Cleavage mechanisms copper ions

Pathway 1 may not be relevant to Tyr catalysis homolytic cleavage of the peroxide O—O bond is presumably not the case in Tyr because the two copper ions are held by the protein chains so as to reverse the O—O bond cleavage. But pathway 2 can occur in Tyr as well. A proposal for the mechanism of Tyr is illustrated in Fig. 22. In Tyr, only one phenol can be inserted into the substrate-binding pocket in the protein,... 

Thus, there has been interest concerning whether it is the former or the latter species actually affecting the phenol oxygenation. And in fact. Stack, Solomon, and co-workers reported on a system where they could definitively show that phenol o-hydroxylation occurs from a bis-(/a-oxo)-dicopper(III) complex via an electrophilic mechanism (Fig. 3) (60). Their chemical-spectroscopic and recent theoretical (63) studies show that the binding of a phenolate substrate to a copper ion leads to 0—0 bond cleavage in an initially formed f-peroxo-dicopper(II) complex, generating the active Cu(lll)2-(0)2 moiety (Fig. 3) (60). Casella (64) also more recently reported on a similar finding. 

The commonest reactions involve the displacement of halide by hydroxide or cyanide ion to yield co-ordinated phenols or nitriles. Once again, the metal may play a variety of different functions. The polarisation of the C-Cl bond is the most obvious, but stabilisation of the product may be of equal importance, as could the involvement of a metal coordinated nucleophile. The availability of a one-electron redox inter-conversion between copper(n) and copper(i) also opens up the possibilities of radical mechanisms involving homolytic cleavage of the C-Cl bond. All of these different processes are known to be operative in various reaction conditions. In other cases, organocopper intermediates are thought to be involved. 

The modulation of the coordination to the transition metal has not necessarily positive implications on the reactivity. For instance, we observed [50] that the copper(II) complex (8) of tetramethyl-l,2-diaminoethane catalyzes the hydrolysis of the phosphoric acid triester PNPDPP via an electrophilic mechanism which involves the pseudointramolecular attack of deprotonated water, as illustrated in (9). The electrophilic mechanism contribution to the hydrolytic process totally disappears in micellar aggregates made of the amphiphilic complex (10). Clearly, micellization does not allow the P O group of the substrate to interact with the metal ion. This could be a result of steric constraint of the substrate when bound to the micelle and/or the formation of binuclear dihydroxy complexes, like (11), in the aggregate. So, in spite of the quite large rate accelerations observed [51] in the cleavage of PNPDPP in metallomicelles made of the amphiphilic complex (10), the second-order rate constant [allowing for the difference in pXa of the H2O molecules bound to copper(II) in micelles and monomers] is higher for (8) than for (10) (k > 250). 

A combination of kinetic and labeling studies established a mechanism involving attack by copper-bound hydroxide, followed by PO bond cleavage. Further details of the mechanisms of these reactions has come from a detailed study of the hydrolysis of ci5-[Ir(en)2(0H) 0P(=0)(0R)2 ] (36) complexes (R = ethyl or 4-nitrophenyl). The reaction involves intramolecular attack by coordinated hydroxide, and rate enhancements of 10 are found. The products of the reactions are not the chelated phosphate esters (37) expected from a knowledge of cobalt(III) chemistry, but monodentate phosphate monoesters (38). This is assigned to relative differences in the sizes of the metal ions and the basicity of the coordinated... 

In view of the requirement for metals in all cells, the optimum concentration for a virus may be different from that of the host cell and specific inhibition of the virus may occur by excess or deficiency of metal ion [3]. Certainly, regulation of inherent biological processes in this manner could produce selective antiviral effects. In a survey with various metal ions, zinc was the only one capable of inhibition of viral replication [39]. The mechanism of action is believed to be interference with the processing of viral polypeptides by inhibition of proteolytic cleavage [6]. The zinc may bind to the polypeptide and prevent the approach of the proteolytic enzyme [40]. Copper and nickel salts, interestingly, also inhibit peptide hydrolysis [41]. Zinc ions may also act on viral DNA polymerases [42,... 

Oxidative cleavage of 280 by copper(ll) acetate generates a peroxy radical, which oxidizes the substrate to form an alcohol function and an oxy radical. Further reaction with the substrate affords again the corresponding alcohol in addition to a carbon radical. Thus, two equivalents of alcohol and only one equivalent of the carbon radical are formed. Since the reaction products originate from the carbon radical (see Fig. 112), the maximum yield could be 33%. The combined yields of 274 on one hand and 275-279 on the other hand are actually higher, hence further reduction of the alcohol must have occurred. It is very iikely that the copper(l) ion, which behaves as a moderately strong reductant (99), converts the alcohol, at least partially, to the reactive carbon radical. This mechanism explains the catalytic activity of copper(ll) acetate and resembles the reaction of arene diazonium compounds with copper(l) salts (100). 

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