Macrocycle complex formation

A very large number of synthetic, as well as many natural, macrocycles have now been studied in considerable depth. A major thrust of many of these studies has been to investigate the unusual properties frequently associated with cyclic ligand complexes. In particular, the investigation of spectral, electrochemical, structural, kinetic, and thermodynamic aspects of macrocyclic complex formation have all received considerable attention. 

As has been mentioned previously, the approach to equilibrium can often be slow for macrocyclic complex formation indeed, equilibrium may take days, weeks or even months to be established. This may give rise to experimental difficulties in conventional titration procedures. Under such circumstances, it is usually necessary to carry out batch determinations in which a number of solutions, corresponding to successive titrations points, are prepared and equilibrated in sealed flasks. The approach to equilibrium of each solution can then be monitored at will. 

Since we shall not obtain the comparable amount of detailed information on the mechanisms of substitution in octahedral complexes from the studies of more complicated substitutions involving chelation and macrocycle complex formation (Secs. 4.4 and 4.5) it is worthwhile summarizing the salient features of substitution in Werner-type complexes. 

Cox. B.C. Schneider, H. Kinetics and mechanism of macrocyclic complex formation. Pure Appl. Chem. 1990. 62 (12). 2259-2268. 

The stabilization of the 1+ oxidation state may be realized by the encapsulation of metal ions into the cavity of macrocyclic ligands containing azomethine or thioether groups. Only one Fe macrocyclic complex has been described in the literature (5). Since 1972 no reports concerning the stabilization of Fe by macrocyclic complex formation have appeared in the literature. 

Bradshaw and his coworkers have listed several motivations for their explorations in this area. One objective of [the] research program is to prepare and study a series of multi-dentate compounds which resemble naturally occurring macrocyclic compounds . Further, Bradshaw and his coworkers have said that it is our hope that we can prepare macrocycles to mimic the selectivities of the naturally occurring cyclic antibiotics and thereby make available models for the investigation of biological cation transportation and selectivity processes . These workers have presented a number of comparisons with valinomy-cin . The other expressly stated goal of their research is to prepare molecules which will allow us to systematically examine the parameters which affect complex stability and to understand that stability in terms of AH and TAS values for complex formation . 

As a final example we consider noncovalent molecular complex formation with the macrocyclic ligand a-cyclodextrin, a natural product consisting of six a-D-glucose units linked 1-4 to form a torus whose cavity is capable of including molecules the size of an aromatic ring. Table 4-3 gives some rate constants for this reaction, where L represents the cyclodextrin and S is the substrate ... 

Macrocyclic effect and specific character of complex formation with porphyrins 97MI8. 

Structure-chemical aspects of complex formation in metal halide-macrocyclic polyether systems 99UK136. 

Problems of complex formation with macrocyclic ligands. S. L. Davydova and N. A. Plate, Coord, Chem. Rev., 1975,16, 195-225 (130). 

Scheme 1. Formation of a macrocyclic complex between a diboronic acid and a saccharide...

Cyclodextrins can solubilize hydrophobic molecules in aqueous media through complex formation (5-8). A nonpolar species prefers the protective environment of the CDx cavity to the hulk aqueous solvent. In addition, cyclodextrins create a degree of structural rigidity and molecular organization for the included species. As a result of these characteristics, these macrocycles are used in studies of fluorescence and phosphorescence enhancement (9-11), stereoselective catalysis (.12,13), and reverse-phase chromatographic separations of structurally similar molecules (14,15). These same complexing abilities make cyclodextrins useful in solvent extraction. 

Complex formation between a metal ion and a macrocyclic ligand involves interaction between the ion, freed of its solvation shell, and dipoles inside the ligand cavity. The standard Gibbs energy for the formation of the complex, AGjv, is given by the difference between the standard Gibbs... 

Complexation and determination of formation constants has been studied with the tetramethyl-cyclam (l,4,8,ll-tetramethyl-l,4,8,ll-tetraazacyclotetradecane) ligand.686 A series of zinc N4 donor macrocyclic complexes with different ring sizes were synthesized and characterized for comparison with cadmium derivatives.687... 

C NMR studies suggest that 1,4,7,10-tetra-azacyclododecane-l,7-diacetic acid binds to zinc in a cis octahedral geometry—the two carboxylate oxygens are cis and the remaining four donors from the cyclen macrocycle. The formation constant was determined for the complex.733... 

It was shown that 2,5-bis(phenoxy)-3,3aA4,4-trithia-l,6-diazapentalene 182 reacts with , v-diami nopolyether nucleophiles 183 in a 1 1 molar ratio to form novel pentaleno crown ethers 184 (see Scheme 21 and Table 24) <1997AG(E)1648>. Macrocycles 184 were readily reduced by treatment with zinc in acetic acid to form the corresponding thioureas 185. The reoxidation is quantitative in the presence of atmospheric oxygen. The complex formation of the starting pentalene 182 and the new crown ether compounds 184 and 185 was investigated (see Section 12.11.7.2). 

Complex stability constants are most often determined by pH-potentiometric titration of the ligand in the presence and absence of the metal ion.100 This method works well when equilibrium is reached rapidly (within a few minutes), which is usually the case for linear ligands. For macrocyclic compounds, such as DOTA and its derivatives, complex formation is very slow, especially for low pH values where the formation is not complete, therefore a batch method is... 

The zinc(II) complexes of meso-tetraphenyltetrabenzoporphyrin (38) and of meso-tetraphenyl-tetranaphthoporphyrin (39) have been prepared 173-175 some photophysical properties of this interesting series are given in Table 11176 Photooxidation of zinc(II) porphyrins causes cleavage of the macrocycle with formation of bilinone derivatives.122 206 207... 

Condensation of 2,6-diacetylpyridine with bis(3-aminopropane)amine in the presence of small ions such as Mn(n), Co(n), Ni(n) or Cu(n) readily leads to formation of the corresponding monomeric (14-membered) macrocyclic complexes of ligand (83). However, when the large Ag(i) ion is used as the template, then a dimetallic complex of a 28-membered macrocycle of type (88) is produced. This example illustrates well the importance of metal-ion size in promoting template reactions. 

A feature of the metal-ion chemistry of these large ring macrocycles is thus the structural diversity which may occur from one system to the next. This diversity can result directly from small changes in the structure of the cyclic ligand and is also aided by the inherent flexibility of the large rings involved. It is clearly also influenced by the nature of the other ligands available for complex formation. 

In the preceding chapter, thermodynamic aspects of macrocycle complexation were treated in some detail. In this chapter, kinetic aspects are discussed. Of course, kinetic and thermodynamic factors are interrelated. Thus, in terms of a simple complexation reaction of the type given below (charges not shown), the stability constant (/CML) may be expressed directly as the ratio of the second-order formation constant (kf) to the first-order dissociation rate constant (kd) ... 

---