Macrocyclic Receptor Exhibiting Unprecedented Selectivity for Light Lanthanides

Abstract

We report a new macrocyclic ligand, N,N'-bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6), designed for complexation of lanthanide ions in aqueous solution. Potentiometric measurements evidence an unprecedented selectivity of bp18c6 for the large Ln(III) ions. Among the different Ln(III) ions, La(III) and Ce(III) show the highest log K(ML) values, with a dramatic drop of the stability observed from Ce(III) to Lu(III) as the ionic radius of the Ln(III) ions decreases (log K(CeL) - log K(LuL) = 6.9). The X-ray crystal structures of the Gd(III) and Yb(III) complexes show that the metal ion is directly bound to the 10 donor atoms of the bp18c6 ligand. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by theoretical calculations performed at the DFT (B3LYP) level. Our results indicate that a conformational change occurs around the middle of the lanthanide series: for the larger Ln(III) ions the most stable conformation is Delta(deltalambdadelta)(deltalambdadelta), while for the smallest Ln(III) ions (Gd-Lu) our calculations predict the Delta(lambdadeltalambda)(lambdadeltalambda) form being the most stable one. This structural change was confirmed by the analysis of the Ce(III)-, Pr(III)-, and Yb(III)-induced paramagnetic (1)H shifts. The selectivity that bp18c6 shows for the large Ln(III) ions can be attributed to a better fit between the light Ln(III) ions and the relatively large crown fragment of the ligand. Indeed, our DFT calculations indicate that the interaction between the Ln(III) ion and several donor atoms of the crown moiety is weakened as the ionic radius of the metal ion decreases.

Stability and Toxicity of Contrast Agents

“…The large macrocyclic cavity combined with malonate or picolinate pendant arms (ligands ODDM and bp18c6) afforded large differences in the stability constants of the complexes formed with the light and heavy lanthanides (log K Ce(L) − log K Lu(L) = 5.4 for the ODDM and 6.9 for the bp18c6, Chart 4.7). This feature could potentially be exploited for the separation of the Ln 3+ ions [95,96].…”

An Eighteen‐Membered Macrocyclic Ligand for Actinium‐225 Targeted Alpha Therapy

“…[19] Furthermore,the 225 Ac-radiolabeling kinetics of this ligand are slow (see below), thus necessitating the application of heat if short labeling times are required. H 2 macropa was synthesized according to published procedures [23,24] and characterized by conventional techniques, including X-ray crystallography (see Figure S1, and Tables S1 and S2 in the Supporting Information). H 2 macropa was synthesized according to published procedures [23,24] and characterized by conventional techniques, including X-ray crystallography (see Figure S1, and Tables S1 and S2 in the Supporting Information).…”

Solvent Extraction Separation of Trivalent Americium from Curium and the Lanthanides

“…4). The stability constants of H 2 BP18C6 [28] and the lanthanide extraction constants of HDEHP and HEH[EHP] [43] suggest that the decreased intra-lanthanide selectivity observed for lanthanides heavier than Tb was due to the low stability of those Ln 3+ −BP18C6 2-complexes. Increasing the H 2 BP18C6 concentration in the system would improve the intra-lanthanide selectivity of the heaviest lanthanides.…”

“…The ligand H 2 BP18C6 was synthesized as previously described [28] with an additional purification step consisting of a heptane wash of an aqueous solution of the hydrochloride salt of H 2 BP18C6 followed by precipitation with acetone. The resulting material was analyzed using 1 H and 13 C NMR, mass spectrometry, potentiometric pH titration, and KarlFisher titration.…”

“…1), that could be used to separate Am(III) from Cm(III). [28,29] In a variation on the Downloaded by [New York University] at 12:21 03 August 2015 TALSPEAK process, we coupled H 2 BP18C6, which retains the larger Am 3+ cation in the aqueous phase, with the HDEHP, which preferentially extracts smaller f-element cations (both Cm 3+ and Ln 3+ heavier than Nd). With this combination of aqueous ligand and organic extractant, we observed single stage Cm/Am separation factors as high as 6.5, good selectivity for Am against lanthanides heavier than Pr when the aqueous pH was ca.…”