Cyclen derivatives

N3-coordination by monomeric and dimeric Zn2+-cyclen derivatives has also been shown to both inhibit the photo [2+2] cycloaddition of thymidilyl(3 -5 )thymidine, d(TpT), and to accelerate the photosplitting process of the [T-cis,syn-T] dimer (78% after 1 h of UV exposure) (38). 

Fig. 7. A Zn21 -cyclen derivative (3) with coordinated captopril, and molecular structure of a Znn(cyclen)-N3 bound 1-MeT.

Fig. 8. Schematic for the micrococcal nuclease attack to (a) breathing ds-DNA, (b) dista-mycin-bound DNA, and (c) Zn2+-cyclen derivative-bound DNA. Arrows and dashed arrows, respectively, indicate successful and failed enzyme hydrolysis. Reproduced with permission from Ref. (37). Copyright 1999, American Chemical Society.

These corrections, whilst applicable to a variety of systems, were determined for use with cyclen derivatives. A more wide ranging correction for q values of europium complexes has been postulated by Supkowski and Horrocks (25), using data for 25 complexes taken from the literature. Their new equation is ... 

Zucchi, G. Scopelliti, R. Biinzli, J.-C. G. Importance of the chromophore orientation to the ligand-to-metal energy transfer in lanthanide complexes with pendant-arm fitted cyclen derivatives. J. Chem. Soc., Dalton Trans. 2001, (13), 1975-1985. 

Thus, in analogy to the above outlined procedure cyclen is converted to 12 and without isolation reacted with 4,4-dimethyl-3,5,8-trioxabicyclo [5.1.0] octane to give the formyl derivative 13 which also without isolation is treated with aqueous hydrochoric acid under heat. Under these conditions both the formyl group is removed and the dioxepanyl ring gives rise to the free butrol side chain yielding the monosubstituted cyclen derivative in the form of its tetrahydrochloride 16. The overall yield for this reaction sequence is about 81%... 

Comparison between actual (q) and calculated (gCorr) hydration states for Yb111 complexes with cyclen derivatives... 

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. 

Fig. 4.12. Illustration of the induced fit principle in the case of a cyclen derivative, DOTA (top), of podands (middle) and of self-assembly processes (bottom).

Recently, it has been proposed that the Eu(II) cryptate with (2.2.2) is a good contrast agent for magnetic resonance imaging (see section on cyclen derivatives below). Firstly, the electronic configuration of the ion is identical to the one of Gd(III) secondly, two water molecules can interact with the Eu(II) ion, which is ten coordinate in water, instead of... 

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,... 

Guanidinium salt 139 was synthesized from the reaction of dry cyclen 1 hydrochloride with tetraethyl orthocarbonate (EtOH, reflux, 19 h, 96%) and transformed into various cyclen derivatives (Scheme 20) <1998ACS1247>. 

Table 1 Monosubstituted cyclen derivatives according to Scheme 23...

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. 

Incorporation of (111) into a kinetically stable complex suitable for attachment to an antibody calls for an octadentate ligand, and so pendant-arm cyclen derivatives are appropriate. In particular, two or three antigen-binding fragments of an antibody (Fabs) have been attached to the di- or trimaleimide ligands 80-82 (Scheme 8) (90, 91)... 

---