Carbonic anhydrase model

The interaction of carbon disulfide as a substrate in carbonic anhydrase model systems has been studied using density functional theory methods. A higher activation energy of CS2 compared to C02 in the reaction with [L3ZnOH]+ was due to the reduced electrophilicity of CS2. The reversibility of the reaction on the basis of these calculations is questionable with [L3ZnSC(0)SH]+ as intermediate.572... 

The study of zinc-aqua complexes as synthetic carbonic anhydrase models has shown a low coordination number and a hydrophobic environment to be prerequisites for a low pK value of the aqua ligand, which is essential for efficient enzyme function. The pK value in the case of 13 is expected to be greater than 10.7, which is the value determined for pentacoordinate [Zn(tren)(H20)](C104)2, in which the water ligand is more strongly bound and thus expected to be more acidic (cf. the discussion of bond lengths, above). Thus, 13 is not expected to show carbonic anhydrase-like reactivity. However, in related tetraazamacrocyclic systems it has been shown that upon... 

Tpx have been employed as ligands in carbonic anhydrase models (Fig. 8.10). 

Biological Models and Their Characteristics, p. 101 Carbonic Anhydrase Models p. 178 Enzyme Mimics, p. 546... 

CARBONIC ANHYDRASE MODELS WITH MACROCYCLIC TRIAMINES... 

Artificial Enzymes, p. 76 Carbonic Anhydrase Models, p. 178 Catalytic Antibodies, p. 193 Cyclodextrins, p. 398... 

Carbohydrates, Recognition of, p. 169 Carbonic Anhydrase Models, p. 178 Carcerands and Hernicarcerands. p. 189 Cation-n Interactions, p. 214 Cavitands, p. 219 Chiral Guest Recognition, p. 236 Classical Descriptions of Inclusion Compounds, p. 253 Classification and Nomenclature of Supramolecular Compounds, p. 261 Clathrate Hydrates, p. 274 Conzplexation of Fullerenes, p. 302 Concepts in Ciystal Engineering, p. 319 Crown Ethers, p. 326 Cryptands, p. 334 Cryptophanes, p. 340 Cyclodextrins, p. 398... 

Carbonic Anhydrase Models, p. 178 Carcerands and Hemicarcerands, p. 189 Cation-n Interactions, p. 214 Cavitands. p. 219... 

The coordination numbers as well as the geometry of the model complex correspond to the active center of carbonic anhydrase. The of 7.3 of the Zn " "-bound water is similar to that of the natural enzyme. With these characteristics, the Zn +-[12]aneN3-complex 1 is one of the best carbonic anhydrase models known so far and superior to other closely related macrocyclic polyamine complexes. For example, the analogous Cu -complex 2 or the similar Zn +-[12]aneN4-complex 3 shows a lower catalytic activity, mainly caused by the higher pA a values of the bound water. ... 

Macrocyclic polyamine Zn +-complexes not only were used as carbonic anhydrase models. They were also shown to promote hydrolytic cleavage of phosphate esters and in particular phosphate diesters as present in DNA. In Figure 3, the catalytic cycle for monometallic activation is shown. Dissociation of a metal-bound water molecule provides a metal hydroxide species, which nucleophilically attacks the phosphorus center of a phosphate diester, whereby finally the aUcoxide gets released and the product is formed. 

On treatment with potassium iodide, the capped disulfonate j8-cyclo-dextrin discussed above could easily be converted to the corresponding diiodide jS-cyclodextrin. With appropriate nucleophiles (imidazole, histamine) a new route to bis(iV-imidazolyl)-j8-cyclodextrin and bis(iV-histamino)-j8-cyclodextrin was developed by Tabushi s team (182). In the presence of Zn(II) ion, both regiospecifically bifunctionalized cyclodextrins hydrate CO2 and are the first successful carbonic anhydrase models. The Zn(II) ion binds to the imidazole rings located in the edge of the cyclodextrin pocket and the presence of an additional basic group, as with bis(histamino)-cyclodextrin-Zn(II), enhances the activity. Therefore, the present models show that all three factors, Zn(II)-imidazole, hydrophobic environment, and a base seem to help to generate the carbonic anhydrase activity (182). The chemistry of this enzyme is further discussed in Section 6.2, p. 331. 

I. Tabushi, Y. Kuroda, and A. Mochizuki (1980), The first successful carbonic anhydrase model prepared through a new route to regiospecifically bifunction-alized cyclodextrin. /. Amer. Chem. Soc. 102, 1152-1153. 

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