ingredients (API). Crystal size, shape

and polymorphic form are important factors governing a wide range of crystal properties as

well as the physiological uptake of the drug.

Among existing methods to produce polymorph-specific crystals, emulsion-based

crystallization is an attractive process platform to simultaneously control both nucleation of

a specific API morphology, while producing crystal agglomerates of desired size and

spherical shape that greatly accelerate product formulation and eliminate costly

downstream processing.

In this talk, we will discuss the status and challenges in emulsion-based crystallization

processes. We will also summarize our recent research efforts in developing experimental

and modelling tools to help us unravel the physics of emulsion-based crystallization at a

hierarchy of length and time scales.


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GSM PROPOSAL UPDATE

“Formulation approaches for enhanced drug delivery using

mesoporous silica and carbon”

Reginald Tan

Associate professor


Prof Reginald Tan currently holds a joint appointment as Principal Scientist and Programme

Manager of Crystallisation and Particle Science at the Institute of Chemical & Engineering

Sciences (ICES), A*Star. He obtained his degrees in chemical engineering at Imperial

College, London, and the University of Cambridge, UK. Before joining NUS in 1990, he was a

Technology Projects Engineer at ICI Engineering in the UK. His research interests include

multiphase transport phenomena, crystallisation science and process development, particle

technology applications for pharmaceuticals, and environmental life cycle assessment.


Mesoporous materials possess large pore volumes and surface areas, making them suitable

as drug hosting/delivery systems with high drug loading and versatility in various

applications. In our research group, mesoporous silica and carbon have been used in the

formulation of poorly water-soluble active pharmaceutical ingredients (APIs) to improve

dissolution properties of oral dosage forms as well as to build up an effective diffusion

network for burst release of antibiotics from bone cement.

Depending on the pore size, the solid-state of the API can tailored to be amorphous or

nanocrystalline as the drug molecules are entrapped in the uniform nano-sized pore

channels by co-spray drying. The dissolution rate of co-spray dried API with mesoporous

silica or carbon was significantly enhanced as compared with the original untreated API. The

effect of particle size of mesoporous silica on dissolution rate of co-spray dried API was also

investigated. Moreover, the uniformly arranged mesoporous structure prevents the re-

crystallization or crystal growth during storage even under stressed test condition of

40°C/75%RH for over 1 year. Case studies demonstrated that mesoporous silica/carbon

provided an efficient drug hosting/delivery system for poorly water-soluble drugs, such as,

ibuprofen, indomethacin, fenofibrate and itraconazole.

In another application, commercial antibiotic-loaded PMMA-based bone cement showed

very low and limited (~5%) drug delivery efficiency with more than 90% of the antibiotic

entrapped in the bone cement matrix. To overcome this limitation, mesoporous silica


nanoparticles (MSN) were selected as the host for antibiotics and formulated with the bone

cement. Due to the hollow structured mesoporous channels within MSN nanoparticles, an

effective diffusion network was built up, which was responsible for the effective drug

diffusion from bone cement matrix to the external surfaces. MSN-formulated bone cement

was able to increase the drug release efficiency by 14-fold and sustain the release for up to

80 days. Superior to other fillers, MSN had no detrimental effect on the critical weight-

bearing bending modulus and compression strength of bone cement. In-vitro assay test

results showed a much sustained antibacterial effect and low cytotoxicity of MSN, hence

demonstrating the potential applicability of MSN-formulated bone cement.


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INVITED LECTURE:

“Emerging membrane technologies for green and sustainable

manufacturing of pharmaceuticals and fine chemicals”

Prof. Chung received his PhD from SUNY in Buffalo (USA) in 1981. He had worked for

Hoechst Celanese for 13 years and Aeroquip for 2 years in USA prior to joining NUS in 1995.

His research strengths are in polymeric membranes for water, energy, and life sciences. He

has received grants of about US$38 millions in the last 16 years. He has published more than

1 book, 16 book chapters, 50 patents, 382 journal papers and 300 conference papers. Prof

Chung is an Editorial Board Member of many journals including (1) J. Membrane Science, (2)

Desalination, (3) Separation and Purification Reviews, (4) Separation Science and

Technology, (5) Chemical Engineering J., (6) Chemical Engineering and Technology, (7)

Polymer Engineering and Science, J. (8) Applied Polymer Science, (9) Chinese J. Chemical

Engineering, (10) many others. His H-index is 40.

