Cobalt-for-zinc ion substitution

Complexes of nickel(II), copper(II), cobalt(III), zinc(II), iron(II), palladium(II), platj-num(II) and vanadyl can be obtained. Although the reaction sequence is fairly general for metal ions, it is not easily extendable to substituted 2-aminobenzaldehydes. However, 2-amino-5-me-thylbenzaldehyde has recently been used successfully in the macrocyclization reaction.147... 

Although strictly not a dendritic system, Agar et al.[75] have reported the preparation of copper(n) phthalocyaninate substituted with eight 12-membered tetraaza macrocycles as well as its nickel(n), copper(n), cobalt(n), and zinc(n) complexes. Thus, the use of the l,4,7-tritosyl-l,4,7,10-tetraazacyclododecane offers a novel approach to the 1 — 3 branching pattern and a locus for metal ion encapsulation. 

The substitution of cobalt for the native zinc ions of alkaline phosphatase results in an active enzyme with distinctive optical properties, generated by the interaction of cobalt with the ligands of the protein. These properties may be employed to investigate the modes of binding of cobalt to the enzyme and also serve in a remarkable fashion to distinguish the catalytically essential metal atoms from those which play only a structural role. 

The investigation of divalent metal ion-substituted carboxypeptidase A derivatives has shown that the apparent pKa of the high pH ionization is independent of the metal ion. In contrast, the apparent pKa of the low pH ionization changes from 6.33 for the zinc(II) enzyme to 5.57 for the cobalt(II) enzyme when a-N-benzoyl-GlyGly-L-Phe is used as the substrate 151). Although this pH dependence strongly implies that the metal ion directly influences the low pH ionization, the visible spectrum of the cobalt(II) enzyme is not perturbed by this ionization 166). The spectrum of the cobalt(II) enzyme, however, is pH-dependent above pH 8.0. The spectral changes titrate with an apparent pKa of 8.8 166). Note that this value is approximately the same as the apparent pKa which is reflected in the pH-dependence of Am (Fig. 10 c). 

Other Systems.—Dunn has reviewed the mechanisms of zinc-ion catalysis in small molecules and enzymes, and Vallee and co-workers have considered the use of m.c.d. spectra of cobalt(n)-substituted metalloenzymes for determining the coordination number of the metal. 

The preparation, stability and catalytic activity of non-stoichiometric spinel-type phases used in the synthesis of methanol were investigated as a function of the composition, heating temperature and atmosphere. It was shown that these phases formed mainly via amorphous chromates, especially for copper-rich catalysts. High activities in the synthesis of methanol were observed for zinc-rich samples (with a maximum for a catalyst in which 20% of the zinc ions were substituted by copper ions) and associated with the presence of a non-stoichiometric spinel-type phase, stable also in the reaction conditions. On the other hand, the low activity of copper-rich catalysts was attributed to the instability of the spinel-type phase where much of the copper segregates into well crystallized metallic copper, with a further poisoning effect by zinc and cobalt. 

Table I lists isomorphous replacements for various metalloproteins. Consider zinc enzymes, most of which contain the metal ion firmly bound. The diamagnetic, colorless zinc atom contributes very little to those physical properties that can be used to study the enzymes. Thus it has become conventional to replace this metal by a different metal that has the required physical properties (see below) and as far as is possible maintains the same activity. Although this aim may be achieved to a high degree of approximation [e.g., replacement of zinc by cobalt(II)], no such replacement is ever exact. This stresses the extreme degree of biological specificity. The action of an enzyme depends precisely on the exact metal it uses, stressing again the peculiarity of biological action associated with the idiosyncratic nature of active sites. (The entatic state of the metal ion is an essential part of this peculiarity.) Despite this specificity, the replacement method has provided a wealth of information about proteins that could not have been obtained by other methods. Clearly, there will often be a compromise in the choice of replacement. Even isomorphous replacement that should retain structure will not necessarily retain activity at all. However, it has become clear that substitutions can be made for structural studies where the substituted protein is inactive (e.g., in the copper proteins and the iron-sulfur proteins). It is also possible to substitute into metal coenzymes. Many studies have been reported of the...

Many 1,2,4-triazines form complexes with metal ions and can be used for their determination. Thus, 3- and/or 5-(2-pyridyl)-substituted 1,2,4-triazines (e.g. 820) can be used for the determination of iron (II), cobalt(II), nickel(II), zinc(II) and copper(I) ions, thallium and palladium ions can be analyzed by 6-phenyl- (821a) and 5,6-diphenyl-l,2,4-triazine-3-thione (821b), while osmium can be determined by 3-thioxo-l,2,4-triazin-5-one (822), 3-thioxo-dihydro-l,2,4-triazin-5-one (823), 6-mercapto-l,2,4-triazine-3,5-dione (824a), 6-mercapto-5-thioxo-l,2,4-triazin-3-one (824b) and 3,5-dithioxo-l,2,4-triazine-6-carboxyl-ates (825) <78HC(33)189, p. 1004). 

---