Metal complexes with macrocyclic ligands. Part XXXVI. Thermodynamic and kinetic studies of bivalent and trivalent metal ions with 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid

Abstract

NMR, potentiometric, and UVjVIS measurements were run to study the protonation and the In3+ and Cu2+ stability constants of 1,4,7,1O-tetraazacyclododecane-1,4,7-triacetic acid (do3a, L). The protonation of do3a follows the typical scheme with two high and several low log KH values. Between pH 11 and 13, the protonation mainly occurs at the N-atom, which is not substituted by an acetate side chain. The In3+ complex is not appreciably protonated even at low pH values (pH -1.7), whereas [CuL] can add up to three protons in acidic solution to give the species [CuLH], [CuLH2], and [CuLH,], the stability of which was determined. The formation rates of the Y3+, Gd3+, Ga3+, and In3+ complexes with do3a were measured using a pH-stat technique, whereas that of Cu2+, being faster, was followed on a stopped-flow spectrophotometer. In all cases, the reaction scheme implies the rapid formation of partially protonated intermediates, which rearrange themselves to the final product in the rate-determining process. Introduction. -The field of macrocyclic complexes has gone through a rapid expansion in different directions. One of these has been the functionalization, achieved by the introduction of side chains carrying a donor group, which can act as an additional ligand for the metal ion. These compounds show interesting properties with respect to their complexation ability, selectivity, coordination geometry, and have potential applications [2]. Some of them are among the strongest chelators known, thus making them useful for medical applications, for which kinetical inertness and thermodynamical stability are of paramount importance. So, applications of macrocyclic metal complexes as contrast agents in magnetic resonance imaging (MRI) [3] and for labelling monoclonal antibodies have been described [4].The Gd3+ complexes of dota ( = 1,4,7,10-tetraazdcyclododecane-1,4,7,10-tetraacetic acid) and of dtpa (diethylenetriaminepentaacetic acid) are two of the MRI contrast agents already in use [5]. To obtain new, stable, and nonionic Gd"' chelates, Tweed2 and

Stability and Toxicity of Contrast Agents

“…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 k 1 values of the complexes of DO3A, containing only three acetates, are 2-3 orders of magnitude higher than those of the DOTA complexes presumably because protonation of DO3A occurs more easily on the secondary nitrogen than on the tertiary nitrogens [125,236]. An alcoholic OH group is weaker donor than the oxygen of a carboxylate group so dissociation of HP-DO3A and BT-DO3A complexes is expected to be faster than dissociation of DOTA complexes.…”

“…The diprotonated intermediate exists in equilibrium and can dissociate to Ln 3+ plus H 2 DOTA 2− or can re-form Ln(DOTA) − as discussed earlier in Section 4.5.1. Since complexes of DOTA and its derivatives are thermodynamically unstable in highly acidic solutions, the kinetics of dissociation can only be studied in the H + concentration range of 0.05-1.0 M by spectrophotometry, fluorescence spectroscopy, and relaxometry or by separating the Ln 3+ ion from the complex by ion-exchange or HPLC [204,205,222,236]. The first-order rate constants (k d ) obtained under these conditions are directly proportional to [H + ] up to about 0.2-0.3 M. The rate law for this mechanism can be written as follows:…”

(S)-5-(p-Nitrobenzyl)-PCTA, a Promising Bifunctional Ligand with Advantageous Metal Ion Complexation Kinetics

“… a calculated form “saturation kinetics” from reference (32), b reference (66), c data corresponds to YL complex, d reference (10), e data corresponds to EuL complex, f calculated form “saturation kinetics” obtained in a wide concentration range, g second-order dependence on H + ion concentration with third-order rate constant (5.7±0.4)×10 −5 M −2 s −1 was also observed, h reference (47), i second-order dependence on H + ion concentration with third-order rate constant 2.0 ×10 −3 M −2 s −1 was also observed (47), j t= 37 °C reference (43), k reference (45), l data corresponds to EuL (43). …”

Study of Copper(II) Polyazamacrocyclic Complexes by Electronic Absorption Spectrophotometry and EPR Spectroscopy

“…[27] The presence of protonated species in aqueous solution (MH n L, n is typically 1 or 2), along with the more stable nonprotonated form (ML), has been detected for some Cu II macrocyclic chelates. [25,28,29] Although the formation of binuclear complexes (M 2 L) has been observed in some cases in the solid state, [23] it appears to be negligible in solution. [20][21][22] Most of the Cu II tri-and tetraazamacrocyclic complexes present in aqueous solution are thus mononuclear and fiveor six-coordinate, with the metal ion probably bound to all the nitrogen atoms of the macrocyclic ring and to two or three carboxylate oxygens of its pendant arms.…”