Responsive luminescent lanthanide probes for biological applications

Abstract

Lanthanide-based complexes play a significant role in biological applications,
spanning MRI contrast agents to molecular luminescent tags. Regardless of their
application, these complexes should conform to general requirements, such as high stability against decomplexation at physiologically relevant conditions and sufficient solubility in water. Other more specific requirements may also apply, demanding a customised design of the ligand for a specific application.

Emissive bio-responsive lanthanide complexes comprise a large and dynamically
developing area, which possesses several intrinsic advantages over non-lanthanide analogues. Large Stokes’ shifts, long-lived excited states, ratiometric bands in the emission spectrum, strong cirularly-polarised signals are but a few to be named. These beneficial properties can be employed for efficient measurement of pH or determination of bioactive molecules both in vitro and in cellulo. For instance, europium complexes bearing sulphonamide arms showed reversible pH-response, producing noticeable changes in both the total emission and CPL spectra (Chapter 2). Other europium complexes possessing polarity-sensitive emission intensity were successfully used for detection of human serum albumin and α1-AGP – two the most abundant serum proteins – by following both total emission and CPL spectra, and these results are discussed in Chapter 3.

Selective detection of biologically relevant anions needs specific probe design
requirements. Even subtle changes in the structure of the ligand may lead to
considerable changes in selectivity and affinity towards selected species. Such a
correlation between structure and binding properties was exemplified in a series of
europium complexes for the detection of nucleotides and zinc and led to the creation of probes spanning 5 orders of affinity constants. Furthermore, a nucleotide-specific induced CPL signal allowed monitoring the ratio between ADP and ATP – a parameter that characterises metabolic rates in mitochondria. These observations are thoroughly analysed in Chapter 4.