Phosphate esters, coordinated

Hydrolysis of peptides,84 amides,85 phosphate esters,86 sulfonate esters87 and acetals88 can also be metal catalyzed. The hydrolysis of a phosphate ester coordinated to cobalt(III) also occurs at an increased rate (Scheme 19).89 A rather similar reaction occurs in the amine exchange of coordinated dithiocarbamates (equation 21).90 The conversion of imidates to amidines has been mentioned previously and is a similar type of reaction (see Section 7.4.2.2.1). 

Figure 17-10 An alternate mechanism for substrate binding to the dinuclear metal center, in which the phosphate ester coordinates to both Fe and Fe ions. Subsequent nucleophilic attack ensues from a /i-hydroxo ligand.

H-Bonding and Phosphate Ester Coordination to a Metal Center... 

Fig. 8.17 Mononuclear zinc complexes used to evaluate the influence of H-bonding on phosphate ester coordination to a zinc cation [111].

Perhaps the most extensively studied catalytic reaction in acpreous solutions is the metal-ion catalysed hydrolysis of carboxylate esters, phosphate esters , phosphate diesters, amides and nittiles". Inspired by hydrolytic metalloenzymes, a multitude of different metal-ion complexes have been prepared and analysed with respect to their hydrolytic activity. Unfortunately, the exact mechanism by which these complexes operate is not completely clarified. The most important role of the catalyst is coordination of a hydroxide ion that is acting as a nucleophile. The extent of activation of tire substrate througji coordination to the Lewis-acidic metal centre is still unclear and probably varies from one substrate to another. For monodentate substrates this interaction is not very efficient. Only a few quantitative studies have been published. Chan et al. reported an equilibrium constant for coordination of the amide carbonyl group of... 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

Much effort has been placed in the synthesis of compounds possessing a chiral center at the phosphoms atom, particularly three- and four-coordinate compounds such as tertiary phosphines, phosphine oxides, phosphonates, phosphinates, and phosphate esters (11). Some enantiomers are known to exhibit a variety of biological activities and are therefore of interest Oas agricultural chemicals, pharmaceuticals (qv), etc. Homochiral bisphosphines are commonly used in catalytic asymmetric syntheses providing good enantioselectivities (see also Nucleic acids). Excellent reviews of low coordinate (coordination numbers 1 and 2) phosphoms compounds are available (12). 

Recently, highly branched macromolecular polyamidoamine dendrimers have been prepared with Co11 bound where the metal ions have additional exchangeable coordination sites.450 These macromolecules show a capacity for catalyzing the hydrolysis of phosphate esters, presumably via intermediate bound phosphoester species. 

Two dinuclear complexes, with five-coordinate zinc centers, derived from tris((2-pyridyl)-methyl) amine were synthesized and bridging phosphate or phosphate ester groups. The X-ray structure of the phosphate monoester complex shows a syn-anti bridging mode in contrast to alkaline phosphatase in which it is syn-syn 448 Fenton and co-workers have also studied other related dizinc species of compartmental ligands 449... 

The cobalt(III) ion has a small size-to-charge ratio and is therefore a strong Lewis acid which strongly activates coordinated phosphate ester... 

The higher coordinating ability and Lewis acidity of Zn(H) ion in addition to the low pK of the metal-bound water molecule and the appearance of this metal ion in native phosphatases inspired a number of research groups to develop Zn(II)-containing dinuclear artificial phosphatases. In contrast, very few model compounds have been published to mimic the activity of Fe(III) ion in dinuclear centers of phosphatase enzymes. Cu(II) or lanthanide ions are not relevant to natural systems but their chemical properties in certain cases allow extraordinarily high acceleration of phosphate-ester hydrolysis [as much as 108 for copper(II) or 1013 for lanthanide(III) ions]. 

Vanadium is beneficial and possibly essential for humans. It is certainly essential for a number of organisms. Vanadate (oxidation state V) and its derivatives are phosphate analogues, showing both ground state and transition state analogy (both structural and electronic) with phosphorus compounds. The analogy of five-coordinate vanadium compounds with the transition state of phosphate ester hydrolysis is well documented, and explains why so many vanadium compounds are potent inhibitors of phosphatases, ribonucleases and ATPases. 

The enzymatic reaction was postulated to involve the same intermediate, with some of the coordinate bonds of the metal also attached to ligands on the enzyme. It was also possible, in the nonenzymatic reaction, to substitute an organic acid, such as acetate (34) for the orthophosphate the reaction proceeded in like fashion to produce a phosphate ester ... 

Phosphate esters, particularly AMP, ADP and ATP, have vital biological functions and this fact has generated intense interest in their reaction mechanisms. Subtle stereochemical experiments, such as the use of isotopically chiral compounds, have been important and, since all biological phosphorylation reactions appear to involve metal ion catalysis, the stereochemistry of phosphate ion coordination has also been subject to much attention.229,230 Apart from its biological significance, this work has revealed some interesting contrasts with the stereochemistry of ligand systems in which saturated carbon units link the donor atoms. 

Cobalt-coordinated amide nucleophiles have also been observed to attack coordinated phosphate esters (equation 38),148 disulfides (Scheme 47)149 150 and nitriles (Scheme 48).151>152 Chelated amides can also be formed by intramolecular attack of cobalt hydroxides.153... 

The [(NH3)5CoOP(OMe)3]3+ ion has recently been shown292 to react with SCN, I or S2032-to produce (NH3)5Co02P(OMe)2]2+ and respectively MeSCN, Mel or MeS203. The reactions are believed to occur by SN2 substitution at carbon. This establishes a new mode of reaction for a coordinated phosphate ester. The rate enhancement on coordination is ca. 150. 

There have been a few reports of first generation coordination complex structural models for the phosphatase enzyme active sites (81,82), whereas there are some examples of ester hydrolysis reactions involving dinuclear metal complexes (83-85). Kim and Wycoff (74) as well as Beese and Steitz (80) have both published somewhat detailed discussions of two-metal ion mechanisms, in connection with enzymes involved in phosphate ester hydrolysis. Compared to fairly simple chemical model systems, the protein active site mechanistic situation is rather more complex, because side-chain residues near the active site are undoubtedly involved in the catalysis, i.e, via acid-base or hydrogenbonding interactions that either facilitate substrate binding, hydroxide nucleophilic attack, or stabilization of transition state(s). Nevertheless, a simple and very likely role of the Lewis-acidic metal ion center is to... 

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