Dr Stephen Faulkner

Reader in Chemistry

Email: stephen.faulkner@manchester.ac.uk

Tel: +44 (0)161 2754659

Fax: +44 (0)161 275498

Brief Biography
I took my first and second degrees at the University of Oxford, before moving to the University of Durham to take up an Addison Wheeler fellowship in 1993, where I worked in collaboration with David Parker and Andy Beeby. I then took up a lectureship at the University of Surrey in September 1998 and moved to the University of Manchester in May 2001.

Research Interests

My interests lie in designing and making systems with interesting photophysical properties, which can be used to probe supramolecular interactions. My main interests centre on the synthesis and use of lanthanide complexes as imaging and contrast agents, as conjugates with bioactive peptides and as probes of protein structure. I am also interested in the design of carceplexes containing phosphorescent chromophores and in the application of low molecular weight targeting vectors to chemotherapy. Research is currently funded by EPSRC, MRC and the Wellcome and Leverhulme Trusts, as well as a variety of industrial concerns.

Research within the group covers a variety of areas, and entails a mixture of synthesis and spectroscopy. Our goal is to develop new systems for imaging and diagnosis, and for use in targeted therapy.

Synthesis

Azamacrocycle chemistry

The azamacrocycle cyclen is an ideal scaffold for two to four pendent arms, and can be used to build molecules that form very stable complexes with lanthanide ions. These are used in a wide variety of applications, but particularly in medical imaging using MRI and luminescence. Many of the molecules we make contain this unit and incorporate unusual chromophores or targeting vectors.

People involved: Rebecca Aarons, Ben Burton-Pye, Ben Dadds, Simon Pope, Emma Shiells, Steve Wray, Maite Jauregui, Aaron Villaraza, Thelma Koullourou, Louise Natrajan

Peptide conjugates with lanthanide complexes

We have been linking lanthanide complexes in conjunction with small bioactive peptides to form ��smart�� imaging agents. As well as using conventional peptide coupling methods, we are also investigating the use of more unusual reactions, such as the Ugi reaction, to form conjugates.

People involved: Rebecca Aarons, Emma Shiells, Jianghua Feng, Marco Meloni, Maite Jauregui

Solid and surface supported lanthanide complexes

We have prepared a range of solid supported ligands which can bind to lanthanide ions, and used these to assist in purification of conjugates and complexes, and have also prepared a range of thiol appended ligands that can be self-assembled onto surfaces

People involved: Rebecca Aarons, Ben Burton-Pye, Marco Meloni

Polynuclear lanthanide complexes

Polynuclear lanthanide complexes have potential advantages over mononuclear complexes as imaging agents as a result of their increased bulk and the simple increase in the number of metal ions. We have prepared a range of these using simple building blocks to form polynuclear complexes, and have recently developed methods to make stable heteronuclear complexes, like that shown above, selectively.

People involved: Ben Burton-Pye, Ben Dadds, Simon Pope, Steve Wray, Emma Shiells, Aaron Villaraza, Thelma Koullourou, Ben Moss

Incarceration of organic chromophores

Outside the area of lanthanide chemistry, we are working on the preparation of carcerands which incorporate aromatic chromophores. Incarcerated molecules are known to have unusual photophysical properties, and can be stabilized in otherwise hostile environments.

People involved: Bimbisar Desai, Dan Sykes

Spectroscopy

Lanthanide and Actinide Luminescence

One of our main interests is in the luminescence from lanthanide (and actinide) ions using time resolved laser spectroscopy. This is much longer lived than fluorescence from organic molecules, and can be used in time-gated imaging applications. In recent years, we have demonstrated near IR luminescence from lanthanides such as neodymium, ytterbium, praseodymium and erbium, and shown how iterative reconvolution techniques can be used to obtain luminescence lifetimes. We have also probed the mechanism of energy transfer in lanthanide complexes containing aromatic chromophores, and are investigating the luminescence properties of other lanthanides and actinides, as well as that of transition metal complexes

