Metallic ions, effect

Metal ions, effect of size, 200-205 Metalloenzymes, see also Enzyme cofactors classification of, by cofactor and coupled general base, 205-207, 206 electrostatic interactions in, 205-207 SNase, 189-197... 

The increase in energy content of an atom, ion, or molecular entity or the process that makes an atom, ion, or molecular entity more active or reactive. In enzymology, activation often refers to processes that result in increased enzyme activity. For example, increasing temperature often can have a positive effect on enzyme activity (See Arrhenius Equation). Other examples of enzyme activation include (1) proteolysis of zymogens (2) alterations in ionic strength (3) alterations due to pH changes (4) activation in cooperative systems (5) lipid or membrane interface activation (6) metal ion effects (7) autocatalysis and (8) covalent modification. 

On the basis of the structural and metal ion effects, it is postulated that the transition states of the hydrolyses which are catalyzed by calcium, barium, cobaltic, and thallous ions can be represented by the chelate structures ... 

Several earlier studies [3-6,8] clearly showed that enhanced metal ion effects on rates of ester cleavage are obtained in model substrates in which a covalently linked polyether chain holds the metal ion in close proximity to the ester function undergoing nucleophilic attack. 

Kraft, D., Cacciapaglia, R., Bohmer, V.. El-Eadl, A.A., Harkema, S., Mandolini. L., Reinhoudt, D.N., Verboom, W. and Vogt, W. (1992) New crown ether-like macrocycles containing a nitrophenol unit. Synthesis and metal ion effects on the reactivity of their acetates in transcylation reactions. J. Org. Chem., 57, 826. 

One possible mechanism for the hydrolysis of peptides or esters by carboxypeptidase A involves two steps with an anhydride (acyl-enzyme) intermediate.418 In the first step, the zinc(II) activates the substrate carbonyl group towards nucleophilic attack by a glutamate residue, resulting in the production of a mixed anhydride (127). Breakdown of the anhydride intermediate is rate determining with some substrates.419 An understanding of the chemistry of metal ion effects in anhydride hydrolysis is therefore of fundamental importance in regard to the mechanism of action of the enzyme. Until recently there have been few studies of metal ion-catalysed anhydride solvolysis. 

L. Wu et al., Ligand and metal-ion effects in metal-ion clusters used for chiral analysis of a-hydroxy acids by the kinetic method. Anal. Bioanal. Chem. 373, 618-627 (2002)... 

Further studies on these protein-pyridoxamine conjugates were devoted to the turnover behaviors, metal ion effects, and effects of pyridine quaternization [34], As many... 

Metal Ion Effects. The metal ion effects on the acid-catalyzed hydrolysis of PPS also were examined by Benkovic and Hevey (5). However, they observed that in water near pH 3, the rate enhancement in the presence of an excess of metal ion was at most only threefold (Mg2+, Ca2+, Al3+) and in some cases (Zn2+, Co2+, Cu2+) the rate was actually retarded. We thought that the substrate PPS and Mg2+ ion should be hydrated heavily in water so that their complexa-tion for rate enhancement is weak. If, however, the hydrolysis is carried out in a solvent of low water content, such complexation would not occur, and therefore, the rate enhancement might be more pronounced. This possibility appears to be supported by the fact that the active sites of many enzymes are hydrophobic. Of course, there is a possibility that the S—O fission may not require metal ion activation. In this connection, it is interesting to note that in biological phosphoryl-transfer reactions the enzymes generally require divalent metal ions for activity (7, 8, 9), but such metal ion dependency appears to be less important for sulfate-transfer enzymes. For example, many phosphatases require metal ions, but no sulfatase is known to be metal... 

The rate maxima of Figure 4 suggest that the substrate can be activated through the formation of a 1 1 complex with metal ion. Unfortunately, it was difficult to determine whether chelation occurs on the P—O group, the S—O group, or both. Another problem was the complicated dependency of this metal ion effect on acid concentration. Furthermore examination of this system under neutral conditions was not successful and failed to give reproducible results, because of the very slow rate even in the presence of Mg2+ ion. 

Metal Ion effect. Divalent metal ions (Mg2+, Co2+, Zn2+, Ni2+) catalyzed the above nucleophilic reaction on the phosphorus atom. The yields of phosphoramidate and inorganic sulfate become 100% in the presence of Mg2+ ion. In Figure 7 are shown the effect of Mg2+ ion on the reaction of imidazole. In this case, imidazole acts as nucleophilic catalyst. The figure shows that the kohs values tend to deviate from the first-order dependency on Mg2+ ion at high metal ion concentration, suggesting the complexation of substratje with metal ion. 

These data indicate a very large metal ion effect. Thus, the nucleophilic reactivities of imidazole and oxime anion toward the phos-phoryl group are enhanced by Mg2+ to 41- and more than 746-fold, respectively, in water. The combined effect of metal ion and nucleophile may amount to some 104-106-fold rate enhancement when compared with the water rate (-TO-5 min-1) Such effects would be even larger in the solvents of low water content and they may be very good models of phosphatase activity. However, they do not answer our question for the activation mechanism of S—O fission under neutral conditions. 

Metal Ion Effect Complexation of PMPS with Zn2+ ion could be observed by the decrease of absorption intensity of the pyridine ring (Figure 20b). A similar decrease was observed for the parent pyridyl-methylphosphonate (Figure 20b). Therefore, the 1 1 complex in which a metal ion is bridged between pyridyl nitrogen and phosphoryl oxyan-ion likely is involved (Figure 16a). Meanwhile, no detectable change of spectrum was observed in the case of Mg2+ ion, in accordance with very weak chelation of Mg2+ ion with a pyridine base. 

Figure 21. Metal ion effect on the acid hydrolysis of phosphosulfate (a) electrophilic catalysis and (b) metal-ion-assisted, proton-transfer catalysis...

Figure 23. Hypothetical metal ion effect on the hydrolysis of polyphosphate (26).

Photoelectron spectroscopy (PES) has been shown to provide a convenient probe of metal ion effective nuclear charge and the nature of the metal-ligand bond via the energy of valence-electron photoionizations (16, 20, 22, 284, 285, 312, 332-334). Recently, PES spectroscopy has been employed in the study of oxo-molybdenum compounds of the type (L-A5)MoE(X,Y) [E = O, S, NO X, Y = halide, alkoxide, or thiolate] in order to evaluate the synergy between the axial (E) and equatorial (X,Y) donors in affecting the ionization energy of the HOMO localized on the Mo center (16, 284, 334). These studies have conclusively shown that equatorial dithiolene coordination electronically bulfers the Mo center in (L-A pMoEttdt) (Fig. 13) from the severe electronic perturbations associated with the enormous variation in the Ji-donor/acceptor properties... 

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