Coordination compounds of the lanthanide ions (Ln(3+)) have important applications in medicine due to their photophysical, magnetic, and nuclear properties. To effectively use the Ln" ions for these applications, chelators that stably bind them in vivo are required to prevent toxic side effects that arise from localization of these ions in off-target tissue. In this study, two new picolinate-containing chelators, a heptadentate ligand OxyMepa and a nonadentate ligand Oxyaapa, were prepared, and their coordination chemistries with Ln(3+) ions were thoroughly investigated to evaluate their suitability for use in medicine. Protonation constants of these chelators and stability constants for their Ln(3+) complexes were evaluated. Both ligands exhibit a thermodynamic preference for small Ln(3+) ions. The log K-LuL = 12.21 and 21.49 for OxyMepa and Oxyaapa, respectively, indicating that the nonadentate Oxyaapa forms complexes of significantly higher stability than the heptadentate OxyMepa. X-ray crystal structures of the Lu3+ complexes were obtained, revealing that Oxyaapa saturates the coordination sphere of Lu3+, whereas OxyMepa leaves an additional open coordination site for a bound water ligand. Solution structural studies carried out with NMR spectroscopy revealed the presence of two possible conformations for these ligands upon Ln(3+) binding. Density functional theory (DFT) calculations were applied to probe the geometries and energies of these conformations. Energy differences obtained by DFT are small but consistent with experimental data. The photophysical properties of the Eu3+ and Tb3+ complexes were characterized, revealing modest photoluminescent quantum yields of <2%. Luminescence lifetime measurements were carried out in H2O and D2O, showing that the Eu3+ and Tb3+ complexes of OxyMepa have two inner-sphere water ligands, whereas the Eu3+ and Tb3+ complexes of Oxyaapa have zero. Lastly, variable-temperature O-17 NMR spectroscopy was performed for the Gd-OxyMepa complex to determine its water exchange rate constant of k(ex)(298) = (2.8 +/- 0.1) X 10(6) s(-1). Collectively, this comprehensive characterization of these Ln(3+)( )chelators provides valuable insight for their potential use in medicine and garners additional understanding of ligand design strategies.