Targeted Luminescent Europium Peptide Conjugates: Comparative Analysis Using Maleimide and para-Nitropyridyl Linkages for Organelle Staining

Abstract

The syntheses and photophysical behaviour of nine, strongly luminescent nonadentate Eu(III) complexes are reported. Each complex is based on N-functionalised 1,4,7triazacyclononane, and linkage to other groups or targeting vectors can occur either via amide bond formation to a coordinated pyridine p-aminopropyl group or via a nucleophilic substitution reaction involving thiol attack on a metal coordinated p-nitropyridyl moiety. Evidence is presented in favour of the latter conjugation strategy, as parallel work with maleimide conjugates was complicated or compromised by the propensity to undergo postconjugation thiol exchange or succinimide ring hydrolysis reactions. Confocal microscopy and spectral imaging studies revealed that the peptide conjugate of AcCFFKDEL was found to localise selectively in the endoplasmic reticulum of mouse fibroblast cells, whereas the related maleimide conjugate was only observed in cellular lysosomes.

Excited State Properties of Lanthanide(III) Complexes with a Nonadentate Bispidine Ligand

“…The equivalent emission spectra for solid state and solution experiments found for all three complexes, also suggest conservation of the symmetry upon solution of the complexes. The values for lifetimes and quantum yields are comparable to other well studied complexes with macrocylic ligands [3,6,12,24,25,28] …”

“…The values for lifetimes and quantum yields are comparable to other well studied complexes with macrocylic ligands. [3,6,12,24,25,28] The efficiency of the sensitization process could be further quantified in the case of the Eu III complex (see Supporting Information for details), where the radiative decay was calculated from the emission spectra to be 3.58 ms and 4.51 ms in the solid state and aqueous solution respectively. These numbers result in an intrinsic quantum yield of 0.41 and 0.34, respectively, giving sensitization efficiencies of 0.71 and 0.97, respectively.…”

“…The values for lifetimes and quantum yields are comparable to other well studied complexes with macrocylic ligands. [ 3 , 6 , 12 , 24 , 25 , 28 ]…”

“…[17][18][19] Quenching by the OÀ H overtones of water often occurs from coordinated H 2 O [20,21] but may also be due to H 2 O in the second coordination sphere, [22] and therefore, full encapsulation of the metal ions by the ligand is of great importance. Typical ligands used in the area are octa-and nonadentate macrocyclic [16,[23][24][25][26][27][28][29][30] and cryptate based ligands [5,8,31,32] as well as the tetradentate HOPO family [25,[33][34][35][36] and a ditopic ligand producing helicates, [37][38][39] as shown in Scheme 1, together with the published octadentate bispidine ligand L 1 [40,41] and its nonadentate derivative L 2 discussed here. Ln III ions often realize coordination numbers of 8 or 9.…”

Targeted pH switched europium complexes monitoring receptor internalisation in living cells

“…12 In addition, the simple pyridine group was functionalised with a primary amino-propyl group (N-Boc protected), in order to permit subsequent site-selective conjugation to different targeting vectors. 13 The synthesis of the Eu(III) complexes of L 1b and L 2a/2b was undertaken in a similar manner, (Scheme 1 and Scheme S2, ESI †), from mono-Boc-1,4,7-triazacyclononane. The syntheses involved a series of N-alkylation and simple deprotection steps, and the final complexes were purified by reverse phase HPLC.…”