Faculty Name
Hiroyuki HIRAOKA Professor
Doctoral and Postdoctoral Training Ph.D., Kyoto University (1959).
Junior Research Chemist, University of California, Los Angeles (1960-62).
Research Chemist, University of California, Berkeley (1962-63).
Selected Previous Positions
Research Areas
Research Staff, IBM Photochemistry of simple molecules and Research Division (1966! polymeric materials; surface chemistry;
90). polymers and advanced materials.
Visiting Professor, University of Bordeaux (1990).
YUNai-Teng
Ligand binding to metalloporphyrins and hemoproteins; organometallic chemical bonding; laser-based spectroscopy and applications; cataract/vision research;
biomedical instrumentation.
Total synthesis of clinical and pharmaceutical agents; naturally occurring drugs from Chinese plants; nuclear medicine.
Biosensors and bioelectronics;
bioanalytical chemistry; environmental chemistry; medical diagnostics; protein engineering.
Chemical composition of medicinal plants;
development of natural therapeutics;
analytical techniques for natural products;
literature database.
Biophysical and bioinorganic and bioanalytical chemistry; materials science.
Theoretical organic, bioorganic and bioinorganic chemistry.
Asymmetric synthesis; synthetic methodology development; catalysis;
organometallic chemistry; CNS drug design.
Wei-MinDAI
Synthetic organic and bioorganic chemistry; asymmetric reactions and synthesis methodology; synthesis of natural products and biomedically interesting molecules; drug design, synthesis, and mechanism; synthesis of molecules for advanced mat\)rials; porphyrin analog synthesis.
Organometallic chemistry; materials synthesis; homogeneous catalysis; metal hydride chemistry.
Inorganic and organometallic synthesis;
homogeneous catalysis; materials syntht<sis; bioinorganic chemistry.
Theoretical inorganic chemistry; clusters and metal-silane complexes.
Polymer chemistry; materials science;
synthetic chemistry; organometallics;
liquid crystals; chiral polymers; optical materials; drug delivery.
Novel analytical techniques and trace analysis; drug analysis and metabolism;
cobalamin chemistry; environmental chemistry; isolation and characterization of fullerene compounds.
Materials and solid state chemistry; X-ray crystallography; nonlinear optical materials; electrical properties of organic compounds.
Optimal control chemistry by light;
molecular nonlinear spectroscopy in condensed phases; theory of chemical reaction and charge transfer; molecular dynamics and cooperativity; computational methods in chemical physics of complex systems.
ShiheYANG Assistant Professor
Lam Lung YEUNG Assistant Professor
Ph.D., Rice University (1988).
Postdoctoral Fellow, Argonne National Laboratory (1988-89).
Postdoctoral Fellow, University of Toronto (1989-92).
Ph.D., Imperial College of Science &
Technology (1992).
Postdoctoral Fellow, University of Cambridge (1993).
Gas phase clusters; nanomaterials;
fullerene derivative materials.
Organic synthesis and drug design;
asymmetric catalysis.
Research Projects
Boron-Mediated Catalytic Asymmetric Carbon-Carbon Bond Forming Reactions for the Synthesis of Enantiomerically Pure Pharmaceuticals
Paul R. CARLIER (PI), Wei-Min DAI RGC Project no. HKUST 203/93E ($472,000)
Recently announced US FDA guidelines have placed great emphasis on developing new drugs in enantiomerically pure form. In the past, the importance of administering pharmaceuticals in enantiomerically pure form was not widely appreciated, and until 15 years ago, there were few economical methods for the preparation of drugs in this form. Thus most drugs were developed in racemic form (a 1:1 mixture of "left-" and
"right-hand" forms). The goal of our research is to develop new and practical asymmetric methods for the preparation of pharmaceuticals. To do this we will develop and use chiral reagents to mediate known organic reactions. Current investigations include the use of chiral boron and lithium reagents in aldol and Diels-Alder reactions.
Solution Structure, Asymmetric Aldol, and Asymmetric Alkylation Reactions of Lithia ted Nitriles
Paul R. CARLIER ' ,
RGC Project no. HKUST 588/59P ($401,000)
Lithiated nitriles are useful intermediates in organic synthesis, but little is known regarding their structure in solution. We propose to develop asymmetric alkylation and aldol reactions of nitriles. In parallel with this study, we will use multinuclear NMR spectroscopy to unambiguously determine solution structures of a variety of lithiated nitriles in different solvents. The ultimate goal of these studies is to determine what correlation exists benyeen the solution structure and reactivity of these reagents.
