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 Angstrom, b = 22.504 Angstrom, c = 23.975 Angstrom, and beta = 97.05 degrees). The Eu3+ cation is bound to four macrocyclic nitrogen atoms (mean Eu-N = 2.627 Angstrom) and four amide oxygen atoms (mean Eu-O-amide = 2.335 Angstrom) in a square antiprismatic geometry with a twist angle of 38.5 degrees between the N4 and O4 planes. A single bound water molecule (Eu-O-W = 2.414 Angstrom) occupies a typical monocapped position on the O4 surface. In pure waters resonances corresponding to a single Eu3+-bound water molecule were observed in the H-1 (53 ppm) and O-17 (-897 ppm) NMR spectra of [Eu(4)(H2O)](triflate)(3) at 25 degreesC. A fit of the temperature-dependent Eu3+-bound H-1 and O-17 water resonance line widths in acetonitrile-d(3) (containing 4% v/v O-17 enriched water) gave identical lifetimes (tau (298)(m)) of 789 +/- 50 mus (in water as solvent; a line shape analysis of the Eu3+-bound water resonance gave a tau (298)(m) = 382 +/- 5 mus). Slow water exchange was also evidenced by the water proton relaxivity of Gd(4) (R-1 = 2.2 mM(-1) s(-1), a value characteristic of pure outer-sphere relaxation at 25 degreesC). 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 (T-1) to standard SBM theory gave a water proton lifetime (tau (298)(m)) of 159 mus, somewhat shorter than the value determined by high-resolution H-1 and O-17 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 degreesC (Ri increased to 10.0 m(-1) s(-1) in the presence of 1500-fold excess HPO42-).