Chair
Professor Chi-Ming Che, University of Hong Kong, P R China
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Professor Chi-Ming Che, University of Hong Kong, P R China
Professor Chi-Ming Che, University of Hong Kong, P R China
Professor Chi-Ming Che received his BSc and PhD in 1978 and 1982, respectively, from The University of Hong Kong (HKU). From 1980 to 1983, he studied at the California Institute of Technology under the guidance of Professor Harry B Gray. Thereafter, he returned to his alma mater, where he was promoted to Chair Professor of Chemistry in 1992. Since 1997 he has been the Dr Hui Wai-Haan Chair of Chemistry in HKU. His research interests include inorganic and organic synthesis; metal-ion promoted organic transformations; reactive metal-ligand multiple bonded complexes; inorganic photochemistry; luminescent materials; bioinorganic chemistry; and inorganic medicines. Over 100 PhD students have successfully completed their studies at HKU under his supervision. With more than 700 publications and an H-index of 78, Professor Che is one of the ISI Highly Cited Researchers. He is a current member of the international advisory board of Chemistry-A European Journal, Chemistry-An Asian Journal, Chemical Science, ChemCatChem, ChemPlusChem and Journal of Inorganic Biochemistry.
In 1995 Professor Che was elected as a member of the Chinese Academy of Sciences and became the first CAS member from Hong Kong and the youngest CAS member at that time. He was elected as a Fellow of World Innovation Foundation (2004), a Fellow of Federation of Asian Chemical Societies (2005), a Fellow of TWAS in Chemical Sciences (2007), and a Fellow of The Royal Society of Chemistry (2009). He received the following awards or prizes: National Natural Science Prize of China (1993), Croucher Senior Fellowship (1997), Chung-Hsing S&T Lectureship (1997), Distinguished Research Achievement Award of the University of Hong Kong (2000), IUF Invited Professorship of France (2000), Federation of Asian Chemical Societies Foundation Lectureship (2003), Visiting Scientist of National Research Council of Italy (2004), Pfizer Signature Lecture (2006), TWAS Prize in Chemistry (2006), 1st Class State Natural Science Award of China (2006), Seaborg Lectureship at the University of California at Berkeley (2007), Prize of Ho Leung Ho Lee (HLHL) Foundation for Scientific and Technological Progress (2007), Edward Clark Lee Lectureship at University of Chicago (2008), the Leader of Year 2008 Hong Kong (Research), Fellow of Royal Society of Chemistry (2008) and Molecular Sciences Forum Lecture Professorship at Institute of Chemistry, CAS (2009).
Interactions of intercalating photooxidising dipyridophenazine metal complexes with DNA
Professor John Kelly, Trinity College Dublin, Republic of Ireland
Abstract
For many years dipyrido[3,2-a:2’,3’-c]phenazine (dppz) complexes have been extensively studied as probes for DNA.
[Ru(phen)2(dppz)]3+ (phen = 1,10-phenanthroline) has attracted particular attention as it acts as a DNA-light switch, being non-luminescent in water but emitting when bound to DNA. By contrast [Ru(TAP)2(dppz)]2+ (TAP = 1,4,5,8-tetraazaphenanthrene) [2] and [Cr(phen)2(dppz)]3+ [3] are luminescent in aqueous solution but not upon binding to DNA. This is due to reduction of the metal complex excited state by guanine as has been demonstrated by picosecond transient spectroscopy (with both visible and IR monitoring) for [Ru(TAP)2(dppz)]2+ [2] and also for [Re(CO)3(dppzF2)]2+ [4].
Although it is accepted that the dppz ligand intercalates between the DNA base-pair, the precise mode of binding deduced from spectroscopic and biophysical measurements has been a matter of debate. Recent successful crystallisation by the Cardin group of both Ru(TAP)2(dppz)]2+ [5] and [Ru(phen)2(dppz)]2+ [6] with small defined-sequence DNA has for the first time provided a wealth of information on the interaction of these complexes with DNA and allowed a comparison with other DNA- intercalating molecules
References
[1] B M Zeglis et al, Chem Comm, 2007, 44, 4565-4579
[2] B Elias et al, Chemistry – Eur J, 2008, 14, 369-375.
[3] M Wojdyla et al, Photochem. Photobiol. Sci, 2010, 9, 1196-1202.
[4] Q Cao et al, Photochem. Photobiol. Sci, 2011, 10, 1355-1364.
[5] J P Hall et al, Proc Natl Acad Sci, 2011, 108, 17610-17614
[6] H Niyazi et al, Nature Chemistry, 2012, in press.