People involved (past and present):

Rebecca Aarons, Ben Burton-Pye, Ben Dadds, Simon Pope, Emma Shiells, Steve Wray, Louise Natrajan, Thelma Koullourou, Amanda Bailey, Marie-Christine Carrie, Adam Dubas

Luminescent d-block complexes

Metal to Ligand Charge Transfer (MLCT) states result in luminescence from a range of transition metal complexes we are particularly interested in luminescence from polypyridyl complexes with rhenium, technetium, ruthenium, osmium and platinum, and in developing methods to study stable analogues of complexes used in radioimaging techniques such as PET and SPECT.

People involved: Simon Pope, Nathalie Thao-Thion, Thelma Koullourou

Luminescence and energy transfer processes in polynuclear complexes

Complexes containing more than one lanthanide ion can have unusual spectroscopic properties. We have shown how the excited states of transition metal complexes can be used to transfer energy to luminescent lanthanide ions. Very recently, we have also shown that energy transfer from one lanthanide to another can result in lanthanide centred lanthanide luminescence. We have begun to study the possibility of energy up-conversion in solution in polynuclear complexes where the metal-metal distance is comparable to that in solid oxides. Energy up-conversion occurs in the solid state when two photons of low energy are absorbed and one is emitted at higher energy.

People involved: Ben Burton-Pye, Simon Pope, Emma Shiells, Thelma Koullourou

Imaging

Imaging and parallel processing

The light emitting properties of lanthanide ions can be combined with microscopy techniques in biological imaging applications. Since lanthanide luminescence is long lived, background fluorescence can be rejected. This can be combined with lifetime mapping (essentially measuring the lifetime of each pixel in the image) to allow more than one lanthanide to be used at once. These can be used to measure a number of variables in sensor applications, or alternatively can be used to encode information

People involved: Rebecca Aarons, Ben Burton-Pye, Marco Meloni, Jianghua Feng

Molecular devices

Self- assembled arrays of complexing agents can also be used to prepare luminescent sensors, either as sensors or in luminescent arrays for microlithography. We are currently investigating the selective formation of such arrays, which may have applications in high-resolution displays.

People involved: Ben Burton-Pye, Louise Natrajan

Therapy

Smart peptide conjugates

Low molecular weight targeting vectors such as peptides can be used to deliver a complexed metal ion to a diseased cell. We are interested in using such vectors to image and destroy damaged cells. Lanthanide complexes can be used with a range of imaging techniques, and are readily synthesised and purified. Our main target is the development of complexes incorporating peptide sequences that act as integrin receptor antagonists, and can be used to image and inhibit the spread of tumours. We are currently also investigating the use of targeting vectors which allow us to image the immune response to a wide range of tissue damage. This approach also allows us to attempt imaging of ischaemic stroke, and may assist in the developments of treatments for patients suffering inflammation in the aftermath of stroke.

People involved: Rebecca Aarons, Emma Shiells, Marco Meloni

Recent publications

Edited works (contributions).

1. S. Faulkner and J.L. Matthews, Fluorescent and Luminescent complexes for Biomedical Applications, Chapter in Volume 9 of Comprehensive Coordination Chemistry 2^nd Edition, Applications of Coordination Chemistry (ed. M.D. Ward), Elsevier 2004

2. S. Faulkner and R.J. Aarons Imaging and Targeting, an invited review for the Encyclopedia of Supramolecular Chemistry, Dekker, 2004

3. Synthesis of Thiopyranones, S. Faulkner, R.C. Whitehead and R.J. Aarons, Science of Synthesis. Chapter 7, Volume 14, Thieme, 2003.

4. Parallel processing in aqueous solution; S. Faulkner, D. Parker & J.A.G. Williams, Chapter 4 in NATO Advanced Study series 'Supramolecular science: where it is and where it is going', ed. R. Ungaro, Kluwer (1999).

