Professor Sofia I. Pascu FRSC FHEA

Professor in Bioinorganic and Materials Chemistry, University of Bath

Academic Visitor, Oxford Siemens Molecular Imaging Laboratory, Inorganic Chemistry Laboratory, University of Oxford

email: s.pascu@bath.ac.uk and sofia.pascu@chem.ox.ac.uk

Bath University Research group website: since October 2007

Main research interests: Metals in medicine, homegeneous- and nano-catalysis and synthetic functional materials

• Multimodal PET/optical molecular imaging techniques: Targeted delivery of metallodrugs, encapsulated within Single Wall Carbon Nanotubes, Dynamic Nanohybrids and Nanocapsules
• Designing new radiopharmaceuticals for PET or SPECT imaging and/or therapy; radiolabelling methods with Cu-64, Ga-68 and Zr-89
• Multiphoton fluorescence imaging techniques: confocal fluorescence and lifetime fluorescence imaging (FLIM) of metallic species in cancer cells
• Pseudorotaxane-type structures for molecular switches
• Synthetic coordination and organometallic chemistry with sustainable chemistry applications
• Homogeneous catalysis using tripodal N-heterocyclic carbenes, i.e. Pd(II) and Cu(I), for C-C coupling reactions such as Sonogashira, Suzuki and Heck reactions
• Functional materials for Fischer Tropsch chemistry and Sustainable Chemistry Applications
• Single crystal X-ray diffraction using synchrotron radiation
• Designing light emitting hybrid nanomaterials and donor-acceptor supramolecular complexes for photovoltaic applications
• Covalent and non-covalent functionalisation of graphene, graphene oxide, carbon nanoparticles and single walled carbon nanotubes

Targeted delivery of metal ions encapsulated within single wall carbon nanotubes and dynamic nanocapsules

Several drug delivery and targeting strategies have been developed that are based on coupling drugs to receptor-specific ligands and/or protection of the drug by wrapping it in a polymer or lipid coat. We insert metallic ions such as Cu radioisotopes into more kinetically stable transport systems and then guide these to the target by conjugation to an appropriate targeting biomolecule.

‘Hot’’ complexes or ionic materials will be encapsulated inside carriers, i.e. single wall carbon nanotubes SWNTs (a), or nanocapsules (b). These assemblies are derivatised with groups able to modulate the lipophilicity (e.g. carboxylate units, also suitable for further synthetic modifications), to provide biological targeting (i.e. an address, which is an antibody or related biological molecule incorporating recognition motifs, linked covalently or non-covalently to the main ‘carrier’) or to provide a fluorescent tag (e.g. dansyl chloride, nitrobenzaoxadiazoles for monitoring the delivery process and cell uptake studies).

a) SWNTS as carriers for ‘hot’ metal ions – collaboration with Oxford Nanotube Group and Oxford Siemens Molecular Imaging Laboratory

b) Formation of nanocapsules as hosts for ‘hot’ metal ions – collaboration with Dr Sijbren Otto (Cambridge)

Designing new Cu-64 radiopharmaceuticals for PET imaging and therapy

Positron emission tomography (PET) will be one of the primary tools for the diagnosis of cancer and for the monitoring of the effects of therapy. Therefore, there is a great interest in developing new target-specific radiopharmaceuticals. This synthetic programme identifies target complexes to be synthesised, cell delivery and targeting strategies, and methods for testing these in biological systems. Copper-64 is both a beta and positron emitter, offering the possibility of simultaneous imaging and therapy. The relatively long half-life of ⁶⁴Cu (12.7 hours) makes it an attractive isotope for PET imaging since it can carried out on a site remote from the cyclotron used to generate the radionuclide. Despite this there are very few available bifunctional copper chelators (based on nitrogen, phosphorus and oxygen donors) with optimal physical characteristics in terms of neutral charge, redox and kinetic stability. While based on known coordination chemistry principles, the successful synthesis of ‘hot’ complexes will represent a significant step forward in the use of Cu-based imaging agents. This work is currently carried out in collaboration with Professor Jon Dilworth and his research group within CRL. Radiolabelling studies are carried out in collaboration with the Centre for Molecular Imaging of Functional Biological Systems, Oxford as well as Addenbrooke’s Hopsital (Wolfson Brain Imaging Centre, led by Dr Frank Aigbirhio). Feedback from the testing is incorporated into optimising the complex design.

Supramolecular homogeneous catalysis

The development of homogeneous catalysts that rival the efficiency and selectivity of enzymes is one of the holy grails in chemistry. My objective is to use dynamic combinatorial chemistry (DCC) to discover highly selective homogeneous metallic catalysts. This overcomes problems of prior synthetic approaches, in which the “trial and error” synthesis of selective catalysts is rarely successful and immensely time-consuming. The DCC strategy to generate specific receptors has already been making an impact in academia, but this research has not yet been extended to homogeneous transition metal catalysis of processes of industrial relevance. This work is sponsored by a Royal Society Joint Collaboration Grant, with Professor Makoto Fujita

Pseudorotaxane-type structures for molecular switches

One of the key goals of supramolecular chemistry is to assemble structural building blocks into arrays with new properties that emerge only in supramolecular architectures. Rotaxanes and catenanes have for some time been the subject of intense study both because of their fascinating architectures and because they may have useful properties as molecular level switches and sensors. We are interested in applying this fundamental knowledge to develop molecular assemblies that can perform tasks analogous to the machines of everyday life.

My approach has been to bring together neutral electron-rich components and electron-poor components to create donor–acceptor systems that are neutral, chemically robust and capable of post-synthetic modification. These weak non-covalent interactions can be reinforced under the effect of alkali salts. This work is in collaboration with Prof Jeremy Sanders (Cambridge).