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Professor John Kelly, Trinity College Dublin, Republic of Ireland
Professor John Kelly, Trinity College Dublin, Republic of Ireland
John Kelly obtained his BSc from the University of Manchester, MSc from McMaster University (supervisor, John McCullough) and PhD from the University of London (supervisor, George Porter). After a Leverhulme Teaching Fellowship at the University of the West Indies, Jamaica and postdoctoral work at the Max Planck Institut für Strahlenchemie, Mülheim he joined Trinity College Dublin as a lecturer in 1973. He was elected as Fellow in 1978, promoted to Associate Professor in 1987 and to Professor of Chemistry in 2006. He was Director of Science of Materials (1989-1973), Head of the Department of Chemistry (1994–2000) and the first Director of the Dublin Chemistry Graduate Programme (2008-2010). He is currently Fellow Emeritus. His research interests are in photochemistry, transient spectroscopy, nucleic acids, photo-active metal complexes and nanoparticles, with applications in bio-sensing and energy conversion.
Metal photocleavage of DNA
Dr Samantha Higgins, Virginia Tech, USA
Abstract
Ru(II) and Os(II) polypyridyl chromophores have been readily studied for applications in DNA photomodification due to their enhanced photophysical and interesting photochemical properties. Coupling a Ru(II) or Os(II) chromophore to a remote bioactive site, such as Pt(II) or Rh(III), through a polyazine bridging ligand provides a supramolecular complex characterized by redox, spectroscopic, and photophysical properties. Studies of the mixed-metal complexes in the presence of DNA show enhanced photoinduced activity using low energy visible light within the therapeutic window (600-900 nm). The supramolecular complexes, [(Ph2phen)2MII(dpp)PtIICl2]Cl2 (Ph2phen = 4,7-diphenyl-1,10-phenanthroline and M = Ru(II) or Os(II)) display unique DNA photobinding and photocleavage properties by utilizing their lowest lying 3metal-to-ligand charge transfer (3MLCT) excited state to facilitate ligand loss at the remote Pt(II) center. Modifying the molecular architecture to [(TL)2MII(dpp)RhIIICl2(TL’)](PF6)3 (TL = terminal ligand on the chromophore, M = Ru(II) or Os(II) and TL’ = terminal ligand on the Rh(III) center) provides for distinctive oxygen independent photobinding and photocleavage features, a result attributed to unit population of the 3MLCT excited state, which is coupled to the lower lying 3metal-to-metal charge transfer (3MMCT) excited state. The varied mechanisms of DNA photocleavage in these supramolecular systems provide a fresh look at mixed-metal systems in photodynamic therapy.
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Dr Samantha Higgins, Virginia Tech, USA
Dr Samantha Higgins, Virginia Tech, USA
"Dr Samantha L H Higgins graduated from Randolph-Macon College, Ashland, VA in 2006 with her BSc in chemistry. Recently, Samantha received her PhD from Virginia Polytechnic Institute & State University, Blacksburg, VA. She studied mixed-metal supramolecular complexes and their applications in photodynamic therapy, under the direction of Professor Karen J Brewer."
Multifunctional in cellulo probes
Dr James Thomas, University of Sheffield, UK
Abstract
Ruthenium(II) polypyridyl complexes that interact reversibly with DNA can display high binding affinities and selectivities [1,2] as well as interesting photophysical properties [3]. Although such complexes offer potential as in cellulo probes for luminescence microscopy, poor cellular uptake by live cells restricts the use of such molecules.
In recent studies we have shown that complexes such as 1 and 2 are taken up by both live eukaryotic and prokaryotic cells where they bind to nuclear DNA as evident by both luminescence and transmission electron microscopy[4] suggesting they may find use as cellular specific imaging agents and/or therapeutics [5].
A distinctive property of 2 - revealed by in vitro and in cellulo studies - is that high affinity binding of specific DNA structures leads to distinctive emission signatures [4,6].Herein we present progress in this area, including structural studies aimed at delineating the cause of this complex’s structural binding preferences [7].
Acknowledgments: We thank EPSRC for its Life science DTC and PoC fund.
References
[1] (a) C Metcalfe, J A Thomas, Chem Soc Rev2003, 32, 214. (b) M R Gill, J A Thomas, Chem Soc Rev, in press.
[2] P Waywell, V Gonzalez, M R Gill, H A Adams, A J H M Meijer, M P Williamson, J A Thomas, Chem Eur J, 2010, 16, 2407.
[3] (a) S P Foxon, M Towrie, A W Parker, M Webb, J A Thomas, Angew Chem Int Ed,2007, 46, 3686-3689. (b) V G Gonzalez, T Wilson, I Kurihara, A Imai, J A Thomas, J Otsuki, Chem Commun 2008, 168.