Prof. Chung was part of the team which invented, developed and commercialized Vectra™

liquid crystalline polymers with an annual business size of US$150 million in 1980s. From

2005-2008, he worked as a Senior Consultant for Hyflux (Singapore), led and built its

membrane research team. He was a co-inventor of Hyflux Kristal 600 ultrafiltration hollow

fiber membranes which commercialized worldwide. He received two IChemE (Institute of

Chemical Engineers) “Highly Recommended” Awards in Energy and Water, United Kingdom

in 2009, and IES (The Institution of Engineers, Singapore) Prestigious Engineering

Achievement Award, Hyflux‐SNIC (Singapore National Institute of Chemistry) Award in

Environmental Chemistry, and IChemE in Singapore Awards in Sustainability in 2010. He was

appointed as the Provost’s Chair at NUS in 2011.

Neal Chung

Provost’s Chair Professor




Clean water, renewable energy, and affordable healthcare are three major concerns globally

due to water scarcity, resource depletion, and high medical cost. Among many potential

solutions, advance in membrane technology is one of the most direct, effective and feasible

approaches to solve these sophisticated issues for chemical industries. Membrane

technology is a fully integrated science and engineering which consists of materials science

and engineering, chemistry and chemical engineering, separation and purification

phenomena, statistical mechanics-based molecular simulation, process and product design.

In this presentation, we will cover the following areas, but focus on green and sustainable

manufacturing of pharmaceuticals and fine chemicals:

1. Membrane R & D and technologies at NUS.

2. Challenges and design strategies to produce membranes for pharmaceuticals and

fine chemicals industries.

3. Molecular engineering of membrane materials and fabrication to recycle solvents

and water in pharmaceutical and chemical syntheses.


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INVITED LECTURE:

“Green catalysis – The science behind sustainable manufacturing

processes”

Andy Hor [D.Sc. (Lond), D.Phil. (Oxford), B.Sc.(Hon)(Imperial College), Postdoc(Yale)] is

Professor of Chemistry in the National University of Singapore and President of Singapore

National Institute of Chemistry. He has published over 240 international papers in

heterometallic syntheses, homogeneous catalysis and supramolecular assembly with about

3,500 citations and an h-index of 29. He has been conferred different fellowship such as

Humboldt, Wilsmour, Anthony Mason, Frances Lion Memorial, Jackson Memorial and

professorship at Nagoya, Sydney, Melbourne, Münster, Strasbourg, etc. He is the Associate

Editor (Commissioning) of Aust. J. Chem. (CSIRO) and member of the international advisory

panel of Chem. Asian J. (VCH/Wiley) and Inorg. Chim. Acta. (Elsevier)

He has delivered numerous invited/keynote/plenary lectures in different conferences and

symposia, and will chair the 41st International Coordination Chemistry Conference (ICCC) in

Singapore in 2014. To date, he has supervised about 30 Ph.D., 20 M.Sc. students and over

100 B.Sc. Hon students as well as 70 SRP, 15 SMP and over 80 school students on projects.

Over the years, he has received numerous teaching awards, including the Outstanding

Educator Award (NUS) in 2002. He is currently the advisor of Victoria Junior College,

Nanyang Girls’ High School and World Scientific.

Andy Hor

Professor, National University of Singapore

Executive Director, Institute of Materials Science &

Research, A*STAR



Behind a typical pharmaceutical manufacturing process is chemistry. However, even though

there is no such thing as “bad chemistry”, some manufacturing processes are just “bad”, in

the sense that they produce more than what the environment, or our globe, can swallow.

Chemistry has evolved to a stage when we examine not only the product of a reaction, but

its by-products. A magic product can make “big bucks” for the company, but some

unpleasant by-products, if not handled properly, can shake public confidence and break a

company. Many chemical reactions produce wonderful compounds, but they are not

suitable basis for a modern pharmaceutical process. There are many reasons, typical ones

including poor yield and selectivity.