Synthetic coordination and organometallic chemistry

My general objectives are to understand the intimate mechanisms of important catalytic reactions and to discover and study new catalytic processes. My recent work has been concerned with late TM catalysts for C-C coupling reactions, and with establishing new Fe(II)-based organometallic systems active in homogeneous Fischer-Tropsch (FT) catalysis.

Single crystal X-ray diffraction using synchrotron radiation

A vital component of my work is to characterise the complexes synthesised and their precursors crystallographically. Redox-related changes in biological properties of copper-bis(thiosemicarbazone) radiopharmaceuticals such as hypoxia tracer diacteylbis(4-methyl-3-thiosemicarbazonato)copper(II) Cu(ATSM) are mediated by changes in core structural parameters. A good understanding of single crystal X-ray structures provides considerable insight into solid state packing interactions, which play a significant part in determining fluorescence lifetimes and efficiencies of the compounds of interest.

Many of the single crystal structures are amenable to solution using the laboratory-based equipment in Bath, but a large number of inorganic and organometallic precursors afford only small weakly diffracting single crystals. Additional X-ray flux available on Station 9.8 was necessary to provide good quality data. As a trained SRS user, I carried out the experimental work at Daresbury and all structural analysis. Collaborative support was provided by Prof Paul Raithby (Bath) and Dr John Warren (SRS Daresbury/Bath).

Selected Publications

1. S. I. Pascu*, N. Kuganathan , L. H. Tong , R. M. J. Jacobs, P. J. Barnard , B. T. Chu , Y. Huh, G. Tobias , C. G. Salzmann , J. K. M. Sanders, M. L.H. Green, J. C. Green, Interactions between Tripodal Porphyrin Hosts and Single Walled Carbon Nanotubes: an Experimental and Theoretical (DFT) Account J. Mater. Chem., 2008,18, 2781.
2. S. I. Pascu*, P. A. Waghorn, T. D. Conry, B. Lin, H. M. Betts, J. R. Dilworth, R. B. Sim, G. C. Churchill, F. I. Aigbirhio, J. E. Warren , Cellular Confocal Fluorescence Studies of the Cytotoxic Activity of New Zn(II) Bisthiosemicarbazonato Complexes Dalton Trans., 2008, 2107.
3. S. I. Pascu*, P. A. Waghorn , T. D. Conry, H. M. Betts, J. R. Dilworth, G. C. Churchill, T. Pokrovska, M. Christlieb , F. I. Aigbirhio, J. E. Warren , Designing Zn(II) and Cu(II) derivatives as probes for in vitro fluorescence imaging Dalton Trans., 2007, 4988.
4. S. I. Pascu *, C. Naumann , Guido Kaiser, Andrew Bond, J. K. M. Sanders, T. Jarrosson, Structures and solution dynamics of cation-mediated pseudorotaxanes Dalton Trans.,2007, 3874.
5. Z. Rodriguez-Docampo, S. I. Pascu, S. Kubik, and S.Otto, Noncovalent interactions within a synthetic receptor can reinforce guest binding J. Am. Chem. Soc., 2006, 128(34), 11206.
6. L. H. Tong, S. I. Pascu, T. Jarrosson, and J. K. M. Sanders, Large-scale synthesis of alkyne-linked tripodal porphyrins via Palladium-mediated coupling conditions Chem. Commun., 2006, 1085.
7. A. L. Kieran, S. I. Pascu, T. Jarrosson, M. J. Gunter and J. K. M. Sanders , Dynamic synthesis of a macrocycle containing a porphyrin and an electron donor Chem. Commun., 2005, 1842.
8. A. L. Kieran, S. I. Pascu, T. Jarrosson, and J. K. M. Sander Inclusion of C₆₀ into an adjustable porphyrin dimer generated by dynamic disulfide chemistry Chem. Commun., 2005, 1276.
9. S. I. Pascu, T. Jarrosson, C. Naumann, S. Otto, J. K. M. Sanders Cation-reinforced donor-acceptor pseudorotaxanes New J. Chem., 2005, 80.
10. S. L. J. Conway, M. L. H. Green*, S. I. Pascu* and H. O. Peake Structure-reactivity correlations in new W(IV) and Nb(IV) silicon-bridged ansa-metallocene hydrides Polyhedron 2005, 25, 406.
11. J. R. Dilworth, C. A. Maresca von Beckh W. and S. I. Pascu Synthesis, Structures and Catalysis of Thioether-Phosphane Complexes of Pd(II) and Pt(II) Dalton Trans., 2005, 2151.
12. S. I. Pascu*, K. S. Coleman, A. R. Cowley, M. L. H. Green* and N. L. Rees New Cationic Palladium(II) and Rhodium(I) Complexes of [Ph₂PCH₂C(Ph)=N(2,6-Me₂C₆H₃)] J. Organomet. Chem., 2005, 690, 1645.
13. G. D. W. Anderson, O. J. Boys, A. R. Cowley, J. C. Green, M. L. H. Green, S. A. Llewellyn, C. Maresca von Beckh, S. I. Pascu, I. C. Vei Structural Investigations on New Iron-acyl Derivatives of B(C₆F₅)₃ J. Organomet. Chem., 2004, 689, 4407.
14. I. C. Vei, S. I. Pascu, M. L. H. Green, J. C. Green, R. E. Schilling, G. D. W. Anderson, L. H. Rees Synthesis and study of binuclear compounds containing bridging (m-CN)B(C₆F₅)₃ and (m-NC)B(C₆F₅)₃ systems Dalton Trans., 2003, 2550.