[4] M R Gill, J Garcia-Lara, S J Foster, C G W Smythe, G Battaglia, J A Thomas, Nat Chem, 2009, 1,662-667.
[5] M R Gill, H Derat, C G W Smythe, G Battaglia, J A Thomas, ChemBioChem, 2011, 12, 877.
[6] T Wilson, M P Williamson, J A Thomas, Org Biomol Chem, 2010, 8, 2717.
[7] T Wilson, P J Costa, V Felix, M P Williamson, J A Thomas, in preparation.
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Dr James Thomas, University of Sheffield, UK
Dr James Thomas, University of Sheffield, UK
Jim Thomas was educated at the Universities of Reading and Birmingham. Following postdoctoral work with Jean-Marie Lehn in Strasbourg and Chris Hunter in Sheffield, he stayed in Sheffield to take up a Royal Society University Research Fellowship, becoming a permanent member of staff in 2004. He is currently a Reader in Coordination Chemistry. His research involves molecular recognition of anions, molecules and biomolecules, self-assembly, and the construction of functional molecular architectures.
Targeted photodynamic therapy
Professor David Phillips CBE, Imperial College London, UK
Abstract
Photodynamic therapy, PDT, is a minimally invasive procedure used in treating a range of cancerous diseases, infections, and in ophthalmology to treat the wet form of age-related macular degeneration. The photodynamic action relies upon the simultaneous interaction between a sensitiser molecule [non-toxic in the absence of light], visible light, and molecular oxygen. The sensitiser, usually a porphryin –related molecule, excited initially to the singlet state, intersystem crosses to a longer-lived triplet state, which then produces reactive oxygen species , ROS, primarily singlet oxygen resulting from electronic energy transfer.
Current photodynamic therapy (PDT) of cancer is limited by inefficiencies involved in specifically targeting photosensitisers to tumours. Although antibodies are being explored as targeting vehicles, they present significant challenges, particularly in terms of pharmacokinetics and drug-coupling. We describe here a novel and effective system to attach covalently multiple photosensitiser molecules (both pre-clinical, pyropheophorbide-a and clinically approved, verteporfin photosensitisers) to single-chain Fvs. Further, we demonstrate that not only do the resulting photoimmunoconjugates retain photophysical functionality, they are more potent than either free photosensitiser, effectively killing tumour cells in vitro and in vivo. For example, treatment of human breast cancer xenografts with a photo-immunoconjugate comprising an anti Her-2 scFv linked to 8 molecules of pyropheophorbide-a leads to complete tumour regression. These results give an insight into the important features that make scFvs good carriers for PDT drugs, and provide proof of concept of this unique approach to targeted photodynamic therapy (tPDT). This promises to significantly improve upon current photodynamic therapy for the treatment of cancer and paves the way for clinical application.
A second means of introducing selectivity in PDT is through spatial selection , using two-photon excitation of the sensitiser. This has the advantage of using red or near infra-red light, which greatly enhances tissue penetration. We describe the synthesis of porphyrin dimers with very large two-photon cross sections,carried out by Professor Harry Anderson’s group in Oxford, and their effect in vitro on two cell types, and in sealing blood vessels in vivo.
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Professor David Phillips CBE, Imperial College London, UK
Professor David Phillips CBE, Imperial College London, UK
David Phillips is a graduate of the University of Birmingham, [BSc Chemistry 1961, PhD 1964, Honorary DSc, 2011]. He carried out post-doctoral work in the University of Texas at Austin, 1964-6, [Fulbright Scholar], and the Institute of Chemical Physics, Academy of Sciences of USSR, Moscow 1966/7, before beginning his University teaching and research career at the University of Southampton, Department of Chemistry, in 1967. He then moved to London in 1980 as Wolfson Professor of Natural Philosophy at the Royal Institution, and in 1989 became Hofmann Professor of Chemistry at Imperial College London, 1989-2006, Head of Department 1992-2002. He served as Dean for the Faculties of Life Sciences and Physical Sciences, 2002-2005, and Senior Dean, 2005/6 at Imperial. He is author of some 590 articles and reviews in his field of photochemistry, and received the Porter Medal of the European, Oceanic, and Inter-American Photochemistry Associations 2010 for this work. He is a committed populariser of science; and was awarded the Michael Faraday Award of the Royal Society in 1997 was awarded an OBE in 1999 for services to science education, and CBE in the 2011/12 New Year’s honours list for services to Chemistry. He is currently President of the Royal Society of Chemistry.