Macrocyclic ligands with pendent amide and alcoholic oxygen donor groups

Abstract

Bonding of the neutral oxygen donor to metal ions is discussed in relation to metal ion selectivity. Important factors are (a) inductive effects of alkyl groups attached to the oxygen donor atom, so that donor strength increases H2O < ROH < R2O, where R is an alkyl group, including ethylene or other alkyl groups forming bridges between donor atoms of multidentate ligands, and (b) size of the chelate ring formed, such that large metal ions achieve minimum strain energy when coordinated as part of five-membered chelate rings, while six-membered chelate rings favor small metal ions. Metal ions coordinate to alcohols or ethers lying in the same plane as the oxygen donor atom, and the two carbon or hydrogen atoms attached to the oxygen donor atom. This is discussed in terms of how the planarity of coordination about the oxygen donor atom alters selectivity patterns relative to neutral nitrogen donor atoms, where the geometry around the nitrogen coordinated to a metal ion is approximately tetrahedral. Addition of neutral oxygen donors as pendent alcoholic (2-hydroxyethyl and 2-hydroxypropyl) groups, or as amide (acetamide) groups, leads to changes in selectivity for metal ions that are as expected from arguments in terms of chelate ring size, and the donor strength of the alcoholic or amide oxygen. Thus, ligands based on cyclen (1,4,7,10-tetraazacyclododecane) with alcoholic and amide oxygen donor groups show large shifts in selectivity in favor of large metal ions such as Ca(II), Cd(II), or Pb(II). The potential of such ligands in treating Cd or Pb toxicity is discussed. The effect of addition of C-alkyl groups to the ethylene bridges of oxygen donor ligands is shown to produce shifts in selectivity in favor of small metal ions. This effect is particularly marked in novel ligands that contain cyclohexenyl bridges in place of ethylene bridges between the donor atoms. Such ligands are of potential interest in biomedical applications.