1.4.7.10- Tetraazacyclododecane-tetraacetate

After our report, many other examples of SIMs based on mononuclear lanthanide complexes have appeared. As relevant examples, we should mention the erbium-organometallic double-decker complexes [11] and the dysprosium-acetylacetonate complexes [12], and the dysprosium-DOTA (H4DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexes reported by Sessoli etal. [13]. 

Renn, O., and Meares, C.F. (1992) Large scale synthesis of the bifunctional chelating agent 2-p-nitroben-zyl-l,4,7,10-tetraazacyclododecane-N,N, N"N" -tetraacetic acid and the determination of its enantiomeric purity by chiral chromatography. Bioconjugate Chem. 3, 563-569. 

In another case, PAs were designed to function as magnetic resonance imaging (MRI) contrast agents (Bull et al. 2005) by covalently linking the peptide portion to a derivative of l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid followed by chelation of Gd ions by this moiety. The PAs were modified such that self-assembly produce either nanofibers or spherical micelles. The application of this self-assembling system could be extended to noninvasive MRI of PA scaffolds in vivo. 

A greater stability is observed for [Ln2(L13)3] (see Fig. 10) (56) these complexes are stable in water in the pH range 4-13, with a stability similar to [Ln(DOTA)]- (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The europium complex exhibits a quantum yield of only 0.0137, but has an extremely long lifetime (2.53 ms) in... 

Radionuclide chelators, such as DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or HYNIC (6-hydrazinopyridine-3-carboxylic acid), can be conjugated to Cys-tag and then loaded with radionuclides at the point of use (2,6). Furthermore, chelators can be conjugated via a PEGylated linker, which might improve the tracer s biodistribution (6). Interestingly, Cys-tag apparently has self-chelating activity that was described recently for a... 

Tetraazacyclododecane-Ar,Ar,Ar",27" -tetraacetic acid Diethylenetriaminepentaacetic acid " In-DTPA-D-Phe -octreotide... 

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. 

Since publication of CHEC-II(1996), the field covered by this chapter has expanded enormously. The development is driven mainly by an extensive use of the cycles in metal and/or anion complexation, in modeling of enzyme reactions, in catalysis, and, mostly, in medicine as contrast agents (CAs) for magnetic resonance imaging (MRI), radiopharmaceuticals, or drugs. The chemistry is mainly focused on derivatives of two of the most important macrorings 1,4,7,10-tetraazacyclododecane (cyclen) 1 and 1,4,8,11-tetraazacyclotetradecane (cyclam) 2. From related compounds, tetrakis(acetic acid) derivatives DOTA 3 (DOTA= 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TETA 4 (TETA = 1,4,8,1 l-tetraazacyclotetradecane-l,4,8,ll-tetraacetic acid) and their analogs/derivatives are of the main interest. 

The macrocycle l,4,7,10-tetraazacyclododecane-N,N, N",N" -tetraacetic acid (DOTA) is known to form stable complexes with lanthanides. A steroid conjugate (Fig. 8.16) was prepared via coupling of 6a-amino-17p-estradiol with a C functionalized DOTA derivative, namely, p-thiocyanatobenzyl DOTA, as a BFCA. The synthesis of 6a-amino-17p-estradiol was carried out by a four step reaction sequence. The intermediate and target compounds were characterized using high resolution H-NMR spectroscopy. 

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