The Role of Metal Ion

Because of the limited functional diversity of the available building blocks for polynucleotides the intrinsic reactivity of DNA is in principle restricted, especially in comparison to enzymes. It has been suggested that metal ion cofactors could be 

Two classes of DNAzymes will be discussed in more detail here, namely the DNAzymes catalyzing the cleavage of RNA and the metallation of porphyrins. Other transformations catalyzed by DNAzymes include oxidative DNA cleavage 

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Moustacas, A.-M. Nari, J. Borel, M. Noat, G. Ricard, J. 1991. Pectin methylesterase, metal ions and plant cell-wall extension. The role of metal ions in plant cell-wall extension. Eur. J. Biochem. 279 351-354. 

Since 1960, a very large number of other synthetic macrocycles has been prepared and this has resulted in a great increase in interest in all aspects of the chemistry of macrocyclic systems. From about this time there has also been enhanced interest in the role of metal ions in biological systems and many such bioinorganic studies have involved complexes of both natural and synthetic macrocycles. Thus there has been an element of cross-fertilization between these two developing areas, viz ... 

Choi, W., Termin, A., Hoffmann, M. 1994. The role of metal ion dopants in quantum-sized TiOj. J Phys Chem 98 13669-13679. 

It is generally accepted that the tertiary structures of RNA molecules are stabihzed by metal ions. The roles of metal ions in ribozyme-catalyzed reactions fall into two distinct types the metal ions can act as catalysts during the chemical cleavage step, as shown in Fig. 3, and they can also stabilize the conformation of the ribozyme-substrate complex. 

Grambow, B. 1982. The role of metal ion solubility in leaching of nuclear waste glasses. In Lutze, W. (ed) Scientific Basis for Nuclear Waste Management V. Materials Research Society Symposia Proceedings, 11, 93-102. 

Having determined the metal ion profile, the question is, which metal ions are important enough to the process to warrant control The role of metal ions and the performance of chelants will vary markedly with pH and also with temperature, so it is vital to know the conditions under which a chelant will be used and how this changes with time and/or the reactions taking place. Here reference can be made back to the conditional stability constant graphs (Figure 10.11) to determine if a chelant will be effective at a particular pH. Other chemicals or materials can also interact with metal ions, introduce metal ions into a system, or react with metal ions, so it is important to know what else is in the reaction/ system. Can the chelant cope with the full range of conditions to which it will be exposed ... 

O. (2004) Synthetic metallonucleases for RNA cleavage. Curr. Opin. Chem. Biol., 8, 192. (e) Molenveld, P., Engbersen, J.F.J. and Reinhoudt, D.N. (2000) Dinuclear metallophosphodiesterase models application of calix[4]arenes as molecular scaffold. Chem. Soc. Rev., 29, 75. (f) Kimura, E. (2000) Dimetallic hydrolases and their models. Curr. Opin. Chem. Biol., 4,207. (g) Williams, N.H., Takasaki, B. and Chin, J. (1999) Structure and nuclease activity of simple dinuclear metal complexes quantitative dissection of the role of metal ions. Acc. Chem. Res., 32, 485. (h) Hegg, E.L. and Burstyn, J.N. (1998) Toward the development of metal-based synthetic nucleases and peptidases a rationale and progress report in applying the principles of coordination chemistry. Coord. Chem. Rev., 173, 133. 

The coordination chemistry of the purine-type ligands has been studied on a rather large scale during the last decade, due to its relevance in biological systems. Detailed reviews are available of the coordination chemistry aspects both in the solid state and in solution.146-149 Recently it has also been proposed that the role of metal-ion binding to purines influences the conversions between, for example, B-DNA and Z-DNA.150... 

Several books and review articles are available dealing with various aspects of metal ion atalysis,4 24,29-32 and the role of metal ions in enzymic catalysis.25"28... 

An excellent account of the role of metal ions in the solvolysis of amides and related compounds. 

Last but not least, we should mention that the Society of Biological Inorganic Chemistry (SBIC) was erected in 1995, and is strongly developing, not only giving attention to bioinorganic catalysis, but also to biomimetics, electron transfer, and the role of metal ions in medicine and the environment, including metal-nucleic acid interactions for details, see the website http //www.sbic-home.org/. 

