The equilibria for core Ca(2+) replacement by Ln(3+) in copper(II) 15-MC-5 complexes have been investigated using a series of visible spectrophotometric titrations of calcium(II) metallacrowns ({Ca(II)[15-MC(Cu(II)(N)(L))-5]}(2+)) with Ln(3+) ions (H(2)L = pheha, (S)-alpha-phenylalaninehydroxamic acid, or trpha, (S)-alpha-tryptophanhydroxamic acid). These studies allowed the determination of the equilibrium constants for the reaction {Ca(II)[15-MC(Cu(II)(N)(L))-5]}(2+) + Ln(3+) --> {Ln(III)[15-MC(Cu(II)(N)(L))-5]}(3+) + Ca(2+) in methanol/water 9:1 (Ln(3+) = La(3+), Gd(3+), Dy(3+), Er(3+)) or 99:1 (Ln(3+) = La(3+), Nd(3+), Gd(3+), Dy(3+), Er(3+), Yb(3+)), respectively. The log K for these reactions decreases with increasing atomic number of the lanthanide(III), ranging from 6.1 to 3.91 in methanol/water 9:1. The same behavior is observed in methanol/water 99:1, although the constants are uniformly lower (log K = 4.09-2.52). A significant thermodynamic selectivity was observed for the later lanthanides (Gd(3+)-Yb(3+)) while a smaller selectivity is present throughout the beginning of the series (La(3+)-Gd(3+)). This observation has been interpreted on the basis of the size correspondence between the metal ions and the metallacrown cavity. The overall stability of the {Ca(II)[15-MC(Cu(II)(N)(L))-5]}(2+) in methanol/water 9:1 has been determined by pH-spectrophotometric titrations with HCl. The resulting log K values are 63.46(12) and 65.05(13) for pheha and trpha, respectively (Ca(2+) + 5Cu(2+) + 5HL(-) = {Ca(II)[15-MC(Cu(II)(N)(L))-5]}(2+) +5H(+)). The stability of both the La(3+) and Ca(2+) 15-metallacrown-5 complexes in the presence of high Na(+) concentrations has also been demonstrated by spectophotometric studies. Based upon these observations, the preference of the 15-MC-5 for Ca(2+) complexation compared to crown ethers has been quantitatively demonstrated for the first time.