Three dipicolinic acid amine-derived compounds functionalized with a carboxylate (H3dpaa), phosphonate (H4dppa), and bisphosphonate (H7dpbpa), as well as their nonfunctionalized analogue (H2dpa), were successfully synthesized and characterized. The 1:1 lanthanum(III) complexes of H2dpa, H3dpaa, and H4dppa, the 1:2 lanthanum(III) complex of H2dpa, and the 1:1 gallium(III) complex of H3dpaa were characterized, including via X-ray crystallography for [La4(dppa)4(H2O)2] and [Ga(dpaa)(H2O)]. H2dpa, H3dpaa, and H4dppa were evaluated for their thermodynamic stability with lanthanum(III) via potentiometric and either UV-vis spectrophotometric (H3dpaa) or NMR spectrometric (H2dpa and H4dppa) titrations, which showed that the carboxylate (H3dpaa) and phosphonate (H4dppa) containing ligands enhanced the lanthanum(III) complex stability by 3-4 orders of magnitude relative to the unfunctionalized ligand (comparing log βML and pM values) at physiological pH. In addition, potentiometric titrations with H3dpaa and gallium(III) were performed, which gave significantly (8 orders of magnitude) higher thermodynamic stability constants than with lanthanum(III). This was predicted to be a consequence of better size matching between the dipicolinate cavity and gallium(III), which was also evident in the aforementioned crystal structures. Because of a potential link between lanthanum(III) and osteoporosis, the ligands were tested for their bone-directing properties via a hydroxyapatite (HAP) binding assay, which showed that either a phosphonate or bisphosphonate moiety was necessary in order to elicit a chemical binding interaction with HAP. The oral activity of the ligands and their metal complexes was also assessed by experimentally measuring log Po/w values using the shake-flask method, and these were compared to a currently prescribed osteoporosis drug (alendronate). Because of the potential therapeutic applications of the radionuclides 67/68Ga, radiolabeling studies were performed with 67Ga and H3dpaa. Quantitative radiolabeling was achieved at pH 6.5 in 10 min at room temperature with concentrations as low as 10-5 M, and human serum stability studies were undertaken.