DOTA(allyl ester)3

The synthesis of a new nonacoordinating ligand based on an AMPED (6-amino-6-methylperhydro-1,4-diazepine) scaffold functionalized by three picolinate (6-carboxy-2-methylpyridine) arms is described. Coordination of lanthanide cations (Ln = Eu and Tb) was investigated by spectrophotometric titrations monitored by UV-Vis absorption and steady-state emission spectroscopy, showing the formation of [LnL] complexes in aqueous solutions. The corresponding Eu and Tb complexes were isolated and characterized, and their spectroscopic properties (luminescence quantum yields, excited state lifetimes) were determined in buffered water (TRIS/HCl, pH 7.4) and compared to the data reported in the literature for related systems. DFT modelling of the complexes showed the picolinate arms to be perfectly wrapped around the Ln(3+) cations, affording an excellent shielding of the metal as confirmed by the determination of the hydration number of q = 0 for both complexes. The high resolution emission spectrum was used to determine the radiative lifetime of Eu in the complex (τrad = 3.05 ms) and the metal-centred luminescence quantum yield (0.20). The modest 0.10 overall luminescence quantum yield of the Eu complex is a consequence of an energy transfer with medium efficiency (0.50) and a low metal centred luminescence efficiency attributed in part to the presence of numerous NH and CH bonds in close proximity to the metal centre.

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ↔ Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.

The interest in ratiometric luminescent probes that detect and quantify a specific analyte is growing. Owing to their special luminescence properties, lanthanide(III) cations offer attractive opportunities for the design of dual-color ratiometric probes. Here, the design principle of hetero-bis-lanthanide peptide conjugates by using native chemical ligation is described for perfect control of the localization of each lanthanide cation within the molecule. Two zinc-responsive probes, r-LZF1Tb|Cs124|Eu and r-LZF1Eu|Cs124|Tb are described on the basis of a zinc finger peptide and two DOTA (DOTA=1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) complexes of terbium and europium. Both display dual-color ratiometric emission in response to the presence of Zn2+ . By using a screening approach, anthracene was identified for the sensitization of the luminescence of two near-infrared-emitting lanthanides, Yb3+ and Nd3+ . Thus, two novel zinc-responsive hetero-bis-lanthanide probes, r-LZF3Yb|Anthra|Nd and r-LZF3Nd|Anthra|Yb were assembled, the former offering a neat ratiometric response to Zn2+ with emission in the near-infrared around 1000 nm, which is unprecedented.