Cyclam derivatives

Tabushi and Fujiyoshi have prepared alkylated cyclam derivatives for the purpose of suspending these systems from a polymer backbone. They have utilized a malonic ester alkylation reaction followed by cyclization and reduction to accomplish this end. ... 

A cyclam derivative with an amine pendent donor attached at the bridgehead carbon atom was presynthesized from diethylaminomalonate and l,9-diamino-3,7-diazanonane in refluxing MeOH, followed by BH3-THF reduction.1507 It acts as a pentadentate ligand at pH 8.5 and forms a six-coordinate complex (592) with a water molecule sitting at the remaining axial site. 

The high-spin/low-spin interconverison in a Ni11 complex of the cyclam derivative (639) bearing a luminescent naphthalene substituent has been used as a fluorescent molecular thermometer.161 The Ni11 tends to quench fluorescence of the proximate naphthalene subunit, but the two spin states exert a different influence on the emission properties. Emission is temperature dependent, since the high spin —> low spin conversion is endothermic, i.e., a temperature increase favors formation of the low-spin form. 

A Ni11 complex of a cyclam derivative with protonated amine pendant also catalyzes the electrochemical reduction of C02 to CO efficiently.1507... 

Modified electrodes containing cyclam derivatives have been prepared. The approach utilizing cyclam incorporated in Nafion film on a carbon electrode shows that the catalytic efficiency of the system is much lower than observed when the catalyst is adsorbed on the mercury. With electrodes prepared following the Langmuir Blodgett technique, only the electrode materials that allow the orientation of the monolayer so that the tail points to the substrate were found to be electrocatalytically active.165... 

Reduction of (132) yields the analogous bis-cyclam derivative which, as expected, exhibits related chemical properties to its isomer (131). 

In order to investigate further the relationship between in-plane interaction and ease of oxidation of the central metal ion, a study of the oxidation of Ni(ii) and Cu(n) complexes of the cyclam derivative (287) was investigated (Fabbrizzi, 1985). This dioxocyclam ligand (287) coordinates to a divalent metal ion with deprotonation of the amido groups. 

Formation kinetics for eight tetraaza macrocycles of the cyclam type reacting with copper(II) have been analyzed in terms of rate constants for reaction with [Cu(OH)3] and with [Cu(OH)4]2. There is a detailed discussion of mechanism and of specific steric effects (292). Complex formation from cyclam derivatives containing -NH2 groups on the ring -CH2CH2CH2- units proceeds by formation followed by kinetically-distinct isomerization. The dramatic reactivity decreases consequent on... 

HIV-1, RNase H enzyme, 46 307 HIV virus, inhibition by bis(cyclam) derivatives, 45 76... 

The configuration of the macrocyclic ligand affects the electrochemical properties of Ni(II) complexes (Table I) (56a, 54). For example, the oxidation and reduction potentials of CR,S,R,S)-[Ni(14)]2+ are shifted by +0.14and +0.13 V, respectively, compared with those of the Rfi,S,S isomer. Similar trends are also observed for a series of R,Sfi,S and Rfi,S,S isomers of -methylated cyclam derivatives (61a, 61b). The anodic shift of the redox potentials for the i ,S ,S-Ni(II) complex indicates that the complex is more difficult to oxidize to Ni(III) but easier to reduce to Ni(I), compared with the RJl,S,S complex. This may be related to the reduced ligand field strength of the R,Sfi,S complex, which stabilizes the antibonding -orbitals and thus makes addition of an electron more favorable while removal of an electron is less favorable. 

Cyclam derivatives such as 3.75 with hydroxypropyl side arms engage in a lariat ether-like coordination of one hydroxyl group to give square pyramidal complexes that hydrogen bond to anions... 

Based on published procedures for preparing both di- and tri-N-protected tert-butoxycarbonyl (Boc) cyclam derivatives [27], we developed the alternate procedure shown in Scheme 2 for obtaining the tri-branched species 11 [28] as well as related procedures for the new tri-branched derivative 12 (see Scheme 3) [28], the linearly linked derivative 13 [28] and the linked cyclic derivative 14 [29], In the case of the phloroglucinol derivative, tri-Boc protected cyclam was first acylated with chloroacetyl chloride the resulting chloromethylamide was then used to trialkylate phloroglucinol in DMF at 70 °C over caesium carbonate as outlined in Scheme 3. Subsequent... 

The interaction of the linearly linked tris-cyclam derivative 13 with Ni(II), Cu(II), Zn(II), Cd(II), and Pd(II) has been investigated [32], As for the above tri-branched systems, all five metals yield solid complexes in which the metal ligand stoichiometry is 3 1 with, for Cu(II), a spectrophotometric titration also confirming the formation of a complex of this stoichiometry in acetonitrile. Cyclic voltammograms of both the Ni(II) (low-spin) and Cu(II) complexes both yield evidence for the presence of M(II)/M(III) as well as M(I)/M(II) couples in acetonitrile. 

The ability of cyclam derivatives to bind heavy metal ions [131] has been exploited with (60) [75] which shows good fluorescence enhancements with zinc and cadmium ions at pH 10. In such polyamine receptors, it is necessary that all the nitrogen lone pairs occupy the first coordination sphere of the metal ion in order that the fluorescence is efficiently revived. The unusual spectral shape of... 

The partially protonated cyclen and cyclam and their derivatives are present in aqueous solution in some stable conformations stabilized by intramolecular hydrogen bonds. It leads, for example, to broad signals in NMR at room temperature and intermediate pH. Such hydrogen bond-stabilized structures are sometimes rather stable as it was proved, for example, in the case of l,8-bis(methylphosphonic acid) cyclam derivatives where solution structure is probably the same as found in the solid state <2000CCC1289>. These closed structures are opened after full protonation. 

Analogous cw-glyoxal aminal 129 derived from cyclam 2 was prepared similarly < 1996CC947>, and it was used for the same kind of protection leading to the analogous mono- and tram (1,8-) disubstituted cyclam derivatives. 

Table 2 Monosubstituted cyclam derivatives according to Scheme 24...

Chemistry of cyclam derivatives and their complexes was also comprehensively reviewed <2004CSR246>. Some additional information can be found below or in other papers <1998AIC75, 2001AIC293, 2001CCR287, B-2003MI1>. 

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