We have shown that the crown ether dicyclohexano-18-crown-6 recognizes the terminal amine group of deferriferrioxamine B (H4DFB+) and its Al(III), Ga(III), Fe(III), and In(III) complexes (MHDFB(+)) by host-guest complex formation. Host-guest formation constants for these supramolecular assemblies in chloroform at 25 degrees C were determined as follows : log K-a(H4DFB+) = 4.56, log K-a(AlHDFB+) = 3.48, log K-a(GaHDFB+) = 3.59, log K-a-(FeHDFB+) = 3.67, log K-a(InHDFB+) = 3.92. Chloroform extraction equilibrium constants (K-ex) for the extraction of the MHDFB(+) complexes and H4DFB+ in the presence of picrate anion by crown ether were determined as well as distribution constants (K-d) between a chloroform and aqueous phase in the absence of crown ether : log K-ex(H4DFB+) = 2.89, log K-ex(AlHDFB+) = 2.43, log K-ex(GaHDFB+) = 2.84, log K-ex(FeHDFB+) = 3.05, log K-ex(InHDFB+) = 3.46; log K-d(H4DFB+) = -1.66, log K-d(AlHDFB+) = -1.05, log K-d(GaHDFB+) = -0.75, log K-d(FeHDFB+) = -0.62, log K-d(InHDFB+) = -0.46. In the series InHDFB+, FeHDFB+, GaHDFB+, and AlHDFB+ there is increasing hydration in the second coordination shell, as suggested by a linear relationship between log (K-a,K-ex,K-d) and 1/r(i) (r(i) = M(3+) radius) and M(H2O)63f hydration enthalpy (Delta H-hyd), which consequently increases hydrophilicity (decreases K-d) and increases steric hindrance to crown ether host-guest complex formation (decreases K-a). Correspondingly, the chloroform extraction constants (K-ex = K-d.K-a), which depend on chloroform/water distribution (K-d) and host-guest complex formation (K-a), decrease in the same sequence. We conclude that the protonated amine of the free ligand H4DFB+ and its metal complexes provides a recognition site through formation of a supramolecular assembly with a crown ether. Second coordination shell effects (hydrophilicity) provide a mechanism to discriminate between different M(III) complexes of deferriferrioxamine B. The low K-d value obtained for deferriferrioxamine B distribution between the hydrophilic and lipophilic phase is consistent with previous reports concerning the therapeutic use of this ligand to remove intracellular iron from patients with iron overload.