Steric and Geometric Tuning of π-Conjugated Antennae in Europium(III) Complexes for Selective ADP Recognition

Abstract

The selective recognition of adenosine diphosphate (ADP) in water presents a significant challenge for synthetic supramolecular chemistry, driven by its biological importance in cellular energy transfer and enzymatic signaling pathways. Discriminating ADP from structurally similar anions such as ATP requires a high degree of host-guest complementarity. We recently developed [Eu.ADPGlow]^-, a luminescent Eu(III) complex bearing two 6-substituted quinolyl-phenoxyacetate arms, which create a binding site at the central Eu(III) ion that accommodates ADP. Binding induces a tight interaction in water, involving both metal coordination and π-π stacking, switching the emission on with a 33-fold enhancement. Here, we examine how systematic changes in ligand geometry influence anion selectivity, by synthesizing four new Eu(III) complexes with pendant arms at the 4- or 7-positions of the quinoline scaffold. The 4-substituted systems provide a more accessible binding site and bind ADP, ATP, and AMP with limited selectivity between them, while the 7-substituted analogues impose steric hindrance at the Eu(III) center, resulting in minimal response to all tested anions. Only the 6-substituted complex [Eu.ADPGlow]^- achieves optimal geometrical complementarity for ADP binding. These findings reinforce the importance of steric and geometric control in the design of selective lanthanide probes for biological anions in water.

Keywords: anion receptor; europium; host‐guest recognition; lanthanide probe; luminescent probe.

Figure 1

(left) Structures of the previously reported probes [Eu.6PhOMe]⁺ and [Eu.ADPGlow]⁻; (right) Structures of the novel regioisomeric probes presented in this work, designed to identify the optimal steric and geometric features for selective ADP binding.

Scheme 1

Synthesis of complexes [Eu.4PhOMe]⁺ and [Eu.4PhOCH₂COO]⁻.

Figure 2

Single crystal X‐ray structure of [Eu.4PhOMe]⁺ viewed a) perpendicular to the b axis and b) along the main pseudo‐C2 axis. The hydrogen atoms of the coordinating water molecule are shown, all other hydrogen atoms, non‐coordinating water molecules, and the triflate counter ion have been omitted for clarity. Only the major macrocycle conformation is shown; the lowest occupancy disorder component has been omitted. Atom colors: Eu green, C gray, N blue, O red, H white.

Figure 3

a) Single crystal X‐ray crystal structure of [Eu.7PhOMe]⁺, displaying the carboxylate coordination to Eu1 and the twisted geometry of Eu2 along the main pseudo‐C2 axis. The hydrogen atoms, noncoordinating water molecules and counter ions have been omitted for clarity. The lowest occupancy disorder component has also been omitted. Atom colors: Eu green, C gray, N blue, O red.

Figure 4

¹H NMR spectra (500 MHz, CD₃OD) of [Eu.4PhOMe]⁺ (green), [Eu.6PhOMe]⁺ (blue), and [Eu.7PhOMe]⁺ (black) recorded at 298 K. The spectrum of complex [Eu.6PhOMe]⁺ was reproduced from previous work.^{[ 30 ]}

Figure 5

a) Absorption spectra of Eu(III) complexes in methanol at 295 K, showing a progressive red‐shift in absorption maxima as the conjugated substituents move from the 4‐ to 6‐ to 7‐position of the quinoline ring. b) Emission spectra of methoxyphenyl‐substituted Eu(III) complexes, measured in methanol at 0.1 Abs and 295 K.

Figure 6

Emission spectra of a) [Eu.4PhOCH₂COO]⁻ (λ _exc 321 nm), b) [Eu.ADPGlow]⁻ (λ _exc 337 nm), and c) [Eu.7PhOCH₂COO]⁻ (λ _exc 350 nm), measured in methanol.

Figure 7

a) Emission spectra of the water‐soluble Eu(III) complexes (0.1 Abs) [Eu.4PhOCH₂COO]⁻ (λ _exc 321 nm), [Eu.ADPGlow]⁻ (λ _exc 337 nm), and [Eu.7PhOCH₂COO]⁻ (λ _exc 350 nm), measured in 10 mM HEPES buffer at pH 7.0, 295 K. b) pH titration of [Eu.7PhOCH₂COO]⁻ showing the increase in emission intensity upon incremental addition of NaOH, where the pH was adjusted ∼0.5 pH unit. c) Plot of intensity of the ΔJ = 2 emission band as a function of pH, showing the fit to the experimental data for [Eu.7PhOCH₂COO]⁻. Measured in water, 295 K, 0.1 Abs, λ _exc 350 nm.

Figure 8

Selective emission enhancement of the ΔJ = 2 (605 – 630 nm) of a) [Eu.4PhOCH₂COO]⁻ (0.1 Abs, λ _exc 321 nm), b) [Eu.ADPGlow]⁻ (0.1 Abs, λ _exc 337 nm), and c) [Eu.7PhOCH₂COO]⁻ (0.1 Abs, λ _exc 350 nm), with acetate, lactate, sulfate, nitrate, citrate, bicarbonate, phosphate, pyrophosphate (PPi), adenosine monophosphate (AMP), ADP, ATP, and cyclic adenosine monophosphate (cAMP) (1 mM each).