Refereed primary contributions

5. Lithium selective ionophores based on pendant arm substituted crown ethers: S. Faulkner, R. Kataky, D. Parker & A.Teasdale, J. Chem.Soc. Perkin Trans 2 (1995), 1761-1769.

6. An efficient metal templated route to C-functionalised derivative of 12aneN4; C.D. Edlin, S. Faulkner, D. Parker & M.P. Wilkinson Chem. Commun (1996), 1249-1250.

7. Luminescence from neodymium ions in solution, A. Beeby & S. Faulkner. Chem. Phys. Lett. (1997), 266, 116-122.

8. Luminescence from ytterbium and its complexes in solution; A. Beeby, R.S. Dickins, S. Faulkner, D. Parker & J.A.G. Williams Chem. Commun. (1997), 1401-1402.

9. Structural investigations of benzyl phosphinate bearing complexes of lanthanides; S. Aime, A. Batsanov, A. Beeby, M. Botta, R.S. Dickins, S. Faulkner, C.E. Foster, J.A.K. Howard, T.J. Norman, D. Parker & J.A.G. Williams, J. Chem. Soc. Dalton Trans. (1997), 3623-3636.

10. Luminescence of Lanthanide ions in reverse micelles; A. Beeby, I.M. Clarkson, J. Eastoe, S. Faulkner & B. Warne, Langmuir. (1997), 13, 5816-5819.

11. Relaxometric luminescence behaviour of a triaquohexaazamacrocyclic complex displaying a high relaxivity with pronounced pH dependence; J. Hall, R. Hamer, S.Aime, M.Botta, S.Faulkner, D.Parker & A.S. DeSousa, New J. Chem. (1998), 627-631.

12. Ligands derived from C-aryl substituted derivatives of cyclen: formation of kinetically unstable complexes with lanthanide(III) ions; C. D. Edlin, S. Faulkner, D. Parker, M. P.Wilkinson, M. Woods, J. Lin, E. Lasri, O. Neth & M. Port, New J. Chem. (1998), 1359-1364.

13. Generating a warm glow: luminescence in the near-IR by neodymium and ytterbium complexes; S. Faulkner, A. Beeby, D. Parker & J.A.G. Williams, J. Fluoresc. (1999), 45-49.

14. The effect of X-H oscillators on luminescence quenching in lanthanide complexes; A. Beeby, I.M. Clarkson, R.S. Dickins, S. Faulkner, D. Parker, A.S. de Sousa & J.A.G. Williams, J. Chem. Soc. Perkin Trans 2, (1999), 493-503.

15. Time resolved imaging microscopy using stable lanthanide chelates; A.Beeby, I.Clarkson, S. Faulkner, S. Botchway, D. Parker & A.W. Parker, J. Photochem. Photobiol. B Biol, (2000), 57, 83-89.

16. Synthesis and luminescence properties of europium complexes excited at 410nm: evidence for the intermediacy of the aryl triplet state, S.Faulkner, A. Dadabhoy & P.G. Sammes. J. Chem.Soc. Perkin Trans. 2, (2000), 2359-2360.

17. Time-resolved near-IR luminescence from ytterbium and neodymium complexes of the Lehn cryptand. S. Faulkner, A.Beeby A, M.C. Carrie, A. Dadabhoy, A.M. Kenwright, P.G. Sammes, Inorg. Chem. Commun., 2001, 4, 187-190.

18. Sensitised luminescence from phenanthridine appended lanthanide complexes: analysis of triplet mediated energy transfer processes in terbium, europium and neodymium complexes, A. Beeby, S. Faulkner, D. Parker, J.A.G. Williams , J. Chem. Soc. Perkin Trans. 2, 2001, 1268-1273

19. Energy transfer processes in antenna appended lanthanide complexes and arrays, S. Faulkner, J. Inorg. Biochem., 2001, 86, 46.

20. Long wavelength sensitizers for europium(III) luminescence based on acridone derivatives, A. Dadabhoy, S. Faulkner, P.G. Sammes , J. Chem. Soc. Perkin Trans. 2, 2002, 348-357.

