Activated zinc

Ma L.Q., Lindsay W.L. Divalent zinc activity in arid-zone soils by chelation. Soil Sci Soc Am J 1990 54 719-722. 

Near surface neutralization of Zn in bare InP Zn has also been reported after CH4/H2 reactive ion etching. In this particular case a one minute annealing at 350°C restores the zinc activity (Hayes et al., 1989). 

Reduction of enynes to (Z)-atkenes. Lindlar s catalyst is not useful as a hydrogenation catalyst for reduction of trienynes or of dienediynes. The best results can be obtained in CH3OH with zinc activated by successive treatment with Cu(OAc)2 (10%) and AgN03 (10%). This reduction results in conversion of the triple bond to a (Z)-double bond. The system does not reduce simple, nonactivated alkynes, and a-branched enynes are reduced slowly. The reduction is effected at 25° with (Z)-enynes, but temperatures of 45° are necessary for the (E)-isomers. Yields of pure tetraenes are 25-65%. 

Aldol condensation of chlorodifluoromethyl ketones with ketones can be effected in moderate yield by use of diethylaluminum chloride (1.1 equiv.) and zinc activated with silver (I) acetate. 

Zinc, cyclopropane from 1,3-dichloropropane, 51, 58 Zinc, activated, 53, 88 Zinc chloride, anhydrous, ethereal solution, preparation of, 54, 54... 

Amino(alkoxycarbonyl)methylenemalonates (314) were also prepared in good yields in the reactions of dialkyl cyanoformate and bromo- or chloromalonates in the presence of SnCl2 or TiCl3 in benzene, or in the presence of zinc activated by copper in THF, [81JAP(K)71049, 81JAP(K)87542]. 

Trispyrazolylborates are models for tris-histidine active sites in zinc enzymes, e.g., the matrix metalloproteinases involved in breakdown of extracellular matrices. Inhibition of these metalloproteinases may prove valuable in the treatment of, inter alios, cancer and arthritis, so efforts are being made to find appropriate ligands to block the zinc active site. The search has recently moved on from hydroxamates to hydroxypyridinones - l-hydroxy-2-pyridinone is a cyclic analogue of hydroxamic acid. As reported in Section II.B.2 earlier, hydroxypyridinones form stable five-coordinate complexes on reaction with hydrotris(3,5-phenylmethylpyrazolyl)borate zinc hydroxide. Modeling studies suggest that hydroxypyridinonate ligands should be able to access the active site in the enzyme with ease (110). 

Fig. 11. The slowly hydrolyzed substrate glycyl-L-tyrosine binds to carboxypeptidase A in a nonproductive complex where the amino-terminal glycine complexes the active-site ion (large sphere) to form a five-membered chelate, as in Fig. 10. Protein-bound zinc ligands Glu-72, His-69, and His-196 complete the coordinadon polyhedron of pentacoordinate zinc. Active-site residues are indicated by one-letter abbreviadons and sequence numbers E, glutamate H, hisddine R, arginine Y, tyrosine. [Reprinted with permission from Christianson, D. W., Lipscomb, W. N. (1986) Proc. Natl. Acad. Sci. U.S.A. 83,7568-7572.]...

The corresponding cross-coupled products are obtained in excellent yields (98%) when the reactivate zinc is prepared in the presence of naphthalene. Interestingly, the yield falls down to 19% in the absence of mediator whereas no product was obtained from commercial zinc activated by an acidic solution. 

Anyway, this massive zinc activation process has been successfully used to achieve a number of reactions which usually require more delicate and uncertain zinc activation processes. 

As for the above-mentioned reactions, the reaction rate can be accelerated if a low additional reduction current is applied after the electrochemical zinc activation. 

Nevertheless, this electrochemical zinc activation procedure, which looks like the chemical activation developed by Rieke, does not appear to be very convenient for the electrochemical synthesis of organozinc compounds in one step (equation 24) without preparation of the active zinc in a preliminary step4,13. 

