The synthesis of 18-membered macrocyclic ligands containing saturated amine and either pyridine or furan heterocyclic units is described. The protonation equilibria were studied by potentiometric titrations in which four protonation steps were observed for each ligand in the pH ranges 3-12. The protonation mechanism of these macrocyclic ligands was determined from potentiometric titrations followed by NMR and is consistent with protonation of only the saturated amine groups in the pH range studied. The formation constants for complexes of pyo2[18]dieneN6 with Ca(II), Mg(II), Mn(II), Cu(II), Zn(II), Cd(II), La(III), and Gd(III), determined potentiometrically, follow the order of the Irving-Williams series and are consistent with 1:1 metal ion binding. Furthermore, py02[18]dieneN6 binds as well or better than its saturated homolog, [ 18]aneN6. In contrast, furo2[l 8]aneN402 doesnot bind effectively in comparison to the saturated homolog, trans-[ 18]aneN402. The difference in binding may be due to a combination of enthalpic (polarity of ligating groups and steric strain of the ligand) and entropic (rigidity of the ligand) contributions.