Platinum Complexes as Imaging Agents in Live Cells

The development of novel phosphorescent materials has received attracting interest in the past decade. Luminescent platinum complexes are used in Organic Light Emitting Devices (OLEDs) as well as sensors. The square planarity renders these complexes also relevant for biomedical applications. Since the emerging unprecedented success of cis-Pt(NH3 ) 2 Cl 2 (cisplatin) as an anticancer agent, platinum(II) complexes are known to act as potential DNA- intercalation agents. Williams et al. have recently demonstrated that compounds based on the Pt(N^C^N) structure (N^C^N = 1,3-di(2-pyridyl)benzene) could offer potential as photoluminescent probes and imaging agents for use in live cells. The use of phosphorescent materials opens up the possibility of monitoring biodistribution and cell processes on the basis of lifetimes. In this work, the synthesis and characterisation of N^C^N-coordinated platinum(II) complexes is described. Derivatives carrying substituents on C5 position of the central phenyl ring have been found to be highly emissive, whilst allow tuning of the colour over a wide range from green-blue to orange. The photoluminescence quantum yields are amongst the very highest ever reported for platinum group metal complexes (up to 85% in solution at 293K) with luminescence lifetimes of the order of 5-10 µs; at room temperature. Starting with the synthesis and characterisation of novel tetradentate platinum complexes, the work aims to explore functionalised complexes for conjugating to biomolecules to exploit them as imaging agents for use in live cells. In order to direct the platinum(II) complexes to specific cell types within a multicellular organism, mild methods of for linking the emissive complex to appropriate groups (i.e. small peptides, antibody fragments) will be developed. Following the synthetic work and characterisation of new complexes, the photophysical properties will be investigated in detail, using a combination of steady-state and time-resolved emission spectroscopy. The cellular localisation of representative compounds will be screened by means of fluorescence microscopy. The objective will be to build up an empirical picture of the relationship between molecular structure, cellular uptake pathways and biodistribution.