Amide hydrolysis mononuclear

As with amide hydrolysis reactions, extensive mechanistic studies of metal-mediated phosphate monoester hydrolysis reactions have been performed using exchange inert mononuclear Co(III) complexes.9,188-202 To date, only a few zinc complexes that promote phosphate monoester hydrolysis have been reported. A binuclear zinc complex supported by a macrocyclic cryptate ligand (Fig. 36)... 

Nitrile Hydratase (see Iron Proteins with Mononuclear Active Sites). Nitrile hydratase catalyzes the hydrolysis of organic nitriles to the corresponding amide (see equation 2) and plays an important role in the assimilation of nitriles by microorganisms. 

Zinc enzymes catalyze the hydrolysis of amide bonds using a variety of active site structural motifs.77 An extensively studied enzyme of this class is carboxypeptidase A, which contains a mononuclear zinc center (Fig. 13) within the enzyme active site and catalyzes the hydrolysis of a C-terminal amino acid.78,79 The mechanism of amide cleavage in carboxypeptidase A has been studied extensively.77,78 In one proposed mechanistic pathway for this enzyme (Scheme 13), termed the zinc hydroxide mechanism , the zinc center activates a water molecule for deprotonation and also assists in polarization of the substrate carbonyl moiety, thus making it more susceptible to nucleophilic attack. The zinc center also provides transition state stabilization through charge neutralization. 

A mononuclear zinc hydroxide complex supported by a hydrophobic hydro-tris(pyrazolyl)borate ligand mediates the stoichiometric hydrolysis of an activated amide.94 As shown in Scheme 17, treatment of [(TpCum,Me)Zn-OH] with... 

Amide bonds are extremely stable and their half-life for hydrolysis in neutral aqueous solution is estimated to be seven years. " Zine(II)-OH speeies (derived from mononuclear Zn complexes) alone are incapable of hydrolyzing amide bonds. Rather, Zn -OH species may often act as a base to deprotonate amides. 

Metal-mediated reactions involving water are essential to life and catalytic industrial processes [1-3]. In biological systems, metalloenzymes containing various divalent metal ions catalyze the hydrolysis of amide, carboxylic ester and phosphate ester bonds using both mono- and multinuclear active-site structural motifs [4—6], Mononuclear metal centers are also found within the active sites of enzymes that catalyze the hydration, or the addition of water, to CO2 [Zn(II)] and nitriles [Co(III)/Fe(III)j [7-10]. In many of these processes, formation of a metal hydroxide moiety via deprotonation of a metal-coordinated water molecule is a key proposed step in the reaction pathway. Thus, a substantial amount of research over the past several years has been directed at dehneating how the structural and electronic environments of biological metal ions influence the pKa of a metal-bound water molecule. In this regard, studies directed at the preparation, characterization and elucidation of the reactivity of discrete metal aqua and hydroxo complexes have been paramoimt [11-13]. 

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