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Three dipicolinic acid amine-derived compounds functionalized with a carboxylate (Hdpaa), phosphonate (Hdppa), and bisphosphonate (Hdpbpa), as well as their nonfunctionalized analogue (Hdpa), were successfully synthesized and characterized. The 1:1 lanthanum(III) complexes of Hdpa, Hdpaa, and Hdppa, the 1:2 lanthanum(III) complex of Hdpa, and the 1:1 gallium(III) complex of Hdpaa were characterized, including via X-ray crystallography for [La(dppa)(HO)] and [Ga(dpaa)(HO)]. Hdpa, Hdpaa, and Hdppa were evaluated for their thermodynamic stability with lanthanum(III) via potentiometric and either UV-vis spectrophotometric (Hdpaa) or NMR spectrometric (Hdpa and Hdppa) titrations, which showed that the carboxylate (Hdpaa) and phosphonate (Hdppa) containing ligands enhanced the lanthanum(III) complex stability by 3-4 orders of magnitude relative to the unfunctionalized ligand (comparing log β and pM values) at physiological pH. In addition, potentiometric titrations with Hdpaa 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 P 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 Ga, radiolabeling studies were performed withGa and Hdpaa. Quantitative radiolabeling was achieved at pH 6.5 in 10 min at room temperature with concentrations as low as 10 M, and human serum stability studies were undertaken.

This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10 antineoplastic drugs (5-fluorouracil, oxaliplatin, methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine, docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of this method along with the comparatively short run time (8 min) allows for its use in routine monitoring in health care facilities. The long-term behavior of the studied drugs on contaminated surfaces and the effect of surface roughness on drug recoveries were studied to gain insights about how these environmental variables influence the detection, cleaning, and occupational exposure of these drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the lowest recoveries while those with lower Ra (smoother) presented the highest recoveries. Long-term assessments evidence distinctive drug behaviors with oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most persistent drugs with recoveries of 40% and 80% after 1 month. This information indicates the importance of collecting ancillary information about drug usage (throughput, timing, cleaning procedures, etc.) to interpret the results in the context of potential exposure. Finally, the method was successfully applied to evaluate trace surface contamination down to the single picogram per square centimeter in multiple work areas within three local health care centers on Vancouver Island, Canada.