Zinc bound alkoxide

Insight into the role of the serine nucleophile in the catalytic cycle of alkaline phosphatase was gained through studies of the bis(4-nitrophenyl) phosphate reactivity of a mononuclear Zn(II) complex supported by the (S)-1 -(2-hydroxy-2-phe-nylethyl)- 1,4,7,10-tetrazacyclodecane ligand (Scheme 33).226 In aqueous solution, this complex exhibits a pKa value for the zinc-bound alkoxide moiety of 7.30 + 0.02. 

Inclusion of an alcohol appendage in the L24 ligand framework (Fig. 52) results in a reaction pathway for bis(4-nitrophenyl) phosphate hydrolysis that involves initial nucleophilic attack of a zinc-bound alkoxide moiety on the substrate to give a phosphorylated intermediate (Scheme 34).239 This intermediate, similar to the phosphorylated serine intermediate proposed in the catalytic cycle of alkaline phosphatase, is subsequently attacked by a Zn-OH moiety to yield 4-nitrophenyl... 

Ito and co-workers observed the formation of zinc bound alkyl carbonates on reaction of carbon dioxide with tetraaza macrocycle zinc complexes in alcohol solvents.456 This reversible reaction was studied by NMR and IR, and proceeds by initial attack of a metal-bound alkoxide species. The metal-bound alkyl carbonate species can be converted into dialkyl carbonate. Spectroscopic studies suggested that some complexes showed monodentate alkyl carbonates, and varying the macrocycle gave a bidentate or bridging carbonate. Darensbourg isolated arylcarbonate compounds from zinc alkoxides as a by-product from work on polycarbonate formation catalysis.343... 

The essential features of the catalytic cycle are summarized in Figure 12.6. After binding of NAD+ the water molecule is displaced from the zinc atom by the incoming alcohol substrate. Deprotonation of the coordinated alcohol yields a zinc alkoxide intermediate, which then undergoes hydride transfer to NAD+ to give the zinc-bound aldehyde and NADH. A water molecule then displaces the aldehyde to regenerate the original catalytic zinc centre, and finally NADH is released to complete the catalytic cycle. 

The essential features of the catalytic cycle (see Figure 10) involve the binding of NAD, the displacement of the water molecule by alcohol, the deprotonation of the coordinated alcohol to give a zinc alkoxide intermediate, the hydride transfer from the alkoxide to NAD to give a zinc-bound aldehyde, the displacement of the aldehyde by water and the release of NADH. The principal role of the zinc in the dehydrogenation reaction is, therefore, to promote deprotonation of the alcohol and thereby enhance hydride transfer... 

As early as 1972, Sigman and Jorgensen used a ternary zinc(II) complex of iV-(2-hydroxyethyl)ethylenediamine 4 and 4-nitrophenyl pi-colinate 5 as a model for Znn-alkoxide-promoted transesterification (see Scheme 1) (16). Although the Znn-bound alkoxide (its pKa kinetically determined to be 8.4) was shown to be a possible reactive species to give 6, the subsequent hydrolysis for completion of the ester hydrolysis as well as the catalytic cycle failed. 

A comparison of NA hydrolysis by 8 and 9 shows for the first time that Znu-bound alkoxides may lead to better nucleophiles than Zn11-bound hydroxides in an aqueous environment. Unless the alkoxide anion is bound to zinc(II) ion, it may rather work as a general base to yield hydroxide, which then yields the active nucleophile. Hence, zinc(II) ion may be viewed as an alkoxide-protecting agent. It is of... 

It is of interest that the ZnU bound thiophenolate attacks at a methyl carbon atom as electrophilic site, while the Znn-bound alkoxides, as described in Section II, attack at the P atom. In 32, zinc(II) assembles and protects (from oxidation) the four strong nucleophiles CeH5S. While alcohols and water (pKa both ca. 15) need zinc(II) to be activated at physiological pH, thiophenol (pKa ca. 7) may not require zinc(II) for activation. 

Tagaki et al. [24] and Fomasier et al. [25] reported another type of metallomicelle attached with a metal-bound alkoxide nucleophile. Tagaki s zinc(II) and copper(II) complexes (with possible structures 6a and b) promoted the hydrolysis of 4-nitrophenyl picolinate in a comicellar system with hexadecyl trimethy-lammonium bromide. However, no detailed mechanistic study was reported. Scrimin s zinc(II) and copper(II) complexes (proposed structures 7a and b) also promoted the hydrolysis of 4-nitrophenyl picolinate. A postulated mechanism for the catalytic activity of 7 is shown in Figure 4. An aggregate of 7 more effectively... 

In the presence of excess diisopropylzinc, the EXSY spectrum in both thf and toluene shows rapid interconversion between zinc-bound isopropyl groups of the zinc reagent and alkoxide dimer (Fig. 15). The reaction occurs for both racemic and homochiral dimers with comparable facility. In toluene, the rate... 

Kimura and co-workers have synthesized a series of alkoxide complexes with the alcohol functionality as a pendent arm.447 674 737 A zinc complex of l-(4-bromophenacyl)-l, 4,7,10-tetraaza-cyclododecane was also synthesized by the same workers to mimic the active site of class II aldolases. The X-ray structure shows a six-coordinate zinc center with five donors from the ligand and a water molecule bound. The ketone is bound with a Zn—O distance of 2.159(3) A (Figure 12). Potentiometric titration indicated formation of a mixture of the hydroxide and the enolate. Enolate formation was also independently carried out by reaction with sodium methoxide, allowing full characterization.738... 

Some model Zn2+ complexes of the ethanol-pendant [12]aneN3 (34i) and ethanol-pendant cyclen (228) were reported. The former formed a dimeric alkoxide complex, while the latter (pifa 7.6) yielded a mononuclear hydroxide species. Some model Zn2+ complexes of carboxy-methyl and carboxyethyl and carboxypropyl pendant cyclen were prepared. All these zinc complexes exist in equilibrium between the CO2-bound and CO2 -unbound forms in acidic aqueous solution. Herr et al. (229) synthesized some zinc(II) complexes with tripodal peptide ligands with histidine side chains to mimic the zinc(II)-coordination sphere of CA. 

The potentiometric pH titration disclosed monodeprotonation with a pK value of 7.6 at 25°C. On the basis of NMR spectroscopic and anionbinding studies of 13, the monodeprotonated species was assigned to the OH -bound ZnL complex 14, rather than the pendent alkoxide complex as seen with [12]aneN3 8b. Nevertheless, among all past zinc(II) complexes, 14 seems to be the most active catalyst for NA hydrolysis. From kinetic studies in 10% (v/v) CH3CN at 25°C and pH... 

In 1999, Nozaki and co-workers were the first to report an asymmetric copolymerization, catalysed by a chiral amino-alkoxide zinc complex 15 (Table 6) and producing optically active PCHC with 70% ee (measured by hydrolysing the copolymer and analysing the resulting diol using chiral GC) [138,148], The crystal structure of the catalyst, reported subsequently, showed a dimeric structure it was unclear whether the dimer was maintained during the copolymerization [148], In the solid state, the zinc-zinc distance in the catalyst was determined to be 3.00 A (vs. ca. 4 A, for the loosely bound BDI zinc dimers). 

Structure. The presence of an oxygen atom directly bound to zinc increases both the electron deficiency of the zinc and the donor character of the oxygen atom. This condition will inevitably result in intermolecular (see Intermolecular) association increasing the coordinative saturation of zinc and leading to high thermal stability and low sensitivity towards oxygen and moisture. Organozinc alkoxides and aryloxides... 

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