B). It has been reported that there are either three (163) or two (164) potential wells for CO2 in the hydrophobic pocket. Site-directed mutagenesis results indicated that when Val-143 is replaced by the much larger Phe, the activity decreases by a factor of 103 (128b). This is rationalized in terms of less space available within the cavity to accommodate C02 because of the relatively larger Phe residue. It has also been reported that CCVs interactions with positive charges around zinc activate the carbon for nucleophilic attack (165). Merz reported that the positioning of C02 between zinc and the peptide NH of Thr-199 would be ideal for neucleophilic attack by hydroxide (164). 

Recently, Cottam and Ward (182) found that with the titration of apo-alkaline phosphatase with Zn(II) up to a mole ratio of four Zn(II/ dimer results in no increase in the S5C1 NMR linewidth, .. . while in previous studies of zinc activated biological reactions, a large increase in the chloride linewidth was observed with zinc bound to macromolecules. However, an increase in the chloride linewidth is observed when the pH is decreased below 5.0. This was interpreted as showing that Zn(II) in alkaline phosphatase is not exposed to solvent at pH > 5.0. In an ESR study of Cu(II) binding to alkaline phosphatase, Csopak and Falk (133) reported that two Cu(II) binds to the same specific sites as the two Zn(II), that the ESR spectrum for the one copper enzyme is different from the two copper enzymes, and that phosphate binding causes a shift of the spectral lines. 

A fully concerted mechanism for reaction 299 has been eliminated as inconsistent with 14C and 15N KIEs and also with the observed inverse solvent D2O effect. The reaction path for the deamination of AMP has been formulated613 as a stepwise conversion involving the formation of tetrahedral intermediate 515 characterized by full-bonded hydroxyl and amino groups (equation 300). The TS for slow formation of 515, resulting from the attack of the hydroxyl from enzyme zinc-activated water at the C(6), is characterized by the C(6) OH bond order of 0.8 0.1 (late TS) and fully bonded NH2, that is by the nearly complete conversion to sp3 at C(6), and by nearly complete protonation of Nq), 516, The protonation of NH2 (in 515) and departure of NH3 (with TS 517) take place in the subsequent rapid steps as shown in equation 300, Zinc hydroxide is formed prior to attack514 at C(6). Enzymatic degradation of [6-14C]AMP has been carried out to prove the position of the radiolabel in 513 (equation 301). No radioactivity in the allantoin... 

Co-ordination of the ligand to the zinc activates it towards nucleophilic attack by ammonia and the product is the zinc complex of a conjugated dianionic tetraaza macrocycle (Fig. 8-35). This ligand is of some interest in forming a very stable lithium complex, derivatives of which have found some application in photoaddressable devices. 

E,E,Z)-Trienes.1 Zinc activated by Cu(OAc)2 and AgN03 effects stereoselective reduction of the dienyne 1 to the (E,E,Z)-triene 2 in CH30H/H20. Catalytic hydrogenation using Lindlar s catalyst gives 2, but only in 30% yield. 

These methods of zinc activation complement the known chemical methods and are useful efficient alternatives, since no excess of halide or reducing agent is required, and the electrochemical setting is very simple. They are unfortunately not preparatively convenient for aromatic halides. Such a reaction (Equation 8.16) has been reported,13 but the yields of arylzinc reagent are quite low when expressed on the basis of the starting aryl halide instead of the amount of zinc dissolved. 

However, zinc activation becomes exceedingly important as soon as less... 

Garner and Behai have reported the isolation of a zinc-activated aminopeptidase from human liver.231 The enzyme, which is capable of forming a cobalt-enzyme complex, has zinc located at or near the substrate binding site. 

Studies on the various zinc-activated dehydrogenases continue apace. The reduction of tra s-4-iViV-dimethylaminocinnamaldehyde (A) by liver alcohol dehydrogenase (LADH) is reported to involve the zinc at the active site of the enzyme acting as a Lewis acid and co-ordinating the substrate via the aldehyde oxygen.235 The kinetics of the reaction show that (A) 4- LADH -f NADH form a stable intermediate at pH 9, the overall reaction sequence being ... 

Metallohydrolases are the third major class of hydrolytic enzymes. Unlike serine or cysteine hydrolases, the metallohydrolases achieve substrate hydrolysis via a zinc-activated water molecule [78-80] (Scheme 3). 

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