Complexation Properties of N,N′,N″,N′′′-[1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetrayltetrakis(1-oxoethane-2,1-diyl)]tetrakis[glycine] (H4dotagl). Equilibrium, Kinetic, and Relaxation Behavior of the Lanthanide(III) Complexes

✍ Scribed by Zsolt Baranyai; Ernő Brücher; Tímea Iványi; Róbert Király; István Lázár; László Zékány

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: German
• Weight: 167 KB
• Volume: 88
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200590042

✦ Synopsis

Abstract

Eu^3+^, Dy^3+^, and Yb^3+^ complexes of the dota‐derived tetramide N,N′,N″,N′′′‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H~4~dotagl) are potential CEST contrast agents in MRI. In the [Ln(dotagl)] complexes, the Ln^3+^ ion is in the cage formed by the four ring N‐atoms and the amide O‐atom donor atoms, and a H~2~O molecule occupies the ninth coordination site. The stability constants of the [Ln(dotagl)] complexes are ca. 10 orders of magnitude lower than those of the [Ln(dota)] analogues (H~4~dota=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The free carboxylate groups in [Ln(dotagl)] are protonated in the pH range 1–5, resulting in mono‐, di‐, tri‐, and tetraprotonated species. Complexes with divalent metals (Mg^2+^, Ca^2+^, and Cu^2+^) are also of relatively low stability. At pH>8, Cu^2+^ forms a hydroxo complex; however, the amide H‐atom(s) does not dissociate due to the absence of anchor N‐atom(s), which is the result of the rigid structure of the ring. The relaxivities of [Gd(dotagl)] decrease from 10 to 25°, then increase between 30–50°. This unusual trend is interpreted with the low H~2~O‐exchange rate. The [Ln(dotagl)] complexes form slowly, via the equilibrium formation of a monoprotonated intermediate, which deprotonates and rearranges to the product in a slow, OH^−^‐catalyzed reaction. The formation rates are lower than those for the corresponding Ln(dota) complexes. The dissociation rate of [Eu(dotagl)] is directly proportional to [H^+^] (0.1–1.0M HClO~4~); the proton‐assisted dissociation rate is lower for [Eu(H~4~dotagl)] (k~1~=8.1⋅10^−6^ M^−1^ s^−1^) than for [Eu(dota)] (k~1~=1.4⋅10^−5^ M^−1^ s^−1^).