Design of luminescent lanthanide complexes for targeting DNA specific sites by X-ray structural investigation. 

Tumor cells are associated with the occurrence of mismatches in their DNA. Therefore, these mismatches can be considered as universal targets for the localization of these tumors. Ru(II) polypyridyl complexes have already attracted interest, due to their photophysical properties. These complexes do not show luminescence in water, but upon binding to DNA, their luminescence is ‘switched on’ (light-switching effect), which makes them suitable as DNA biosensors and agents in photodynamic tumor therapy (by DNA cleavage upon irradiation). Structural knowledge upon the binding modes of such complexes with DNA remained elusive until recently (august, 2012), the first two crystal structures of Ru(II) polypyridyl complexes, were reported by C. Cardin and J. Barton, independently, in the same high-impact journal Nature Chemistry and is considered as a new benchmark in the field. At the moment, no X-ray structures exist of lanthanide Ln(III) complexes bound to DNA. These complexes (e.g with Tb3+, Eu3+,…) have great advantage over Ru(II) complexes. For example, they can emit light in the near-infrared (NIR). As the human body is almost transparent for NIR, this would allow us to develop biosensors for deeply buried tumors. We propose to design novel Ln(III) complexes, and accumulate X-ray structures in order to elucidate their binding modes and mechanism of action and assess their luminescence properties, especially in the NIR region, in order to be applied in biomedical applications.