Cyclam, conformations

With respect to the ring size, it has been stated that neither the redox potentials nor the half-lives of the Ni species are directly correlated to the cavity of the macrocyclic ligand, but the redox potentials are dependent on solvation effects.139 The effect of fused benzene rings and ring conformation has been monitored.140 In Ni complexes of fluorine-containing cyclams (25) the higher oxidation state becomes successively destabilized with respect to Ni, while the lower oxidation state (i.e., Ni1) becomes successively stabilized.141... 

In addition to the charge control over the reaction discussed above, there is also a marked element of conformational control over alkylation reactions. This is seen clearly in the methylation of the nickel(n) complex of the tetraaza macrocyclic ligand, cyclam (Fig. 5-32). Reaction of the nickel complex with methylating agents allows the formation of a A, A V",A "-tetramethylcyclam complex. In this product, each of the four nitrogen atoms is four-co-ordinate and tetrahedral, and specific configurations are associated with each. Of the four methyl groups in the product, two are oriented above the square plane about the nickel, and two below it. 

Figure 5-32. The methylation of a nickel(n) cyclam complex to give one specific conformer of the N, N, N", yV"-tetramethylcyclam complex.

The non-linear spectral changes of the naphthyl-localised exciplex and exci-mer bands occur after addition of the first two equivalents of trifluoroacetic acid. It is thus unnecessary to protonate all of the nitrogen atoms in order to suppress exciplex formation since - expressed figuratively - the nitrogen atoms share the protons. Moreover, protonation not only provides protection against exciplex formation but also leads to conformational changes in the cyclam unit itself, which in turn affects excimer formation between peripheral naphthyl units of the dendrimer. 

Cyclam, or 1,4,8,11-tetraazacyclotetradecane, was first synthesised, inadvertently, by van Alphen in 1937 through the reaction of 1,3 bis (2 aminoethyl)-aminopropane with 1,3 dibromopropane. The first major studies of the ligand by Bosnich et al. used X-ray crystallography to elucidate different conformations of the metal complexes of the macrocycle.27 Their synthesis was similar to van Alphen s procedure, but did not involve a template method and as a result yields were unimpressive. They showed that five out of the possible ten different metal-complex conformers exist in the solid-state (Figure 3.51). 

Figure 3.51 The five most stable conformers of cyclam (M= transition metal, X=coordinating anion, R = H, Me etc).

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. 

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