Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I)

Abstract

The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I).

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

“…Starting materials such as anhydrous solvents, dimethyl 4-hydroxypyridine-2,6-dicarboxylate (TCI Europe) and 4,13-diaza-18-crown-6 (Merck) were purchased and used as received. Methyl 6-(chloromethyl)picolinate was prepared according to the literature [ 44 ].…”

New Coumarin Dipicolinate Europium Complexes with a Rich Chemical Speciation and Tunable Luminescence

“…All the intermediate compounds were characterized by 1 H-and 13 C-NMR and the two ligands HL 1 and HL 2 , and the two tris complexes Na 3 [Eu(L 1 ) 3 ] and Na 3 [Eu(L 2 ) 3 ] were fully characterized by 1 H-and 13 C-NMR, high resolution mass spectrometry (HRMS) and their purities assessed by HPLC at 254 nm (purity > 95% for all the target compounds) and by elemental analysis for the two target complexes.…”

“…Coumarin-based probes are known to be incredibly versatile systems with photophysical properties dynamically modulated by a large set of boundary conditions (pH, polarity, viscosity, specific analyte) [ 7 , 8 , 9 , 10 ]. However, their use as a lanthanide sensitizer has been limited to just a few examples [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]: of note, those cases where the coumarin antenna directly coordinates the lanthanide ion are usually characterized by poorly stable complexes with limited application [ 11 , 14 , 21 ], whereas in all the other examples the absence of a tight connection with the metal ion greatly hampers the efficiency of the sensitization process (i.e., low quantum yields) [ 12 , 15 , 16 , 18 , 19 , 20 , 22 , 23 , 24 ]. Moreover, coumarin-based lanthanide complexes, due to the antenna intrinsic photophysical properties, usually display contemporary emission of both the lanthanide ion and the coumarin fragment: although the dual emission is an intriguing feature considering possible applications, it is fundamental to conceive a system which can be easily modified to finely tune the emission properties.…”

“…Coumarin-based probes are known to be incredibly versatile systems with photophysical properties dynamically modulated by a large set of boundary conditions (pH, polarity, viscosity, specific analyte) [7][8][9][10]. However, their use as a lanthanide sensitizer has been limited to just a few examples [11][12][13][14][15][16][17][18][19][20][21][22][23][24]: of note, those cases where the coumarin antenna directly coordinates the lanthanide ion are usually characterized by poorly stable complexes with limited application [11,14,21], whereas in all the other examples the absence of a tight…”

A Genetically Encoded Picolyl Azide for Improved Live Cell Copper Click Labeling

“…Installation of the requisite azide functionality was effected using a one-pot process where the hydroxyl group of 5 was converted into the corresponding alkyl bromide (PPh 3 and CBr 4 ), followed by displacement with sodium azide without isolation of the bromide intermediate. Subsequent ester hydrolysis under basic conditions afforded carboxylic acid 7 ( Hanna et al, 2017 ). With building blocks 3 and 7 in hand, amide formation was performed using standard conditions (EDCI, HOBt, DIPEA in DMF).…”