Rigidified Derivative of the Non-macrocyclic Ligand H4OCTAPA for Stable Lanthanide(III) Complexation

Abstract

The stability constants of lanthanide complexes with the potentially octadentate ligand CHXOCTAPA^4-, which contains a rigid 1,2-diaminocyclohexane scaffold functionalized with two acetate and two picolinate pendant arms, reveal the formation of stable complexes [log K_LaL = 17.82(1) and log K_YbL = 19.65(1)]. Luminescence studies on the Eu³⁺ and Tb³⁺ analogues evidenced rather high emission quantum yields of 3.4 and 11%, respectively. The emission lifetimes recorded in H₂O and D₂O solutions indicate the presence of a water molecule coordinated to the metal ion. ¹H nuclear magnetic relaxation dispersion profiles and ¹⁷O NMR chemical shift and relaxation measurements point to a rather low water exchange rate of the coordinated water molecule (k_ex²⁹⁸ = 1.58 × 10⁶ s^-1) and relatively high relaxivities of 5.6 and 4.5 mM^-1 s^-1 at 20 MHz and 25 and 37 °C, respectively. Density functional theory calculations and analysis of the paramagnetic shifts induced by Yb³⁺ indicate that the complexes adopt an unprecedented cis geometry with the two picolinate groups situated on the same side of the coordination sphere. Dissociation kinetics experiments were conducted by investigating the exchange reactions of LuL occurring with Cu²⁺. The results confirmed the beneficial effect of the rigid cyclohexyl group on the inertness of the Lu³⁺ complex. Complex dissociation occurs following proton- and metal-assisted pathways. The latter is relatively efficient at neutral pH, thanks to the formation of a heterodinuclear hydroxo complex.

Chart 1. Ligands Discussed in the Present Work

Figure 1

Relaxometric titrations (25 °C, 0.15 M NaCl) of the [Gd(CHXOCTAPA)]⁻ complex with LaCl₃ (squares, c_Lig = c_Gd3+ = 1.001 mM at pH = 4.69), YbCl₃ (circles, c_Lig = c_Gd3+ = 1.113 mM at pH = 4.79), and ZnCl₂ (triangles, c_Lig = c_Gd³⁺ = 1.001 mM at pH = 4.81). All solutions were buffered using 50 mM DMP. The solid lines show the fit of the data for stability constant determination.

Figure 2

Emission spectra of the Eu³⁺ complexes with CHXOCTAPA^4– (blue solid line) and OCTAPA^4– (green dashed line) recorded in H₂O solution at pH 7.1 (λ_ex = 279 nm; absorption and emission slits 1 nm, 10^–4 M).

Figure 3

Top: Structures of the two isomers of [Gd(CHXOCTAPA) (H₂O)]⁻·2H₂O (second-sphere water molecules omitted for clarity) and relative energies calculated across the lanthanide series for the complexes with CHXOCTAPA^4– and OCTAPA^4–. Bottom: ¹H NMR spectrum of the Ce³⁺ complex recorded in D₂O solution (300 MHz, 25 °C, pH 7.0). Asterisks denote a minor species present in solution.

Figure 4

¹H NMR spectrum of [Yb(CHXOCTAPA)]⁻ (300 MHz, 25 °C, pH 7.0) and plot of the calculated chemical shifts versus those obtained with eq 1 and the structure of the cis isomer. The line represents the identity line.

Figure 5

Top: ¹H NMRD profiles recorded at different temperatures for [Gd(CHXOCTAPA)]⁻ (pH 7.27). Bottom: Reduced transverse (green ■) and longitudinal (red ▲) ¹⁷O NMR relaxation rates and ¹⁷O NMR chemical shifts (blue ●) measured for [Gd(CHXOCTAPA)]⁻ at 9.4 T (0.0199 mM, pH = 7.27). The lines represent the fit of the data as explained in the text.

Figure 6

Plot of the pseudo-first-order rate constants measured for the [Lu(CHXOCTAPA)]⁻ as a function of H⁺ ion concentration (50 mM DMP, 25 °C, 0.15 M NaCl) using different metal ion excess [10× (5.53 mM), 20× (11.07 mM), 30× (16.60 mM), and 40× (22.14 mM) was applied with pH = 3.30, 3.50, 3.80, 4.17, and 4.49]. The solid lines represent the fits of the data to eq 7.