Antibody-Catalyzed Epoxidation Reactions for the Synthesis of Anti-inflammatory and Antihypertensive Agents
Paul R. CARLIER (PM), Peter H.Y. LAM (BICH), Kwong-Kee WAN (BIOL)
UGC Project no. RI93/94.SCOI [$435,000 (Year 1)] Dr Wan left HKUST on I July 1994. Project completed This project aims at the creation of novel antibodies that catalyze both well-established and less-explored reactions that are important for the synthesis of pharmaceuticals. This multidisciplinary approach synergistically combines the strengths of synthetic chemistry, immunochemistry, and recombinant DNA technology. Current investigations focus on development of antibodies for the synthesis of intermediates leading to anti-inflammatory and anti-hypertensive drugs.
Tasks in Chinese Medicine and Other Natural Products Chun-Tao CHE
UGC Project no. CA92/95.SC01 [$512,000 (to HKUST)] Joint project with CUHK, HKU, and HKBU
This project has initiated an inter-institutional collaborative programme to facilitate scientific study of Chinese medicines and other natural products. The specific tasks of this programme can be grouped into three areas.
The first involves making information from the Chinese Medical Material Research Centre's database on scientific and clinical studies of Chinese medicine available for on-line searching by UPGC-funded institutions.
The second is aimed at enhancing herbal safety by monitoring and providing information and scientific support in cases of herbal poisoning as well as consolidating intemationa'l links with poison centres and toxicology laboratories world-wide. The third area involves basic training of students in biomedical and health-related disciplines on selected topics related to Chinese medicines. These activities are intended to promote research into Chinese medicine, improve the regulation of the herbal industry, and provide proper health care to patients using Chine~e medicine.
Chinese Herbal Drugs: Chemical Assessment and Quality Control Chun-tao CHE
RGC Project no. CPDG94/95.SC09 ($31,500) Project completed.
In order to ensure efficacy and safety of Chinese medicinal herbs, it is essential to establish guidelines and procedures for standardization and quality control. This research will establish criteria and standardized procedures for chemical characterization of selected herbal materials.
Antihormonal Substances and Inhibitors of 5-Reductase and Aromatase from Natural Source Chun-tao CHE
RGC Project no. HKUST 589/95P ($431,000)
Benign prostatic hyperplasia (BPH) [enlarged prostate] is a common neoplastic growth in men causing urinary flow obstruction at the bladder neck and other complications including prostate cancer. Current pharmacological knowledge on the pathogenesis of BPH strongly suggests that antihormonal compounds and Sa-reductase and/or aromatase inhibiting compounds can offer significant beneficial effects in BPH patients.
This project will initiate a search for antihormonal substances and enzyme inhibitors from Chinese herbs. The objectives include: (a) assessment of herbal preparations by enzyme assays and cell cultures for androgen and oestrogen deprivation activities, (b) purification and structural determination of the active principles, and (c) modification of chemical structures and evaluation of the analogues for activity. ' '
Experimental Studies of Intermolecular Interactions in Solution PeijunCONG
RGC Project no. DAG95/96.SC14 ($80,000)
Design and Synthesis of Potent DNA-Cleaving and Anticancer Agents by in situ Formation of tO-Membered Ring Enediyne Structures
Wei-MinDAI
RGC Project no. HKUST 212/93E ($462,000)
The goal of this project is to design and synthesize two types of novel enediyne pro-drugs which would be converted into 10-mempered ring enediyne structures by the designed activation process under physiological conditions. New synthetic schemes to prepare the target molecules of this study will be developed. Novel intermediate compounds made during the synthesis will be available to produce the related DNA-damaging agents other than the enediyne compounds. Biological activity of the synthesized agents will be tested.
