Tetraazacyclododecane-tetraacetic acid

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... 

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. 

A second compound that has been used is Ytterbium tetramethyl-1,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid (DOTMA) with octa-coordinate bonding of the ligand to Yb via four nitrogen and four oxygen atoms. The twelve equivalent protons of the methyl groups have a resonance at -18 ppm relative to water, and show a temperature dependence of -0.04 0.01 ppmK. The chemical shift difference between the ac and axl proton resonances in the ligand was measured in human serum and found to be linear over a range of 308-318 K with a sensitivity of -0.41 ppmK. ... 

Yao Z, Zhang M, Garmestani K, Axworthy DB, Mallett RW, Fritzberg AR, et al. Pretargeted a emitting radioimmunotherapy using Bi 1,4,7,10-tetraazacyclododecane-N,N, N",N"-tetraacetic acid-biotin. Clin Cancer Res 2004 10 3137-3146. 

Conjugation of l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid (DOTA) and its derivatives to peptides, applications and future prospects of the conjugates 07MRO281. 

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