Isomeric DTPA-amide macrocycles of p-xylenediamine and their complexation with Gd³⁺

Three DTPA-amide cyclophanes-including conformational isomers-have been isolated by optimizing the conditions of a reaction between diethylenetriaminepentaacetic (DTPA) dianhydride and p-xylenediamine: a 2 + 2-cyclization product, abbreviated as (cy2)H₆, that integrates two phenylene groups in the macrocyclic frame and bears six pendant-CH₂CO₂H arms, and two isomeric 1 + 1-macrocyles, (cy1)H₃, carrying three arms. A crucial factor for controlling the ring size is the concentration in the reaction. For (cy2)H₆, whose binuclear Gd³⁺ complex is a potential paramagnetic protein sensor, the synthetic method has been established in 70% yield. The isomerism of (cy1)H₃ is due to the conformation of the rigid macrocyclic frame; the ¹H NMR and geometry optimization show that the conformation is of quasi-C₂ symmetry in one (cy1)H₃ isomer, and of quasi-mirror symmetry in the other. Their distinct conformations define the chemical properties and coordination capability toward Gd³⁺: in the C₂-symmetric isomer, the amino nitrogen is less basic and the N-H bond is more covalent than in the mirror-symmetric isomer; the former forms a mononuclear Gd³⁺ complex whereas the latter does not show sign of complexation with Gd³⁺.