A KINETIC INVESTIGATION OF THE LANTHANIDE DOTA CHELATES - STABILITY AND RATES OF FORMATION AND OF DISSOCIATION OF A MACROCYCLIC GADOLINIUM(III) POLYAZA POLYCARBOXYLIC MRI CONTRAST AGENT

The complexation of the gadolinium(III) ion by DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracarboxylic acid) proceeds through the formation of an intermediate complex (stability constant K* = 6.9 x 10(3) M-1) in which the metal ion is incompletely coordinated as shown by NMR spectroscopy. Dyes were used to measure the pH changes that take place during the complexation process. Between pH 4 and 6, the HDOTA3- form is the kinetically active species (k(f,HL) = 1.0 x 10(6) M-1 s-1) despite its low concentration. The dissociation of GdDOTA- was investigated by scavenging the liberated Gd-153(3+) with an ion exchanger. The dissociation is exceedingly slow even in acidic solutions. It is catalyzed by the H+ ions (k(d,H) = 8.4 x 10(-6) M-1 s-1), and the acid-independent dissociation process can be neglected (k(d,0) < 5 x 10(-8) s-1). The stability constant of GdDOTA- was computed from the rates of formation and of dissociation (log K(ML) = 22.1). Contrary to earlier findings, this complex does not appear to be unusually stable. However, GdDOTA- should be a particularly safe MRI contrast agent because of its remarkable kinetic inertness.