Thermodynamics of Self-assembly of Copper(II) 15-metallacrown-5 of Eu(III) and Gd(III) with (S)-α-Alaninehydroxamic Acid in Aqueous Solution

The equilibria of the ternary systems Cu(II)/ α-Alaha /Eu(III) or Gd(III) were studied in aqueous solution and the stability constants of two 15-MC-5, namely {Ln[Cu5L5H-5]}3+ and {Ln[Cu5L5H-5(OH)]}2+ , were determined. The Ln(III) distribution diagrams evidenced that the metallacrowns are the only species which contain the Ln3+ ions, suggesting that the metallamacrocyclic scaffold is obtained by direct self assembly of the ligand and the metal ions. Moreover, the speciation of these systems demonstrated the possibility for the 15-MC-5 and the 12-MC-4 complexes to coexist in solution as a function of the Ln:Cu:L molar ratios employed, and that the amount both types of MC complexes can be tuned with the pH. ESI-MS experiments performed as a function of pH and of various solvents allowed to find the most suitable conditions for the analysis of the MC in solution and to establish a possible correlation with the speciation diagrams. Finally, simulations based on the stability constants obtained for the 15-MC-5 complexes allowed us to critically re-evaluate on a quantitative ground a number of experimental observations concerning ligand- and metal-exchange processes for 15-MC-5 reported in the last decade. As a major point, it has been established that the Ln3+ metallacrowns are stable both with respect to competing ligands (either α-Alaha itself or EDTA and DOTA), and serum proteins like transferrin. Transmetallation processes involving Zn(II) to replace the encapsulated Ln3+ ions could be excluded, although the presence in solution of other components able to form very insoluble salts (such as phosphate) may affect the metallacrown integrity