The 12-membered cyclic tetramine cyclen (1,4,7,10-tetraazacyclododecane) is a tetraaza macrocycle of great practical importance. Complexes of some of cyclen based ligands have found applications as MRI contrast agents, radiopharmaceuticals, luminescent probes, in vivo temperature probes, and in vivo NMR shift reagents.
The donor atoms in macrocyclic ligands are normally positioned so that they can form five or six membered chelate rings. The most common macrocycles have four donor atoms, usually nitrogens and between 12 and 17 members. The 12-membered cyclic tetramine cyclen (1,4,7,10-tetraazacyclododecane) is a tetraaza macrocycle of great practical importance. The unsubstituted secondary tetraamine itself is too small to completely encircle a metal ion so cyclen will coordinate in a way that the metal ion lies out of the plane of the four nitrogen donor atoms. Cyclen derivatives with pendant arms, however, can coordinate a large variety of metal ions in an axial fashion, so that the central metal ion is positioned between the planes of the four nitrogens and the planes of the donor atoms (usually oxygen) of the pendant arms (in basket). Complexes of some of cyclen based ligands have found applications as MRI contrast agents, radiopharmaceuticals, luminescent probes, in vivo temperature probes, and in vivo NMR shift reagents. The 14-membered tetraaza macrocyle cyclam (1,4,8,11-tetraazacyclotetradecane) is large enough to encircle many metal ions. Trans planar coordination of the nitrogen atoms occur in complexes with nickel(II), nickel(III), cobalt(II), cobalt(III), copper(V) and technetium(V). Due to the inherent flexibility of the cyclam ring it can coordinate to metal ions of different size. Other importat tetraaza macrocycles include the natural porphyrines and the structurally closely related synthetic phthalocyanines. Saturated cyclic polyamines such as triazacyclononane, cyclen and cyclam are synthesized by macrocyclization reactions such as the Richman Atkins procedure. These cyclization reactions involve ring formation by twoprecursor fragments of the cyclic molecule. Usually one fragment consist of a asalt of a sulfonamideand the other contains two terminal leaving groupssuch as bromide or tosylate. The cyclization reaction is run in a polar aprotic solvent such as DMF or acetonitrile and may involve high dilution conditions. Metal ion template mediated cyclizations have also been reported.