Design and Synthesis of Analogs of Enediyne Anticancer Antibiotics An Investigation on the Mechanism of Action ofKedarcidin and C-1027 Chromosphores
Wei-MinDAI
RGC Project no. HKUST 590/95P ($670,000)
Kedarcidin and C-1027 chromophores are the new members of the naturally occurring enediyne family and their structures were disclosed in 1992-1993. These substances form diradical species by a cycloaromatization of the nine-membered ring enediyne core under the physiological conditions and damage DNA by abstraction of hydrogen atoms from the sugar residue of DNA leading to DNA strand cleavage. This project aims at understanding the mode of action of these substance by investigating the radical-forming reaction cascade in model compounds. Synthesis of the designed model compounds will be car~ied out in the laboratory. It is expected that the developed synthetic schemes and a better understanding of the mode of action will provide a foundation for further development of enediyne anticancer agents.
Alkaloid-Catalyzed Enantioselective Synthesis
Wei-Min DAI (PI), Xiao-Jiang HAO (Kunming Institute of Botany, Chinese Academy of Sciences, PRC), Hua-Jie ZHU (Kunming Institute of Botany, Chinese Academy of Sciences, PRC), Xiao-Sheng YANG (Kunming Institute of Botany, Chinese Academy of Sciences, PRC)
Kunming Institute of Botany (RMB¥20,000)
isolated from the seeds of plants collected in Yunnan Province, PRC and modified chemically to a suitable catalyst for enantioselective alkylation of diethylzinc with aldehydes. Other types of reactions may be examined as well.
Studies on Novel Enediyne Compounds Wei-MinDAI
Shirley Boyde Trust/HKUST ($15,000)
Enediyne antitumor antibiotics are a class of novel substances recently discovered in fermentation broths and exhibiting very promising biological activity. This project, together with other ongoing research activities of this group, will focus on the synthesis of structurally simplified enediyne molecules related to the naturally occurring antibiotics. New reactions and methods of synthesis will be developed.
The Development of Novel Asymmetric Homogeneous Catalysts Based on New Enantiomerically Pure Phosphine Ligands
Richard K. HAYNES
RGC Project no. DAG94/95.SC07 ($100,000) Project completed.
,
The most common phosphine ligands for asymmetric homogeneous catalysts are cis-chelating diphosphines, which contain non-chiral phosphorus with homo- or heterochiral substituents which impart overall chirality.
The preparation ofP-chiral phosphines encounters problems of configurational control at phosphorus, thus most effort focuses on preparation of P-chiral phosphines. However, the limiting factors in all preparations are high cost of chiral auxiliaries used for the preparation of homochiral reagents, and the non-trivial resolution of the chiral phosphine precursors used in the preparation of the P-chiral phosphines. Because our method involves use of nucleophilic phosphorus, we can prepare a wide range of targets. Further, we are not restricted to use of tert-butyl ,and phenyl as the incipient stereodifferentiating sl,Jbstituents on phosphorus. Other secondary phosphines bearing aryl and alkyl groups can be prepared also, and resolved via the phosphinothioic acids. We are using the method to prepare a wide range of enantiomerically pure tertiary phosphines. Coupled with this, we shall evaluate those structural features of catalysts, both experimentally, and by computation, which imprint high stereosectivity upon commercially-important catalysed reactions. Our method will then be used to prepare a number of structurally distinct ligand types whose efficiencies in these asymmetric catalysed processes will then be assessed. Promising compounds will then be carried forward for evaluation on large scale, dependent upon industrial collaboration.
Rational Evolution of Trioxane Antimalarials Agents as Generalised Chemotherapeutic Agents:
Investigation of Basic Chemistry of 1,2,4-trioxane and Related Systems, Method of Preparation and Chemical Basis for Therapeutic Mode of Action
Richard HAYNES
HKUST Rand D Corporation Project no. RDC95/96.SC01 ($267,364)
This industrially supported project involves the chemical modification of the famous peroxidic Chinese antimalarial qinghaosu or artemisinin such that it will be made suitable for targeting other sites of drug action rather than that in the malarial parasite. The key aims are to firstly make the substance more stable by removong the oxygen atom from C-1 0, and to replace this with groups linked by carbon such that intercalation or binding to DNA will be exclusively observed.
With its active tricixane pharmacophore, the modified artemisinin derivatives should then be capable of cleaving DNA based on its free-radical mode of action. In addition it is nepessary to attach glycoside and amino-acid residues such that binding to the minor groove will be effected. The preparation of the new derivatives will be accompanied by biological testing such that cytotoxicity may be used as a guide for possible drug effects.
