Co-ordination chemistry and molecular mechanics study of the magnesium(II) and calcium(II) complexes of trisubstituted 1,4,7-triazacyclononane derivatives

The affinities of 1,4,7-tris(2-hydroxyalkyl)-1,4,7-triazacyclononane derivatives for Mg^II and Ca^II were found to differ greatly. Whereas 1,4,7-tris(2-hydroxyethyl)- (L¹), 1,4,7-tris(2-hydroxy-2-methylpropyl)- (L²) and the unsymmetrical 1,4,7-tris(2-hydroxypropyl)-1,4,7-triazacyclononane derivative L^3b barely discriminated between Mg^II and Ca^II, the symmetrical isomer L^3a was more than 500 times more selective for Mg^II than for Ca^II. Similar selectivity differences were observed between the diastereomers of 1,4,7-tris(2-hydroxy-2-phenylethyl)- (L⁴) and 1,4,7-tris(2-hydroxydodecyl)-1,4,7-triazacyclononane (L⁵). These selectivities were related to the structure of the magnesium complexes as shown by molecular mechanics (MMX) calculations. Only those ligands favoring the formation of a magnesium complex with a large twist angle between the planes of co-ordinating oxygens and ring nitrogens resulting in a small, tight cavity showed a large preference for Mg^II over Ca^II. The MMX calculations predicted large twist angle structures for phosphinate derivatives, and for a phosphonate monoester derivative, and these ligands were found to have a high selectivity for Mg^II. Similarly, the calculated preference for the smaller twist angle correctly predicted the lack of Mg^II/Ca^II selectivity for acetate and amide derivatives and for a phosphonate diester derivative. Equilibration of the complexes of the ligands in the presence of both Mg^II and Ca^II was slow, as shown for example by k_d,0 = 2.1 × 10^-4 s^-1 for CaL^3a. These dissociation rates were a factor of 100 times larger at the boundary of a two-phase (water-chloroform) system.