21. Synthesis and near-IR luminescence properties of neodymium(III) and ytterbium(III) complexes with poly(pyrazolyl) borate ligands, A. Beeby, B.P. Burton-Pye, S. Faulkner, G.R. Motson, J.C.Jeffery, J.A. McCleverty, M.D. Ward, J. Chem. Soc. Dalton Trans., 2002, 1923-1928.

22. pH Dependence of the energy transfer mechanism in a phenanthridine-appended ytterbium complex, A. Beeby, S. Faulkner, J.A.G. Williams, J. Chem. Soc. Dalton Trans., 2002, 1918-1922.

23. Parallel addressing of luminescent lanthanides., S. Faulkner, B.P. Burton-Pye, A. Beeby, S. FitzGerald, M.D. Ward, P.S. Goodall, Abst. Pap. Am. Chem. Soc., 2002, 223, 123-nucl.

24. Interaction between tetrathiafulvalene carboxylic acid and ytterbium D03A: solution state self-assembly of a ternary complex which is luminescent in the near IR, S. Faulkner, B.P. Burton-Pye, T. Khan, L.R. Martin, S.D.Wray, P.J. Skabara, Chem. Commun. 2002, 1668-1669.

25. Lanthanide derived imaging agents, R.J. Aarons, B.P. Burton-Pye, S. Faulkner, S.W. Botchway, A.W. Parker, S. Topley, A. Beeby, J.S. Snaith, A. Ashraf, J. Notta, LSF Ann. Rep., 2001/2002, 130-133.

26. Visible-light sensitisation of near-infrared luminescence from Yb(III), Nd(III) and Er(III) complexes of 3,6-bis(2-pyridyl)tetrazine, N.M. Shavaleev, S.J. A. Pope, Z.R. Bell, S. Faulkner, M.D. Ward, Dalton Trans., 2003, 808-814.

27. Near-IR luminescence sensitized by luminescent platinum complexes, N.M. Shavaleev, L.P. Moorcraft, S.J. A. Pope, Z.R. Bell, S. Faulkner, M.D. Ward, Chem. Commun., 2003, 1134-1135.

28. Luminescent complexes from arrays of lanthanide ions, S.J.A. Pope and S. Faulkner, Abst. Pap Am. Chem Soc. 2003, 922-ino.

29. A binuclear ytterbium complex with differentiated binding sites, S.J.A. Pope, S.L. Heath, A.M. Kenwright and S. Faulkner, Chem. Commun. 2003, 1550-1551.

30. N.M. Shavaleev, L.P. Moorcraft, S.J. A. Pope, Z.R. Bell, S. Faulkner, M.D. Ward, Chem. Eur. J.., 2003, 9, 5283-5291.

31. Lanthanide Sensitized Lanthanide Luminescence; S.J.A. Pope and S. Faulkner, J. Am. Chem. Soc. 2003, 125, 10526-10527.

32. Synthesis and Luminescence Properties of dinuclear lanthanide complexes derived from covalently linked macrocyclic ligands, S.J.A. Pope, V. Boote, A.M. Kenwright and S. Faulkner, Dalton Trans, 2003, 3780-3784.

33. Structural and near-infrared photophysical studies on ternary lanthanide complexes containing poly(pyrazolyl)borate and 1,3-diketonate ligands, G.M. Davies, R.J. Aarons, G.R. Motson, J.C. Jeffery, H. Adams, S. Faulkner and M.D. Ward, Dalton Trans. 2004, 1136-1144.

34. Pyrene-sensitised Near-IR luminescence from ytterbium and neodymium complexes, S. Faulkner, M-C. Carri̩, S.J.A. Pope, J. Squire, A. Beeby and P.G. Sammes, Dalton Trans, 2004, 1405-1410.

