title: Kinetics of the exchange reactions between Gd(DTPA)2-, Gd(BOPTA)2-, and Gd(DTPA-BMA) complexes, used as MRI contrast agents, and the triethylenetetraamine-hexaacetate ligand.
abstract: The kinetics of ligand exchange reactions occurring between the Gd(DTPA), Gd(BOPTA), and Gd(DTPA-BMA) complexes, used as contrast agents in MRI, and the ligand TTHA, have been studied in the pH range 6.5-11.0 by measuring the water proton relaxation rates at 25 °C in 0.15 M NaCl. The rates of the reactions are directly proportional to the concentration of TTHA, indicating that the reactions take place with the direct attack of the H(i)TTHA((6-i)-) (i = 0, 1, 2 and 3) species on the Gd(3+) complexes, through the formation of ternary intermediates. The rates of the exchange reactions of the neutral Gd(DTPA-BMA) increase when the pH is increased from 6.5 to 9, because the less protonated H(i)TTHA((6-i)-) species can more efficiently attack the Gd(3+) complex. The rates of the exchange reactions of [Gd(DTPA)](2-) and [Gd(BOPTA)](2-) also increase from pH 8.5 to 11, but from 6.5 to 8.5 an unexpected decrease was observed in the reaction rates. The decrease has been interpreted by assuming the validity of general acid catalysis. The protons from the H(i)TTHA((6-i)-) species (i = 2 and 3) can be transferred to the coordinated DTPA or BOPTA in the ternary intermediates when the dissociation of the Gd(3+) complexes occurs faster. The kinetic inertness of Gd(DTPA), Gd(BOPTA), and Gd(DTPA-BMA) differs very considerably; the rates of the ligand exchange reactions of Gd(DTPA-BMA), thus the rates of its dissociation, are 2 to 3 orders of magnitude higher than those of Gd(DTPA) and Gd(BOPTA). The rates of the ligand exchange reactions increase with increasing concentration of the endogenous citrate, phosphate, or carbonate ions at a pH of 7.4, but the effect of citrate and phosphate is negligible at their physiological concentrations. The increase in the reaction rates at the physiological concentration of the carbonate ion is significant (20-60%), and the effect is the largest for the Gd(DTPA-BMA) complex.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen H-4010, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Pálinkás
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Baranyai
authors.forename: Erno
authors.initials: E
authors.lastname: Brücher
authors.forename: Béla
authors.initials: B
authors.lastname: Rózsa
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D019786:Gadolinium DTPA / Q000031:analogs & derivatives / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008536:Meglumine / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D008024:Ligands; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; C026059:triethylenetetraminehexaacetic acid; D004492:Edetic Acid; D019786:Gadolinium DTPA