Principles of responsive lanthanide-based luminescent probes for cellular imaging

Abstract

The advent of chemical tools for cellular imaging--from organic dyes to green fluorescent proteins--has revolutionized the fields of molecular biology and biochemistry. Lanthanide-based probes are a new player in this area, as the last decade has seen the emergence of the first responsive luminescent lanthanide probes specifically intended for imaging cellular processes. The potential of these probes is still undervalued by the scientific community. Indeed, this class of probes offers several advantages over organic dyes and fluorescent proteins. Their very long luminescence lifetimes enable quantitative spatial determination of the intracellular concentration of an analyte through time-gating measurements. Their emission bands are very narrow and do not overlap, enabling the simultaneous use of multiple lanthanide probes to quantitatively detect several analytes without cross-interference. Herein we describe the principles behind the development of this class of probes. Sensors for a desired analyte can be designed by rationally manipulating the parameters that influence the luminescence of lanthanide complexes. We will discuss sensors based on varying the number of inner-sphere water molecules, the distance separating the antenna from the lanthanide ion, the energies of excited states of the antenna, and PeT switches.

Interpretation of europium(III) spectra

“…Finally, the emission of the fast decaying species is eliminated and only the emission of the slowly decaying species remains. Time-gated spectroscopy is also useful to measure europium(III) spectra in biological samples, because the technique allows exclusion of the background fluorescence of the biological material [776][777][778][779][780][781][782]. Time-resolved detection of europium(III) forms the basis of several biomedical analyses and bioanalytical assays [33,93,[783][784][785][786].…”

Development of New Double-Stranded Phenylalanyl Chelators Using .ETA.-.CHI. Diagrams and Binding Constants for Chelators and Lanthanide Ions

“…In the diagram in Fig. 1a, the Cat (7) is a softer chelator than 18-crown-6-ether (2), en (3), ethylenediaminetetraacetic acid (EDTA) (4), 12-ane-4 (5), and calixarene (8) ions in solution; therefore, we designed and synthesized a novel chelator (1), in which a chemically soft ligand 7 was conjugated to two terminals in the molecule. Although the spacer -HN-CH 2 CH 2 -O-CH 2 CH 2 -O-CH 2 CH 2 -NH-of 1 is as chemically hard as ligand 2 or 5, 1 joined to 7 is a chemi- cally softer chelator than 7 or 8.…”

“…Lanthanides (Ln) as heavy rare earth elements and Y are attracting the interest of chemists since complexes prepared by the reaction of lanthanide ions (Ln 3ϩ ) with chelators have a variety of applications, including probes for fluorometry, [1][2][3][4] catalysts, 5) sensitizing chromophores, [6][7][8] and nanomaterials. 9,10) Recently, lanthanide ions with unique photophysical and coordination properties have been used to develop lanthanide-antenna sensors as luminescent sensors for cellular imaging, 8) and protein and DNA assays.…”

“…9,10) Recently, lanthanide ions with unique photophysical and coordination properties have been used to develop lanthanide-antenna sensors as luminescent sensors for cellular imaging, 8) and protein and DNA assays. As chemical and physicochemical properties, lanthanides are chemically similar to metal ions because of the shielding of progressively filled inner 4f orbitals by the filled outer 5s and 5p orbitals and the lanthanide contraction effect.…”

“…18,19) The chelator could expect flexible conformation due to a backbone conjugated with two amino acid residues to the N-terminus of a spacer, -O-CH 2 -CH 2 -O-, and its binding site is Cat, not an amido group. Chelator 1 provides a coordinate bond complex with Ln 3ϩ of the largest ionic radius in 10 mM N- (2-hydroxyethyl) Complexes of chelator 1 with Ln 3ϩ may be applied in the pharmacological field as chemotherapeutic agents and luminescent sensors, 8) which are a subject of many recent studies. In addition, the quantum chemical h-c diagram is a useful tool for the design of chelators, and we will deal with the synthesis and characterization of the complexes of the chelator with Ln 3ϩ .…”