120066-54-8Relevant articles and documents
Preparation method and application for gadolinium ion type contrast agent intermediate
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Paragraph 0079; 0081; 0085, (2019/05/15)
The invention provides a preparation method and an application for a gadolinium ion type contrast agent intermediate. The preparation method comprises the following steps: allowing a substance as shown in a general formula (II) which is described in the specification to react with a substance as shown in a general formula (III) which is described in the specification or a substance as shown in a general formula (IV) which is described in the specification in the presence of an alkaline catalyst so as to generate the gadolinium ion type contrast agent intermediate with a structure as shown in ageneral formula (I) or a general formula (V) which are described in the specification. In the general formulas as described in the specification, R represents a group selected from the group consisting of C1-C5 alkyl groups, benzyl groups and benzyl derivatives; R1 represents -H or -CH2OH; and R2 represents -CH3 or -OH. The above-mentioned preparation method used to prepare the gadolinium ion type contrast agent intermediate with a structure as shown in the general formula (I) which is described in the specification has the advantages of simple reaction, fewer steps and controllable reaction,and can reach a yield of 99% or above; and a product obtained by using the preparation method provided by the invention has a purity of more than 99.5%.
Ligand basicity and rigidity control formation of macrocyclic polyamino carboxylate complexes of gadolinium(III)
Kumar, Krishan,Tweedle
, p. 4193 - 4199 (2008/10/08)
The formation reaction rates of some macrocyclic polyamino carboxylate complexes of gadolinium, GdL (where L is DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, H3L, HP-DO3A = 10-(hydroxypropyl)-1,4,7,-10-tetraazacyclododecane-1,4,7-triacetic acid, H3L, and DO3MA = (1R,4R,7R)-α,α′,α″-trimethyl-1,4,7,10- tetraazacyclododecane-1,4,7,10-triacetic acid, H3L), have been measured at 25.0 ± 0.1°C and at a constant ionic strength of 1.0 (NaCl) by an indicator method. The formation reactions are first order in the limiting reagent (ligand) and nearly independent of the excess reagent (gadolinium ion). A mechanism of the formation of the gadolinium complexes involves the formation of a precursor (intermediate) complex, Gd(*HL), in an equilibrium step followed by its deprotonation and reorganization to the final product in the rate-determining step. The stability constants (log KGd(*HL)) of the intermediate have been determined from the kinetic data and the values are 8.9 (DO3A), 9.0 (HP-DO3A), and 10.7 (DO3MA). The nature of the intermediate is proposed in which the metal is coordinated to oxygens and at least one nitrogen of the ligand. Deprotonation and reorganization of the intermediate are specific-base assisted. The second-order rate constants (kOH, M-1 s-1) for the reorganization of the intermediate, Gd(*HL) (L are given in the parentheses), are (2.1 ± 0.1) × 107 (DO3A), (1.23 ± 0.04) × 107 (HP-DO3A), and (7.2 ± 0.3) × 104 (DO3MA), compared to the literature data (7.1 ± 1) × 107 (NOTA) and (5.9 ± 0.2) × 106 (DOTA). The specific-base assisted rate of reorganization of the intermediate, Gd(*HL), is correlated with the ligand strain energy and its first protonation constant. These observations lead us to conclude that the rate of reorganization of the intermediate is governed by the basicity and rigidity of the ligand.
