Metal ions Assisting reactions

Another aspect of catalysis at metal ion sites on enzymes is the selectivity exhibited by some enzymes for the type of cation (monovalent versus divalent) and/or the oxidation state (-l- 2 versus + 3) of the cation. Model studies of metal ion-assisted reactions and of metal-ligand structures will be reviewed to establish trends for these types of reactions and features that direct metal ion preference for certain ligand environments. 

It may be instructive to again consider the energetics of a proton transfer reaction of the type involved in the first step of the examples above, in solution. Under the influence of a possible general base as the proton acceptor and a possible metal ion assisting as a catalyst we can write... 

Carbonic anhydrase is a zinc(II) metalloenzyme which catalyzes the hydration and dehydration of carbon dioxide, C02+H20 H+ + HC03. 25 As a result there has been considerable interest in the metal ion-promoted hydration of carbonyl substrates as potential model systems for the enzyme. For example, Pocker and Meany519 studied the reversible hydration of 2- and 4-pyridinecarbaldehyde by carbonic anhydrase, zinc(II), cobalt(II), H20 and OH. The catalytic efficiency of bovine carbonic anhydrase is ca. 108 times greater than that of water for hydration of both 2- and 4-pyridinecarbaldehydes. Zinc(II) and cobalt(II) are ca. 107 times more effective than water for the hydration of 2-pyridinecarbaldehyde, but are much less effective with 4-pyridinecarbaldehyde. Presumably in the case of 2-pyridinecarbaldehyde complexes of type (166) are formed in solution. Polarization of the carbonyl group by the metal ion assists nucleophilic attack by water or hydroxide ion. Further studies of this reaction have been made,520,521 but the mechanistic details of the catalysis are unclear. Metal-bound nucleophiles (M—OH or M—OH2) could, for example, be involved in the catalysis. 

Barefield, E. K., Wagner, F., Hodges, K. D., Synthesis of macrocyclic tetramines by metal-ion assisted cyclization reactions. Inorg. Chem. 1976,15, 1370-1377. 

What we found is that all metal ions catalyze P—O fission. Selective P—O fission by amines was increased from 80% to 100% in the presence of Mg2+ ion, which also enhanced the rate. Exclusive P—O fission also occurred in the attack by the oxyanion of PCA in the presence of Zn2+ ion. A plausible rationale is that such a path, which involves metal ion assistance in a pentacovalent intermediate as illustrated in Figure 12a, is energetically much more favorable than that of Sn2 displacement on sulfur. Conversely, if an enzyme that catalyzes the reaction of phosphosulfate is metal ion dependent, the reaction probably involves P—O fission, as suggested by Roy (4). 

Myriad polydentate aza-macrocycles have been reported 41. The extent of the subject forces limitation of this discussion to only macrocycles containing a pyridine or dipyridine subunit. Most of these coronands have been synthesized by a SchifF base condensation of an aldehyde or ketone with a hfc-primary amine in the presence of a metal ion. The metal ion acts as a template, resulting in dramatic increases in yield of the desired cyclic product over linear polymerization products42 46. Lindoy and Busch45 have described this effect in two ways, kinetic and thermodynamic. If the metal ion controls the steric course of a series of stepwise reactions, the template effect is considered to be kinetic. If the metal ion influences an equilibrium in an organic reaction sequence by coordination with one of the reactants, the template effect is termed thermodynamic. It is the kinetic effect that is believed to be operative in most metal ion-assisted (in situ) syntheses of... 

Terpene synthases, also known as terpene cyclases because most of their products are cyclic, utilize a carbocationic reaction mechanism very similar to that employed by the prenyltransferases. Numerous experiments with inhibitors, substrate analogues and chemical model systems (Croteau, 1987 Cane, 1990, 1998) have revealed that the reaction usually begins with the divalent metal ion-assisted cleavage of the diphosphate moiety (Fig. 5.6). The resulting allylic carbocation may then cyclize by addition of the resonance-stabilized cationic centre to one of the other carbon-carbon double bonds in the substrate. The cyclization is followed by a series of rearrangements that may include hydride shifts, alkyl shifts, deprotonation, reprotonation and additional cyclizations, all mediated through enzyme-bound carbocationic intermed iates. The reaction cascade terminates by deprotonation of the cation to an olefin or capture by a nucleophile, such as water. Since the native substrates of terpene synthases are all configured with trans (E) double bonds, they are unable to cyclize directly to many of the carbon skeletons found in nature. In such cases, the cyclization process is preceded by isomerization of the initial carbocation to an intermediate capable of cyclization. 