35. Photoinduced Ru-Yb energy transfer and sensitised near-infraredluminescence in a coordination polymer containing co-crystallised [Ru(bipy)(CN)4]2- and Yb(III) units, T.A. Miller, J.C. Jeffery, M.D. Ward, H. Adams, S.J.A. Pope and S. Faulkner, Dalton Trans, 2004, 1524-1526.

36. Re(I) sensitised near-infrared lanthanide luminescence from a hetero-trinuclear Re₂Ln array, S.J.A. Pope, B.J. Coe and S. Faulkner, Chem. Commun., (2004), 1550-1551.

37. S.J.A. Pope, B.J. Coe, S. Faulkner, E.V. Bichenkova, X. Yu, K.T. Douglas, J. Am. Chem. Soc., 2004, 126, 9490-9491

38. Synthesis and luminescence properties of nitro and aminobenzyl functionalised DO3A derivatives, R.J. Aarons, S.J.A. Pope and S. Faulkner, Dalton Trans. in press

39. Preparation of heterobinuclear lanthanide complexes by programmed self-assembly, B.P. Burton-Pye and S. Faulkner, Chem. Commun, 2005,259.

40. Incorporation of a hydralazine derived chromophore into a series of kinetically stable lanthanide complexes, B.P. Burton-Pye, S.L. Heath and S. Faulkner, Dalton Trans. 2005, 146-149

41. Metal-to-ligand charge-transfer sensitisation of near-infrared emitting lanthanides in trimetallic arrays M2Ln (M = Ru, Re or Os; Ln = Nd, Er or Yb), S.J.A. Pope, B.J. Coe and S. Faulkner, Dalton Trans 2005, 1482-1490.

42. Lanthanide(III) Complexes of a Novel Schiff-base Bibracchial Lariat Ether: Structural characterization and Photophysical Properties, M. Gonz��lez-Lorenzo, C. Platas-Iglesias, F. Avecilla, S. Faulkner, S.J.A. Pope, A. de Blas and T. Rodr��guez-Blas, Inorg Chem., 2005, 44, 4254-4262

43. Structural and Photophysical Properties of Coordination Networks Combining [Ru(bipy)(CN)4]2- Anions and Lanthanide(III) Cations: Rates of Photoinduced Ru-to-lanthanide Energy Transfer and Sensitized Near-infrared Luminescence, G.M. Davies, S.J.A. Pope, Harry Adams, S. Faulkner, and M.D. Ward, Inorg Chem., 2005, 44,

44. DNA Mismatch Detection by Resonance Energy Transfer Between Ruthenium(II) and Osmium(II) Tris(2,2?-bipyridyl) Chromophores, E.V. Bichenkova, X. Yu, P. Bhadra, H. Heissigerova, S.J.A. Pope, B.J. Coe, S. Faulkner, K.T. Douglas, Inorg Chem. 2005, 44, 4112-4114.

45. Sensitised Near Infrared Emission from Lanthanides via Anion-Templated Assembly of Heteronuclear [2]Pseudorotaxanes M.R. Sambrook, D. Curiel, E.J. Hayes, P.D. Beer, S.J.A. Pope and S. Faulkner, submitted to J. Am. Chem. Soc.

46. A smart luminescent probe containing a tuftsin targeting vector coupled to a terbium complex, R.J. Aarons, J. Notta, M.M. Meloni, J. Feng, S. Allan, N. Spencer, R.A. Kauppinen, J.S. Snaith and S. Faulkner submitted to Chem. Commun.

47. Synthesis and luminescence properties of nitro and aminobenzyl functionalised DO3A derivatives, R.J. Aarons, S.J.A. Pope and S. Faulkner, Dalton Trans. submitted

Review Articles:

48. Lanthanide Probes for Optical Imaging Applications, S. Faulkner, B.P. Burton-Pye and S.J.A. Pope, invited review for Applied Spectroscopy Reviews, (2005), 40, 1.

49. Targeting Vectors for Imaging Agents and Radiopharmaceuticals. S. Faulkner and J.S. Snaith, Eur. Pharm. Rev. 2004 (2), 33