Metal chelates bifunctional

Certain bifunctional metal chelating agents have been used to investigate protein interactions by virtue of their ability to generate reactive oxygen species that affects protein structure in the immediate vicinity of their modification site. The following sections discuss two applications of such chelate labels, one of which cleaves peptide bonds while the other one causes covalent crosslinks to occur between interacting protein structures. 

Chelating agents, 5 708-739 12 61, 122 applications, 5 731-732 bifunctional, 5 7236 classes of, 5 712-713t concentration formation constants of metal chelates, 5 717t cyanide applications, 8 183 dispersants contrasted, 8 686 economic aspects, 5 729-730 environmental, health, and safety factors, 5 731... 

Figure 6. Three bifunctional metal chelates substituted cryptand, bifunctional EDTA, and DTPA.

There are two methods the preformed radiometal-chelate method and the indirect chelator—antibody method. Various antibodies are labelled by the latter, where the bifunctional chelating agent is initially conjugated to a macromolecule, which is then allowed to react with a metal ion, to form a metal-chelate-macromolecule complex. Due to the presence of the chelating agent, the biological properties of the labeled protein may be altered and must be assessed before clinical use. 

If the monohydroxy chelate is considered the reactive species, it is possible that it would react as a bifunctional catalyst, as is indicated by formula III, wherein the metal chelate donates a hydroxyl group to the substrate while simultaneously assisting in the removal of the fluoride ion by coordination. Another possibility would involve coordination of the complex with the negative oxygen rather than with the fluoride ion. The term push-pull mechanism has been employed to describe this type of function. 

As an alternative to the highly specific catalysis indicated by formulas I, II, and III, it is possible that the metal chelate compound merely participates in a generalized type of acid-base catalysis. Thus, the function of the metal would be to increase the acidity of the substrate through molecular association and thereby increase its susceptibility toward attack by other bases present such as hydroxide ion or water molecules. Under these conditions the diaquo chelate A would be an acid catalyst, the monohydroxy chelate Bi would be considered to be bifunctional in its effect, and the dihydroxy chelate B2 would probably be a weak basic catalyst. 

Remy S, Reilly R M, Sheldon K, et al. (1995). A new radioligand for the epidermal growth-factor receptor—In-111 labeled human epidermal growth-factor derivatized with a bifunctional metal-chelating peptide. Bioconj. Chem. 6(6) 683-690. 

The binding sites of platinum to DNA and its separate bases are expected to be similar to those for the other -metals, provided that the platinum binds through one site only. However both PtClf- and such molecules as Pt(NH3)2Cl2, cis- and trans-iorms, can act bifunctionally. Indeed preferential binding is expected to yield chelated complexes of one type or another. For example the cis-chelation will lead to the following complexes. 

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