But, increasingly, other factors are being scrutinised such as reaction medium, number and

nature of by-products, temperature and pressure, entropy and enthalpy considerations,

mass conservation etc. If there is a singular solution to these challenges, it is probably

catalysis. Catalysis is the key to a green and sustainable process. In this presentation, the

speaker will focus on something fundamentally important – design of catalyst and what it

can do. Examples are drawn from the findings in his laboratory. (Ref 1)

Ref 1: F. W. Li and T. S. A. Hor, Chem. Eur. J., 2009, 15, 10585; S. Q. Bai, L. L. Koh and T. S. A. Hor,

Inorg. Chem., 2009, 48, 1207; Z. Wang, C. W. Kee, S. Li, T. S. A. Hor and J. Zhao, Appl. Cat. A Gen.,

2011, 393, 269.


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GSM PROPOSAL UPDATE

“Exploring Modern Methods for Carbon- Carbon and Carbon-

Heteroatom Bond Formation”

Jayasree Seayad

Scientist

Institute of Chemical and Engineering Sciences, A*STAR, Singapore

Dr. Jayasree Seayad completed her Ph.D in chemistry in the field of homogeneous catalysis

at the National Chemical Laboratory, India in 2000. Following this she carried out two years

of postdoctoral research at the Leibniz Institute of Catalysis (LIKAT), Rostock, Germany. In

2004-2005 she was awarded the prestigious Alexander von Humboldt (AvH) research

fellowship to carry out postdoctoral research at the Max-Planck-Institut fur

Kohlenforschung, Muelheim an der Ruhr.

Jayasree joined A*STAR in 2006: 2006-2009-Institute of Bioengineering and

Nanotechnology; 2009- present, Institute of Chemical and Engineering Sciences. Her

research focus is on sustainable methods for organic synthesis by organo- and transition

metal catalysis, C-H functionalization, C1 chemistry and synthesis of biologically active small

molecules.


Catalytic C-C and C-heteroatom bond forming reactions are extremely important in organic

synthesis. Researchers in both academia and industry are continually looking for new

sustainable methods to construct these bonds with special attention on atom economic

scalable processes using readily available feedstock and environmentally benign

reagents/catalysts. In this talk our recent endeavours on the development of various C-C, C-

N and C-O bond forming reactions using organo- and transition metal catalysis will be

discussed.

In the first part of the talk, N-heterocyclic carbene (NHC)-catalyzed C-N and C-C bond

forming reactions for the synthesis of N-phenylisoxazolidin-5-ones, -amino acid esters, N-

phenylhydroxamic acids and N-tosyloxazolidinones will be presented. Subsequently, a Cu

catalyzed C-O bond formation by the dioxygenation of olefins to form vicinal diacetates and

tetrahydrofuran derivatives will be discussed. Finally, some of our current activities on the

C-C bond forming reactions of arenes by C-H activation supported by GSK-EDB-GSM fund

will also be highlighted.


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GSM PROPOSAL UPDATE

“Organic Dye-Catalyzed Photoredox Chemistry Using Visible Light”

Tan Choon Hong

Associate professor


Choon Hong received his PhD from the University of Cambridge in 1999. Following that, he

carried out postdoctoral training at the Department of Chemistry and Chemical Biology,

Harvard University. Subsequently, he worked as a Research Associate at Department of

Biological Chemistry and Molecular Pharmacology, Harvard Medical School. He joined the

Department of Chemistry, NUS in 2003 and was promoted to Associate Professor in 2010.

Choon Hong has successfully developed a new class of catalysts based on a biomimic

approach of a single amino acid, arginine. He demonstrated that these catalysts can be

useful for a large range of reactions that can be useful to prepare pharmaceutically active

and enantiomerically pure compounds.

He gained international recognition by winning the Asian Core Lectureship Awards from two

countries: Hong Kong and Japan. He won the UK Singapore Partners-In-Science

Collaboration Development Awards in 2008, the Young Chemist Award and the Young

Scientist Award in 2009 and the GSK-SNIC Organic Chemistry Award 2011.