The core of the palm domain of Polr/ includes a four-stranded antiparallel j3 sheet flanked by two small a helices and an a-helical structure situated at the base of the palm, which is superimposable with the core of the palm domain from high-fidelity polymerases. Akin to the active sites of the polymerases from the A-, B-, C-, and X-families, the palm domain of Polr/ contains three carboxylates (Asp30 and Aspl55-Glul56), which coordinate two catalytically essential metal ions assisting the nucleotidyl transferase reaction. Although the palm subdomain is nearly superimposable... 

More closely related to kinetics and mechanism are three reviews from Danish chemists, one on the state of the art with respect to Cr(III) substitution reactions and the other two ° survey /t-diol dinuclear Cr(III) systems. Chromium chemistry is also discussed in a general review on metal-ion-assisted aquation reactions " and in a review on the effect of pressure on reaction rates. In the following sections, units for and AH are in kJ mol A5 in J K mol A V in cm mol visible absorption spectral maxima (A ax) in nm, and molar extinction coefficients (e) in cm Unless otherwise stated, all rate constants are reported at 25.0 (298.2 K). 

In many metal ion-assisted hydrolytic peptide bond cleavage reactions, the metal ions, such as Pd, Pt, Cu, Mo, and Ni, are trapped by hydrolyzed products. Because free metal ions that are reactive for peptide bond hydrolysis hardly regenerate, examples for metal ion-catalyzed peptide bond cleavage are Umited. 

Initiation formation of the primary source of radicals is usually brought about through homolytic fission, photo-excitation, and transition metal ion assisted redox reactions. 

The primary role of antioxidants is to prevent or inhibit degradation induced by free radical reactions. Antioxidants function via the reactions discussed earlier. The two reactions that are most prevalent in antioxidant function are hydrogen abstraction and metal ion assisted electron transfer. 

Metal ion assisted electron transfer reactions are important when considering the roles of sequesterants and enzymes in antioxidant protection (8). Compounds like ethylenediaminetetraacetic acid (EDTA), phytic acid, and polyphenols can sequester transition metal ions and thereby inhibit oxidation. Binding the metal ions essentially prevents them from regenerating hydroxy radicals through the Fenton reaction. 

The thiazole-to-formyl conversion entails a three-step reaction sequence Af-methylation to an fV-methylthiazolium salt, then hydride reduction to thiazohdine, and finally metal-ion-assisted hydrolysis to aldehyde. This latter step can be performed with CuCl2-CuO (introduced by Dondoni and coworkers) or AgNOs... 

Although PI is a plausible intermediate on the reaction path in such reactions, it has not been detected directly by experiment and, hence, its proposed existence remains largely speculative. However, indirect proof for the presence of PI on the reaction path comes from the observed isomerization between 3, 5 -Unkage and 2, 5 -linkage only under acidic pH where PI can exist in the monoanionic form (PIH). Thus, an alternative mechanism (Scheme 2.26) for the metal-ion-assisted hydroxide-ion- and general base ( B)-catalyzed hydrolysis of RNA and RNA-model compounds cannot be completely ruled out if pentacoordinated intermediate (PIH) does exist on the reaction path. Nearly 10 -fold enhanced catalytic effects of Co " complexes are attributed to the occurrence of intramolecular electrophilic catalysis as shown in the transition state TS,g. 

This reaction is catalysed by traces of heavy metal ions such as Cu and the purpose of the gelatin is to suppress reaction (5) by sequestering the metal ions it is probable that gelatin also assists the hydrazine-forming reactions between ammonia and chloramine in a way that is not fully understood. The industrial preparation and uses of N2H4 are summarized in the Panel. 

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