Artemisini11 Analysis
Richard HAYNES (PM), Terence S.M. WAN
Roche Asian Research Foundation Project no. RARF94/95.SC01 ($43,025) Project completed.
This project involves the analysis of blood samples from patients in Vietnam having been administered with artemisinin and its derivatives, which are new antimalarial drugs. The methodology employed has recently been developed in the PI's laboratory, and involved capillary gas chromatography- mass spectrometry with selected
Novel Oxygen Transfer Reactions - Generalized Preparation and Chemistry of 1,2,4-Trioxanes with Reference to the Chinese Peroxidic Antimalarial Qinghaosu
Richard HAYNES
RGC Project no. HKUST 59l/95P ($630,000)
The advent of qinghaosu with its outstanding antimalarial activity has attracted world-wide attention, both from biological, and in our case, chemical perspectives. The current project addresses several inter-related issues.
We need to emulate the manner in which nature produces qinghaosu in Artemisia annua, for then we will be able to prepare totally synthetic analogues in the laboratory, and we will no longer be reliant on a plant source for this type of drug, of importance from an industrial viewpoint. We need to understand howqinghaosu exerts its antimalarial activity, so that we can rationally design more active analogues. The underlying problem in understanding the mode of action of this class of drug is that the chemical behaviour of 1,2,4-trioxanes is poorly understood, especially in the presence of metal ions. Additionally, an understanding of the way in which we can assemble the trioxane structure will provide insight into the manner in which it breaks down as the parent drug exerts its antimalarial activity. Thus the project objectives of preparing these compounds and examining their chemistry, both as a means of understanding biological activity and developing new drugs, but above all, of providing a fundamental contribution to chemical knowledge, are inextricably linked.
Rational Evolution of Trioxane Antimalarials Agents and Generalised Chemotherapeutic Agents:
Investigation of Basic Chemistry of 1,2,4-Trioxane and Related Systems, 'Methods, of Preparation and Chemical Basis for Therapeutic Mode of Action
Richard HAYNES (PI), Wei-Min DAI, Wa Hung LEUNG, Zhenyang LIN, Terence S.M. WAN, Yun-Dong WU, Lam-Lung YEUNG
UGC Project no. RI94/95.SC03 ($1,159,000)
The advent of qinghaosu with its outstanding antimalarial activity has attracted world-wide attention. However, the basis of the project is to design new drugs with optimal activities, not only for treatment of malaria, but also for other pathogenic organisms, and even tumour cells. The key issue here is that the trioxane nucleus of qinghaosu is capable of producing 'active' oxygen species under carefully controlled conditions, and as such may be capable of hydroxylating DNA bases. This project entails an in-depth examination of QHS and analogues, with the broad perspectives of acquiring knowledge on the chemistry and biological behaviour of trioxane systems, and of developing new drugs not only for treatment of malaria, but also other diseases. The chemical and spectroscopic properties of the trioxanes, particularly in the presence of metal ions, will be delineated. Acquisition of an understanding of the nature of the biosynthetic process, the chemistry, and mode of action will then enable us to optimize the design and synthesis of candidate drugs which incorporate the 1,2,4-trioxane nucleus. Biological studies will examine the interaction of artemisinin with biological targets such as DNA, measurement of drug activities in vitro and in vivo, and development of an analytical method suitable for evaluation of pharmacological profiles of the drug candidates.
Asia Photochemistry Conference Hiroyuki HIRAOKA
Croucher Foundation Project no. CF95/96.SC19 ($100,000)
Sub-100 mm Size Domain Chemistry for Molecular Assembly Hiroyuke HIRAOKA
RGC Project no. HKUST 587/95P ($421,000)
Pulsed Laser Chemistry for Deposition, Etching and Surface Modification 1 Hiroyuki HIRAOKA
RGC Project no. HKUST 627/94P ($791,000)
Pulsed uv-laser irradiation of materials such as polymers and semiconductors generates effects different from those generated by continuous-wave (CW) photo-irradiation. Short-pulse uv-light exposures cause very rapid heating and cooling, which in turn can cause the photoablation of polymers and/or annealing of semiconductor surfaces. Using this technique we have deposited crystalline diamonds on silicon for the first time. Another new application of this pulsed laser irradiation involves the use of polarized light emitted by the Nd:YAG laser.
vertical walls over a wide area. We have also succeeded in laser-induced conversions of hydrophobic to hydrophilic and ofhydrophilic to oleophilic natures with Nd:YAG laser.
