Lanthanide complexes of macrocyclic derivatives useful for medical applications*
Rita Delgado1,2, Judite Costa3, Krassimira P. Guerra1, and Luís M. P. Lima1
1Instituto de Tecnologia Química e Biológica, UNL, Apartado 127, 2781-901 Oeiras, Portugal; 2Instituto Superior Técnico, Dep. de Química, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; 3Fac. de Farmácia da Universidade de Lisboa, Av. das Forças Armadas, 1649-019 Lisboa, Portugal
Abstract: The protonation constants of two series of tetraazamacrocyclic ligands with acetate and methylphosphonate pendant arms, as well as their stability constants with Cu2+, La3+, Sm3+, and Ho3+, were determined. All the values were determined in aqueous solution at 298.0 K and 0.10 mol dm–3 in N(CH3)4NO3. In the first series, the effect of both types of pendant arms was observed by appending them in the same macrocyclic backbone, a 14‑membered tetraazamacrocycle containing pyridine (ac3py14, p2py14, and p3py14). In the second series, two effects were taken into account, the increase of the cavity size of the macrocycle, from 12- to 14-membered, and the appending of acetate (dota, trita, and teta) or methylphosphonate (dotp, tritp, and tetp) arms. The ligands containing methylphosphonate arms have higher thermodynamic stability compared to the corresponding ones with acetate arms, especially in the series of compounds containing pyridine, even upon correction of the different basicity values of the ligands. On the other hand, the ligands with smaller macrocyclic cavity size, namely, dota and dotp, exhibit the largest values of stability constants. In contrast, ac3py14 presents low stability constants with lanthanides. An interpretation of these features based on the known adopted arrangement of dota and teta when free or coordinated with lanthanides is evaluated.
Keywords: stability constants; tetraazamacrocycles; lanthanide ions; methylphosphonate derivatives; acetate derivatives; speciation; metal complexes.
*Paper based on a presentation at the 11th International Symposium on Solubility Phenomena (11th ISSP), Aveiro, Portugal, 25-29 July 2004. Other presentations are published in this issue, pp. 513-665.