Tetraazacyclododecane-tetraacetic acid DOTA

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. 

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. 

A chromatographic interlanthanide separation by cation exchange in the presence of 1,4,7,10-tetraazacyclododecane-N,N, N",N" -tetraacetic acid (DOTA), present as an aqueous complexant, has been reported by Merciny et al. (1986). In this system the lanthanides are separated into two groups based on the rate of decomposition of the R-DOTA complex. Separation factors are not large, but a chromatographic separation of Gd and Eu is suggested. 

Kemple et al. have included contact shifts as variable parameters in a fitting procedure of LIS values with the laboratory frame version of equation (3). Forsberg et al. have further expanded this procedure and demonstrated its usefidness by a study on the solution structure of a l,4,7,10-tetraazacyclododecane-/V, N, N", A/" -tetraacetic acid (DOTA) derivative. ... 

When complexing the ligand with the lanthanide ion, many processes occur, including desolvation/solvation processes and successive formation of intermediate species Lanthanides Coordination Chemistry). In most cases, the complex is formed within seconds, with some exceptions such as l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid (DOTA) complexes. In the latter, the reaction is very slow and the equilibrium will take several days to establish. As a consequence, at room temperature, the solution will be stirred for more than 5 days, whereas on gentle warming of the solution, the delay can be reduced to half (this is the golden rule in kinetics on increasing the reaction fl om room temperature to 10 °C more, the rate should be increased by approximately a factor of two). 

Ahrends et al. described a metal-coded affinity tag (MeCAT) for the relative and absolute quantification of peptides and proteins (Figure 4.1 Ic). A macrocyclic metal chelate complex (l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid, DOTA) loaded with different lanthanide ions as the essential part of the tag. If required, the structures of peptides can be determined using ESI or MALDI MS/MS data, but the quantitative information comes from ICP-MS measurements. Peptides tagged with the reagent loaded with different metals co-elute in liqnid chromatography. The calculated detection limit for the example of bovine sernm albumin is llOamol. They have also used MeCAT to analyze proteins of the Sus scrofa eye lens as a model system. These data... 

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]. 

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... 

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 tetraazamacrocycle DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) forms stable complexes with the trivalent lanthanides, and consequently has been used in MRI as its gadolinium complex under the trade name DOTAREM. A vast number of ligands have been developed that use the tetraazacyclododecane (cyclen) ring with a variety of pendant groups many of these have... 

VEGF, vascular endothelial growth lactor DOTA, 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid D03A, 1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic acid GD03A, Gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid EPTPA, Ethylenepropylenetriamine-N, N, N, N", N"-pentaacetic acid PDT, Photodynamic therapy. 

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