1,4,7,10-Tetraazacyclododecane derivatives

Tetraaryltin compounds, 24 810-811 Tetraazacyclododecane derivatives, 24 56 Tetraazaindoles, as chemical stabilizers, 19 365... 

I, 4,7,10-Tetraazacyclododecane Derivatives Obtained Therefrom and N-Arylethyl-ethanolamine Sulfonate Esters as Intermediates... 

Nwe K, Richard JP, Morrow JR. Direct excitation luminescence spectroscopy of Eu(III) complexes of l,4,7-tris(carbamoylmethyl)-l,4,7,10- tetraazacyclododecane derivatives and kinetic studies of their catalytic cleavage of an RNA analog. Dalton Transactions. 2007 2007 (44) 5171-5178. 

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 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. 

In principle, lanthanide complexes of alkyl- (phosphinates) or alkoxy- (phosphonate esters) DOTP derivatives may give rise to 32 stereoisomers, existing as 16 enantiomeric pairs, which are indistinguishable by NMR spectroscopy. The isomers originate from chiral elements inherent in these complexes, including the R or S configuration at each phosphorus and the helicity defined by the pendant arm orientations (AIA). Various Ln3+ complexes of phosphinate and phosphonate ester ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) have been described in the literature [104-107]. 

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. 

In addition to triprotected cycles (Section 14.11.6.1), some trisubstituted cycles are very important. In particular, D03A 183 (D03A= l,4,7,10-tetraazacyclododecane-l,4,7-triacetic acid) or its esters are intermediates for a number of unsymmetrically substituted cyclen derivatives (see below). The most important ester is tris(Bu ) ester 184. 

HSA binding not only interferes with the inner-sphere water molecules, but also the outer-sphere. DOTP( 1,4,7,10-tetraazacyclododecane-N, N , N , A "-tetrakis(methylenephosphonic acid) derivatives have no inner-sphere water molecule, and rely on the outer-sphere mechanism. This property allows the study of how HSA binding sites affect relaxivity, which shows that differences in r are solely due to the nature of the binding sites [77,78]. 

One-stage synthesis of medium-sized unsaturated lactones, thiolactones, and lactams of fi-configuration using the Bellu-Claisen rearrangement 04AG(E)3516. Syntheses of 1,4,7,10-tetraazacyclododecane and its derivatives 03MI91. 

Intramolecular photocycloaddition occurs with thymine derivatives and related compounds. Thus, the bis thymine dimer (116) is formed on irradiation at 254 nm of (117). Zinc complexes of 1,4,7,10-tetraazacyclododecane inhibit the intramolecular photodimerisation of the thymidilyl thymidine (118) and the same complexes are active in cleaving cyclobutane systems (119). Conventional (2+2)-cycloaddition does not occur on irradiation of (120) but instead the main product is the cytosine hydrate accompanied by the (6-4)-photoproduct (121). Dimerisation is reported to occur on irradiation in an acidic medium. 

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