Cyclen-derivative macrocycles

It is only recently that S. Faulkner took advantage of the kinetic inertness of Lnm cy-clen macrocyclic complexes for producing the neutral pure heterotrimetallic compound [Yb(116b)] (fig. 96) in which convergent directional intramolecular Tbm - Ybm processes are responsible for the sensitization of the NIR Yb(2F5/2) emission (Faulkner and Pope, 2003). The complex is stable in water and according to the lifetime measured (1.83 and 4.22 ps in H2O and D2O, respectively), the hydration number of Yb111 is close to zero (heptadentate cyclen derivative. 

The metal template method is commonly used for the syntheses of metal complexes of ligands derived from the title macrocycles. Mostly, the central ion could not be removed to get a free cyclic ligand thus, there are limited examples of ligand syntheses by this method. C-Aryl cyclen derivatives 74 were prepared using the small Fe3+ ion as a template <1998NJC1359>. Condensation of Fe(m) complex of 2,2,2-tet with arylglyoxals formed imine complexes,... 

The photophysics of lanthanide complexes has drawn considerable attention in recent years, in part because of the potential applications of lanthanides (sensors, electroluminescent displays, etc.) and several recent reviews highlighting applications of luminescent lanthanide complexes have appeared. A discussion of infrared f-f luminescence of Yb, Nd, and Er in complexes having macrocyclic ligands such as porphyrins, cyclen derivatives, and calixarenes was published by Korovin and Rusakova. " In addition, DaSilva and co-workers describe the development of highly luminescent lanthanide complexes and their application as light-conversion molecular devices. ... 

Crystal structures of Ln complexes of DTPA and DOTA derivatives show that Ln +-bound diethylenetriamine moieties in these complexes always occur either in the 88 or in the X.X. conformation (Scheme 5.10). In these complexes, the steric interactions are always minimized. Upon coordinated by a metal ion, the central nitrogen atom is chiral. The inversion is precluded if the nitrogen is coordinated to the metal. A common feature of cyclen-based macrocyclic Gd (and other Ln ) is the formation of various isomers which display dynamic behavior (interconvert/exchange) on the NMR time scale in aqueous solution [174,175]. However, the long electronic relaxation time of Gd ion prevents the observation of the NMR spectra of its complexes and its solution structure has been inferred from the H and NMR spectra of its related Ln complexes. 

Zucchi, G. Ferrand, A.-C. Scopelliti, R. Btinzli, J.-C. G. Highly luminescent, visible-emitting lanthanide macrocyclic chelates stable in water and derived from the cyclen framework. Inorg. Chem. 2002, 41, 2459-2465. 

A range of three-ring, linked aza macrocycles incorporating 9-membered 1,4,7-triazacyclononane (tacn), 12-membered cyclen and 14-membered cyclam and its derivatives have been reported but the number is much less than for the corresponding systems incorporating two linked macrocycles systems containing four or more linked rings are quite rare. 

Therefore, another strategy was developed, based on the induced-fit concept, which uses flexible receptors in order to optimize the interactions between the donor atoms and the metal ion. In fact, the coordination environment is built upon complexation thanks to the flexibility introduced into the complexation agent, which is now termed predisposed ligand . These receptors are either large macrocycles able to wrap around the guest or small macrocycles fitted with pendant arms. The latter approach has proved to be very successful, particularly with calixarene (Asfari et al., 2001) and cyclen (1,4,7,10-tetraaza-dodecane) (Lukes et al., 2001) derivatives. 

One of the most studied class of macrocyclic ligands in lanthanide coordination chemistry is without any doubt the molecules derived from cyclen, a 12-membered ring bearing four amino functions. In particular, its tetracarboxylic derivative H4DOTA (see Fig. 4.40) was synthesized in 1976 by a German chemist, H. Stetter from the University of Aachen,... 

The structural characteristics of cyclen and cyclam and their carboxylic and amidic derivatives in variously protonated states as well as their metal complexes were excellently reviewed by Guilard and co-workers <1998CCR1313>. As those derivatives are frequently used in the complexation of transition metal or lanthanide ions, the space arrangement, exact protonation sites, and presence of intramolecular hydrogen bonds are of interest from the point of view of kinetics of complex formation/dissociation. Since the number of related structures is very high, but no new remarkable information appeared since Guilard s review, derivatives of these macrocycles are not discussed in detail. 

Another general method for the synthesis of these macrocycles is the reaction of amines with (active) esters of carboxylic acids leading to oxoderivatives of the cycles. The amides can be reduced to amines or directly used for further transformations or complexation of metal ions. Two cyclens 55 and 56, as intermediates for the synthesis of bifunctional DOTA derivatives, were obtained by condensation shown in Scheme 10 between appropriate diamine-amide and active ester of AT-BOC-iminodiacetic acid (BOC = /-butoxycarbonyl), followed by deprotection and reduction <2003NMB581>. 

Some representative disubstituted cyclen 1 derivatives are listed in Table 3 and cyclam 2 derivatives are listed in Table 4. Disubstituted derivatives where the substituents serve as protecting groups as well as some another disubstituted macrocycles were also shown in Section 14.11.6.1. 

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

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