Horseradish peroxidase (and urease) played an important role in the development of the modern concept of the nature of an enzyme and the role of metal ions (Sumner and Somers, 1943 Willstatter, 1965). The species now known as compound II (HRP-II) formed as a result of the reaction of HRP with H202, was discovered in 1937 (Keilen and Mann, 1937). Later compound I (HRP-I), formed prior to HRP-II was identified (Theorell, 1941). The spectra of HRP-I and HRP-II in the 400 nm (Soret band) region have been determined (Chance, 1949 a, b) and measurements have also been extended to the visible region (Chance, 1952). Formation of HRP-I is first order in H202 and HRP (Chance, 1943) and the -OOH group is essential for the oxidation of HRP by peroxide. The enzymatic cycle can be summarised by the following equations (George, 1952),... 

The pathways for hexose and pentose are differentiated mainly through the relative chemical stability of the homologues, glucosepane and pentosinane. The former is a proper AGE under physiological conditions, but the latter is smoothly oxidised to an intermediate, which is subsequently dehydrated to the advanced glycoxidation product, pentosidine. At this stage, it is not known whether oxidation or dehydration is rate determining the role of metal ions needs to be clarified as well. 

Metallic interlayer (MIL) influences the chemical processes of FR. The role of metal ions in the degradation process has been summarized by Lewin and Endo [30], The advantageous effect of a MIL around metal hydroxide flame retardants was utilized at first by Hornsby et al. [31]. They proposed a zinc-hydroxy-stannate (ZnHSt) layer, the detailed chemical-physical structure and 4.7 nm thickness... 

To understand the role of metal ions in hydrolysis reactions, it is useful to first consider the background hydrolysis reactions. Table 6.1 lists the second-order rate constants for hydroxide-catalyzed hydrolysis of various substrates. The reactivity of methyl acetate (first entry in Table 6.1) [16] is comparable to those of other unactivated esters found in nature (e.g. acetyl choline and carboxyl esters in phospholipids). The reactivity of N-methylacetamide (second entry in Table 6.1) [17] is comparable to those of typical peptides (1.1 x 10 6 m-1 s 1) [18] and that of dimethyl phosphate (P-O bond... 

Schwartz and Parks (1974) noted that awareness of the role of metal ions in the oxidation of milk fat has existed since 1905. ft has long been recognized that Cu and Fe are the principal metals involved. Both these metals are normal constituents of milk but may also be present as contaminants concentrations of Cu and Fe in U.S. milk have been reported to be highest in winter and lowest in summer (Murty et al., 1972). Copper is present at a level of 20-400 pg/l and Fe at a level of 100-900 pg/l (Horvat et al., 1965 Koops, 1969 Murty et al., 1972 Johnson, 1974 Jarrett, 1979). However, as noted above, Cu is the principal catalytic metal in lipid oxidation. 

This includes properties of Excited States and photochemical reactions, stmetures of pigments and proteins involved in energy transduction, and in particular the role of metal ions in many of these structures and processes. In most cases, literature references are to recent comprehensive reviews and not to the original publications. 

The carbonyl functionality is one of the most abundant functional groups in biomolecules and pharmaceuticals, including many a- and /3-carbonyl derivatives of ketones and aldehydes and their enol tautomers, which upon deprotonation can form entropy-favored 5-membered (37) and 6-membered (38) chelates with metal ions. In this section, the role of metal ions in the action of some enol-containing biochemicals and pharmaceuticals and the structures of their metal complexes are discussed. 

The involvement of metal ions in the color of anthocyanins and flavonoids was discovered almost a century ago, whereby the different colors of flowers originated from the same molecules under different conditions . The crystal structure of the pigment complex affords better understanding of the color and the role of metal ions , where Fe(III) and Mg(II) bind anthocyanins via the catechol moiety and Ca(II) binds flavone glycosides through a vicinal diol on the glycone. 

TetR and the determination of the role of metal ions in the structure of the TC-M(II)-TetR ternary complex is expected to lead to rational design of TC analogues that exhibit broad-spectrum antibiotic activities yet are devoid of bacterial resistance, such as the third-generation TCs of the glycylcycline family" . 

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