Nature’s ability to convert solar energy to chemical energy has been an inspiration to

generations of chemists. During the course of mimicking nature’s elegant process, many

photoredox catalysts have been developed and they have been found applications in solar

energy storage, water splitting, air purification and photovoltaics. Recently, they are also

found to catalyze several organic transformations successfully. We have developed several

reactions using organic dyes as catalysts. In this seminar, we will discuss these

developments in our laboratory.


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INVITED LECTURE

Sustainability in Chemical Processes: Indicators and Systematic

Methodologies

Prof. Hungerbühler is the leader of the Safety and Environmental Technology Group

at ETHZ. His research topics cover the environmental and safety oriented assessment

of chemical products and processes.

Prof. Hungerbühler received his Diploma in Chem. Engineering in 1976 and his Dr. Sc. Tech. in 1979 from ETH Zurich. After receiving his doctorate in 1976, he worked as a Project Engineer in the Central Process Engineering Group at Ciba-Geigy, Basel. In 1983, he was promoted to the Head of Process Development at Ciba-Geigy, Grenzach. In 1989, he became the Head of Research and Development of Textile Dye Stuffs at Ciba-Geigy, Basel. He joined ETH Zurich in 1994 and has been the Professor of the Safety & Environmental Technology Group since then.


The fact that sustainability metrics should be considered in combination with traditional

economic objectives in the design and operation of chemical plants is nowadays common

knowledge, although not yet fully common practice. A reason for this is the complicated

multi-objective nature of the problem, since various and possibly competing aspects of

sustainability exist, including for instance minimization of process hazards and risk in plant

operation along with optimal use of resources. Another reason is that the quantification of

these principles through accurate, yet easy-to-calculate sustainability metrics still poses a

great challenge. Especially in early stages of process design, where considering sustainability

objectives can be quite advantageous since changes are easier to implement, data are

usually scarce and do not allow detailed LCIA or typical hazard identification and risk

analysis studies (e.g. HAZOP, FMEA, etc.) stipulating data available only at later design

stages.

Konrad Hungerbuehler

Professor

ETH Zurich


To tackle this problem, there have been many efforts to introduce and compare

sustainability metrics in the form of indices for screening diverse design options. This lecture

first presents an exemplary indicator framework for hazard identification that can be used

for both substance and process assessment in early design phases. Then, it is demonstrated

how traditional cradle-to-gate energy related impacts of chemical production can be

approximated with available databases and short-cut tools. The lecture includes motivating

examples from the field of waste solvent management, waste mixing optimization, and

process flow sheet analysis that illustrate the advantages of multi-criteria assessment at

different stages of conceptual process design. It is intended to highlight both state-of-the art

advantages and current challenges in applying indicator-based multi-criteria assessment in

chemical process design.


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SYMPOSIUM CLOSING & PRIZE PRESENTATION

“The GSK-Singapore Spotlight on Sustainability – Addressing Future

Challenges Together”

Kevin Lai joined the Singapore Economic Development Board (EDB) in 1999. During his time

in EDB, Kevin spent 4 years in New York as Centre Director before returning to Singapore to

head up the Medical Technology industry group. He was again posted to London in 2009 as

the Regional Director for Europe. He took on the latest appointment in 1st July 2011.

Kevin graduated from the University of Sheffield, UK with a Bachelors in Chemical

Engineering (Hons). He is married with a son.

Presentation abstract:

The GSK-Singapore Partnership – Addressing Future Challenges together

The challenge to make cost-effective medicines for the world is aligned will require a leap in

the way we think about designing a medicine and manufacture it. GSK and Singapore

believe that, through a collective investment in the GSK-Singapore Green & Sustainable

Manufacturing Partnership, Singapore will be poised to deliver the transformational impact

in next-generation pharmaceutical manufacturing processes in Asia, enhancing companies’

productivities and ability to deliver medicines to the world.

Kevin Lai

Deputy Director, Biomedical Sciences

Singapore Economic Development Board


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