Training of Miwon Staff and Development of 1-Line Photoresist Technology Hiroyuki HIRAOKA
Miwon Commercial Company Project no. MCC95/96.SC01 ($100,000)
Study of Deep UV Light Processes Hiroyuki HIRAOKA
NEC Corporation Project no. NEC92.001 ($97,200)
This is a donation from NEC to my research activities in the field of deep UV -processes, which include micro-pattern fabrication/ generation, laser deposition using deep UV light, deep UV photoresist processing including reactive ion etching.
Deep UV-Light Processes Hiroyuki HIRAOKA
NEC Corp. (¥500,000 per year)
Deep UV-light (200-300 nm) applications to sub-1/2-micron device fabrication are investigated. We are successful in sub-1/4-micron Si pattern fabrication using the Nd:Y AG laser. We are also investigating deep UV-photoresist systems.
Laser-Assisted Chemical Vapor Deposition of Advanced Opto-Electronic Materials (Joint departmental project)
Hiroyuki HIRAOKA (PM,), Shihe YANG, Rong-Fu XIAO (PHYS), Man WONG (ELEC) UGC Project no. Rl92/93.SC06 ($1,067,000) Project completed.
Crystalline diamond films are successfully deposited onto heated silicon surfaces by excimer laser ablation of polymers in a reactive atmosphere. The study for further improvement of the process is in progress. In particular, ':"e would like to lower the substrate temperature required for ablation (now at 650' C) and extend the technique to other surfaces (e.g., silicon carbide). In addition, other important materials like silicon carbide, silicon nitride and carbon nano-tubes will be studied for laser-induced deposition from the vapor phase.
The Design and Synthesis of Novel Chiral Chelating Phosphine Ligands and the Application of them in Asymmetric Catalysis
Guochen JIA
Croucher Foundation Project no. CF94/95.SC07 ($548,000)
Chiral compounds are important for food, pharmaceutical and agrochemical industries because optical isomers often show distinctly different physiological properties when applied to biological systems. The most attractive route to synthesizing optically active compounds is to use transition metal complex-catalyzed asymmetric synthesis because large amounts of optically pure compounds can be made with very small amounts of chiral catalysts. Crucial to the development of practical asymmetric catalysis is the design and synthesis of chiral ligands. Hence,. the objectives of the proposed research are: (1) to design and synthesize chiral chelating polydentate, especially tridentate phosphine, ligands for homogeneous catalysis; (2) to prepare catalytically active transition metal complexes of these novel ligands; and (3)
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study the chemical and catalytic properties of the new metal complexes. Besides the possibility of yielding valuable catalysts for practical applications, completion of the proposed research will also increase knowledge of asymmetric catalysis with chelating phosphine ligands. Consequently these results will help us to understand the requirements for generating effective catalysts and to design better ligands for practical applications.Development of Advanced Materials Derived from Novel Conjugated Polymers Guocheng JIA (PI), Wa-Hung LEUNG
RGC Project no. HKUST 202/93E ($482,000)
Conjugated polymers have emerged in the last decade as one of the most exciting topics in physical science because of their unusual properties and potential technological applications. This research aims at the synthesis, characterization, and identification of the applications of novel conjugated polymers with backbone-containing heteroatoms, in particular phosphorus, arsenic, silicon, germanium, and transition metals. Incorporation of heteroatoms such as phosphorus and metals into polymers would result in a vast diversity of novel molecular structures, electronic perturbation and therefore novel properties. One class of our target conjugated polymers
Conjugated polymers have emerged in the last decade as one of the most exciting topics in physical science because of their unusual properties and potential technological applications. This research aims at the synthesis, characterization, and identification of the applications of novel conjugated polymers with backbone-containing heteroatoms, in particular phosphorus, arsenic, silicon, germanium, and transition metals. Incorporation of heteroatoms such as phosphorus and metals into polymers would result in a vast diversity of novel molecular structures, electronic perturbation and therefore novel properties. One class of our target conjugated polymers