¹H and ¹⁷O NMR detection of a lanthanide-bound water molecule at ambient temperatures in pure water as solvent

Lanthanide complexes of a tetra-amide derivative of DOTA (structure 4 in text) with four extended carboxymethyl esters have been characterized by X-ray crystallography and multinuclear NMR spectroscopy. [Eu(4)(H₂O)](triflate)₃ crystallized from water in the monoclinic, P_21/c space group (a = 10.366 Å, b = 22.504 Å, c = 23.975 Å, and β = 97.05°). The Eu³⁺ cation is bound to four macrocyclic nitrogen atoms (mean Eu-N = 2.627 Å) and four amide oxygen atoms (mean EU-O_amide = 2.335 Å) in a square antiprismatic geometry with a twist angle of 38.5° between the N4 and O4 planes. A single bound water molecule (Eu-O_w = 2.414 Å) occupies a typical monocapped position on the O4 surface. In pure water, resonances corresponding to a single Eu³⁺-bound water molecule were observed in the ¹H (53 ppm) and ¹⁷O (-897 ppm) NMR spectra of [Eu(4)(H₂O)](triflate)₃ at 25 °C. A fit of the temperature-dependent Eu³⁺-bound ¹H and ¹⁷O water resonance line widths in acetonitrile-d₃ (containing 4% v/v ¹⁷O enriched water) gave identical lifetimes (τ_m²⁹⁸) of 789 ± 50 μs (in water as solvent; a line shape analysis of the Eu³⁺-bound water resonance gave a τ_m²⁹⁸ = 382 ± 5 μs). Slow water exchange was also evidenced by the water proton relaxivity of Gd(4) (R₁ = 2.2 mM^-1 s^-1, a value characteristic of pure outer-sphere relaxation at 25 °C). With increasing temperature, the inner-sphere contribution gradually increased due to accelerated chemical exchange between bound water and bulk water protons. A fitting of the relaxation data (T₁) to standard SBM theory gave a water proton lifetime (τ_m²⁹⁸) of 159 μs, somewhat shorter than the value determined by high-resolution ¹H and ¹⁷O NMR of Eu(4). Exchange of the bound water protons in Gd(4) with bulk water protons was catalyzed by addition of exogenous phosphate at 25 °C (R₁ increased to 10.0 mM^-1 s^-1 in the presence of 1500-fold excess HPO₄^2-).