Design, synthesis and application of luminescent rhenium complexes in cell imaging
Fernandez Moreira, Vanesa
This thesis describes the development of a new variety of lumophores, in particular luminescent rhenium(I) complexes of the type Re(bisim)(CO)3L n+, where bisim represents a bisimine derivative, e.g. bipyridine, and Lisa pyridine derivative (n = 1) or a chloride (n = 0), suitable for specific cell imaging and whose modified photophysical properties overcome some of the problems associated with traditional imaging agents (small Stokes shift, short lifetimes, etc). Specifically the successful synthesis and photophysical studies of a chemical model to validate the concept of a membrane permeable cell-imaging device, fac-Re0)ipyXCO)3(PyCH2COO(CH2)3OTBD) +, are presented. Further investigations towards and improved cell imaging agent, considering different issues like water solubility, lipophilicity and cell encapsulation rate, are then undertaken. Consequently, a new range of water soluble rhenium complexes, ykc- Re(bisimXCO)3(L) n" where bisim is a water soluble bathophenanthroline and L is a pyridine derivative (n = 2) or a chloride (n = 1), as well as a variety of novel yac-Re(bisimXCO)3Cl complexes, where bisim is a terpyridine derivative bearing a self destruction device which can be triggered by nitroreductase, are also presented. Additionally, the synthesis and structural description of a trinuclear rhenium complex is reported, along with a discussion of its use in inclusion experiments and attempts at analogue formation. The design and synthesis of a thiol selective luminescent rhenium complex, fac-Re(bipyXCO)3(PyCH2Cl) +, is described, along with the demonstration of its thiol selectivity both in vitro and in vivo as demonstrated by specific mitochondrial localization. Finally, studies of membrane permeability in liposome models, cellular uptake and localization in different cells such as Spironucleous vortens, yeast cells and human breast cancer cells of a variety of rhenium complexes above cited are also reported. These results combine to demonstrate the promising future of this new class of imaging probes as specific cell imaging agents and therefore, this work represents the initial step in the growing area of the development of transition metal based imaging agents.
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