Equilibrium and Formation/Dissociation Kinetics of Some Ln^IIIPCTA Complexes

Abstract

The protonation constants (K i H ) of 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA) and stability constants of complexes formed between this pyridine containing macrocycle and several different metal ions have been determined in 1.0 M KCl, 25°C and compared to previous literature values. The first protonation constant was found to be 0.5-0.6 log units higher than the value reported previously and a total five protonation steps were detected (log K i H = 11.36, 7.35, 3.83, 2.12 and 1.29). The stability constants of complexes formed between PCTA and Mg 2+ , Ca 2+ , Cu 2+ and Zn 2+ were also somewhat higher than those previously reported but this difference could be largely attributed to the higher first protonation constant of the ligand. Stability constants of complexes formed between PCTA and the Ln 3+ series of ions and Y 3+ were determined by using an "out-of-cell" potentiometric method. These values ranged from log K = 18.15 for Ce(PCTA) to log K = 20.63 for Yb(PCTA), increasing along the lanthanide series in proportion to decreasing Ln 3+ cation size. The rates of complex formation for Ce(PCTA), Eu(PCTA), Y(PCTA) and Yb(PCTA) were followed by conventional UV-VIS spectroscopy in the pH range pH=3.5 -4.4. First order rate constants (saturation kinetics) obtained for different ligand / metal ion ratios were consistent with rapid formation of a diprotonated intermediate, Ln(H 2 PCTA) 2+ . The stabilities of the intermediates as determined from the kinetic data were 2.81, 3.12, 2.97 and 2.69 log K units for Ce(H 2 PCTA), Eu(H 2 PCTA), Y(H 2 PCTA) and Yb(H 2 PCTA), respectively. Rearrangement of these intermediates to the fully chelated complexes was the rate determining step and the rate constant (k r ) for this process was found to be inversely proportional to the proton concentration. The formation rates (k OH ) increased with a decrease in lanthanide ion size (9.68×10 7 M -1 s -1 , 1.74×10 8 M -1 s -1 , 1.13×10 8 M -1 s -1 and 1.11×10 9 M -1 s -1 for Ce(PCTA), Eu(PCTA), Y(PCTA) and Yb(PCTA), respectively). These data indicate that the Ln(PCTA) complexes exhibit the fastest formation rates among all lanthanide macrocyclic ligand complexes studied to date. The acid catalyzed dissociation rates (k 1 ) varied with cation from 9.61×10 -4 M -1 s -1 , 5.08×10 -4 M -1 s -1 , 1.07×10 -3 M -1 s -1 and 2.80×10 -4 M -1 s -1 for Ce(PCTA), Eu(PCTA), Y(PCTA) and Yb(PCTA), respectively.

Stability and Toxicity of Contrast Agents

“…Interestingly, although the mechanism of complex formation for PCTA and DOTA complexes is similar, PCTA forms complexes with the trivalent lanthanide ions about 10 times faster than the corresponding Ln(DOTA) − complexes. Rapid formation kinetics can in this case be explained by the presence of the pyridine ring in PCTA which pre-organizes the coordination cage even more than it is in DOTA [129]. The kinetics of complex formation with functionalized DOTAtetraamide and PCTA-trisamide ligands is also very similar to those of the corresponding DOTA and PCTA complexes.…”

“…Metal ion exchange between a complex and Eu 3+ was followed by spectrophotometry at 0.1 M Gd(HP-DO3A) or Gd(BT-DO3A) and 0.01 M Eu 3+ concentration. The first-order rate constants were found to be independent of the [93,129,224,236].…”

“…The kinetic properties of PCTA are more promising; it forms complexes with the Ln 3+ ions significantly faster than does DOTA while retaining a comparable kinetic inertness. Backbone substitution of PCTA does not seem to alter the kinetic behavior of the ligand drastically based on the observation that metal ion complex formation with NO 2 -Bn-PCTA is only slightly slower than with PCTA [98,129].…”

Synthesis, characterization, and relaxation studies of Gd‐DO3A conjugate of chlorambucil as a potential theranostic agent

“…The stability constant of Gd(III)-DO3A-TR-CHL was obtained almost in the same range as that of Gd(III)-DO3A [21] and the data indicated sufficiently high thermodynamic stability of the Gd(III) complex of DO3A-TR-CHL ligand to be used as a safe MRI CA for biomedical applications. …”

Heterometallic Complexes Containing Lanthanides

“…Fig. 9.2 shows the variation in observed 23 Na chemical shift between [13] a No study of pH dependent and independent rates of lanthanide exchange has been reported for DTPA or DTPA-BMA. The values for k 1 are estimates, based on the assumption that the pH dependent pathway will dominate at pH = 1.0.…”