Critical evaluation of five emissive europium(iii) complexes as optical probes: correlation of cytotoxicity, anion and protein affinity with complex structure, stability and intracellular localisation profile

Abstract

Five structurally related europium(III) complexes of heptadentate macrocyclic ligands bearing azaxanthone or azathiaxanthone chromophores have been evaluated comparatively as responsive probes of the intracellular environment. Protein binding (HSA) and oxy-anion binding constants have been measured by titrimetric analysis, examining ratiometric emission changes for three examples, and systems exhibiting selectivity for citrate or hydrogencarbonate identified. The cytotoxicity of each ligand and complex has been assessed and correlated with the observed chemical stability profile in competitive aqueous media. The europium complex of L² is non-toxic, exhibits a large change in its emission spectral profile to variation in HCO₃⁻ (or citrate) concentration allowing ratiometric analysis, and localises in cellular mitochondria. Such features augur well for its future application as a responsive probe in microscopy to monitor local changes in pHCO₃.