Gd-DOTA derivatives

Numerous Gd—DOTA derivatives show pH responsiveness. This phenomenon derives from mobile protons of coordinated water molecules or chelates. The exchange can be an acid- or base-catalyzed prototropic exchange, and is expressed as follows (Equation 10.13). 

The formation of micellar structures has also been observed for a calix[4]arene decorated with Gd-DOTA derivatives on the upper rim (propyl groups have been introduced on the lower, narrow rim to lock the calix[4]arene in the cone conformation (Scheme 3)). These systems form very small spherical nvicelles with a radius of 2-8 nm in water. The calix[4]arene platform bearing the four Gd-complexes already brings a considerable relaxivity increase with respect to the monomer chelates (ri = 17.1 s mM ... 

Recently, a tumor-targeting self-assembled chitosan polymer was reported by Nam et al. for optical-MR dual modality imaging. Cy5.5 NIR fluorescent dyes and Gd-DOTA derivatives were covalently attached to an... 

A sizeable contribution of the term rf has also been evidenced in the study of the pH-dependence of the relaxivity in the case of the Gd(III) complexes with tetraamide DOTA derivatives. As previously discussed, these cationic monoaqua complexes are characterized by a slow rate of exchange of the coordinated water molecule, which strongly limits the inner sphere... 

A second class of MRI contrast agents contains ligands that are derivatives of the macrocydic tetramine, 1.4.7.10-tetraazacyclododecane (cyclen). Gadoterate (Dotarem, Gd-DOTA, Scheme 3, formula 5) was the first macrocydic gadolinium complex which has entered the market. 

The success of [Gd(DOTA)] as a CA has initiated an intensive search for derivatives with improved properties, such as complexes of D03A derivatives. The nonionic reagents Gd(HP-D03A) and Gd(D03A-butrol), in which one of the acetate groups of DOTA is replaced by a hydroxyalkyl group, have recently been introduced. 

Linear copolymers of Gd(DTPA-bisamide) or Gd(EGTA-bisamide) units with poly(ethylene-glycol) (PEG) or polyalkyl (-(CH2)n- n = 6,10 and 12) spacers also had water exchange kinetics similar to that of the corresponding monomer chelate [60-62]. An 170 NMR study on the micellar system formed in aqueous solution of the amphiphilic DOTA-derivative [Gd(D0TA-C12)(H20)] also showed that the water exchange is not altered by the micellar structure [63]. 

The most thermodynamically stable and kinetically inert complexes of the trivalent lanthanides are those of the ligand DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) (42, 43). Our search for lanthanide macrocyclic complexes that would remain intact for longer time periods led us to examine derivatives of DOTA. There are two potential difficulties with the use of DOTA complexes of the trivalent lanthanides for RNA cleavage. First, the overall negative charge on the complex is not conducive to anion binding for example, Gd(DOTA)-does not bind hydroxide well (44). Second, DOTA complexes of the middle lanthanides Eu(III) and Gd(III) have only one available coordination site for catalysis. The previous lanthanide complexes that we used, e.g., Eu(L1)3+, were good catalysts and had at least two available coordination sites. 

Kinetic Stabilities of Gd + Complexes of DOTA and DOTA Derivative... 

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