Metal Complexes with Macrocyclic Ligands. IX. Synthesis and properties of a new class of branched N4-macrocycles with an additional ligating group in the side chain

In the presence of Ni²⁺ the template reaction between 2,6-diacetylpyridine and 4-(2-dimethylaminoethyl)- or 4-(2-hydroxyethyl)-1, 7-diamino-4-azaheptane yields the complexes of either the open-chain ligand ( 3 and 11 ) or of the macrocycle ( 4 and 12 ). Reduction of the imino group in 4 and 12 with PtO₂/H₂ gives 5 and 13 , respectively. In the case of the dimethylamino derivative 5 a mixture of at least four isomers was obtained. These were partially separated by chromatography on Sephadex SP-25 cation exchanger. Through demetalation of the Ni²⁺ complexes by cyanide the new macrocycles 7 and 14 were isolated, from which the corresponding Zn²⁺ and Cu²⁺ complexes were prepared. The macrocyclic Ni²⁺-complexes 4, 12, 5 and 13 can exist in two forms depending on the pH of the solution. At low pH protonation of the dimethylamino or hydroxy group in the side chain occurs. The metal ion is then bound to the four nitrogen atoms of the macrocycle in a square planar ligand field. At higher pH, however, the dimethylamino or hydroxy group (the last one also in its deprotonated form) can coordinate to one of the axial positions, whereby pseudooctahedral coordination geometry is induced. This reaction can be quantitatively described by a reversible acid-base equilibrium, the pK_H of which greatly depends on the nature of the functional group, the degree of unsaturation of the macrocycle and the metal ion. The acid-base reaction and the concomitant structural change are a direct consequence of the unique combination of the rigid and kinetically stable structure of the macrocycle and of the flexible and kinetically labile functional group of the side chain.