Metal-ion insertion

As discussed in Chapter 2, there are a number of important iron-containing enzymes which have neither haem nor Fe-S clusters. While we assume that they get their iron from the LIP, it is not yet established whether or not there are specific enzyme systems involved in the metal-ion insertion. 

The kinetics and mechanism of metal ion insertion into porphyrins has been the subject of a considerable number of studies. As expected, relative to the formation of complexes of flexible macrocycles, such reactions are slow. For the overall reaction M2+ + LH2 ML + 2H+... 

The need for multiple desolvation of the metal ion in some systems may provide a barrier to complex formation which is reflected by lower formation rates - especially for inflexible macrocycles such as the porphyrins. Because of the high energies involved, multiple desolvation will be unlikely to occur before metal-ion insertion occurs rather, for flexible ligands, solvent loss will follow a stepwise pattern reflecting the successive binding of the donor atoms. However, because of the additional constraints in cyclic systems (relative to open-chain ones), there may be no alternative to simultaneous (multiple) desolvation during the coordination process. 

The possible factors involved in the biological selectivity towards metal ions have been considered by Frausto da Silva and Williams3 and by Kustin et al.4 In terms of thermodynamic selectivity a useful formalism for the uptake of any metal ion from a multimetal system is the quotient A Cm, where Km is a relative stability constant and Cm is the concentration of the metal ion. However, as these authors point out,3 a combination of both thermodynamic and kinetic properties must be considered. An appreciation of kinetic factors is often absent in this field, but must be of prime consideration in chelate exchange reactions and in the final irreversible step of metal ion insertion to form the metalloenzymes. 

Hydrogen-bonded supramolecular capsule I compared with coordination capsule II. The external aliphatic groups are omitted for clarity. Note that a pair of intermolecular O—H O hydrogen bonds is replaced by four square-planar Cu-O coordination bonds in the metal-ion insertion process that generates the isostructural inorganic analog. From R. M. McKinley, G V. C. Cave and J. L. Atwood, Proc. Nat. Acad. Sci. 102, 5944-8 (2005). 

The naked metal ion insertion reaction seems to indicate that high M-C bond strengths allow easy C-C bond cleavage for the bare ions. Apparently this is not the case for coordinated metals. Although C-C bond breaking appears to be kinetically facile as the initial step for the unhindered metal complexes, in the case of usual metal complexes, steric congestion at the metal center seems to retard such a process. " C-H activation is generally both thermodynamically and kinetically favored over C-C activation nevertheless, appropriate selection of reaction conditions and catalyst systems may allow C-C activations. " ... 

Thus, with this unsymmetrical ligand, there are two complexes possible with two different metal ions inserted in different compartments. This simple example is sufficient to illustrate the often vast range of options that becomes available when complicated ligands bind to metal ions. However, not all of these options will be equally probable, as the thermodynamic stability of each of the various options will differ, concepts that we will also deal with further in Chapter 5. 

Figure 1. Schematic reaction coordinate diagram comparing the difference between metal atoms and metal ions inserting into a bond as a first step in a chemical reaction. The attractive well of the M(AB) complex can completely offset the insertion barrier if E >E. ...

Understanding of reversible alkali metal ion insertion into oxide materials for cathodes (Mat. Res. Bull., 11 (1976) 83 and J. Power Sources, 1 (1976/1977) 267)... 

Surprisingly, little is known about the pathways involved in metal binding and release in metalloproteins. In particular, there is a lack of information concerning the exchange rates of metal ion insertion in metalloregulatory proteins. Unfortunately, the natural proteins are extremely complex, and individual factors that contribute to the process of metal ion insertion, can be too challenging to identify. It was, therefore, proposed that the helical bundles described here, for which the Cd(II) coordination chemistry is well understood, could be used as models that help clarify some of these questions, and in particular could represent models for Cd(II) insertion into the repressor proteins CadC/CmtR. 

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