Biomimic

In 1999, Yamamoto reported the first example of an enantioselective biomime tic polyene cychzation using chiral LBAs as artificial cyclases. The LBA cyclase is believed to participate in the initial enantioselective protonation of the terminal isoprenyl group which induces concomitant diastereoselective cychzation [128]. Subsequent work by the Yamamoto group led to the development of LBA 52 as an artificial cyclase for hydroxypolyprenoids (Scheme 5.68) [129]. LBA 52 mediated cychzation of the the appropriate achiral hydroxypolypreniods permitting the short total syntheses of (-)-Chromazonarol, (-i-)-8-epi-puupehedione, and (-)-ll -deox-ytaondiol (not shown). 

Biomimics of noncatalytic, or structural, zinc generally focus on zinc-thiolate clusters designed after the metal—thiolate clusters of metal-lothionein (see Section IV,C). Adamantoid anions of formula [ (jiz-SPh)6(ZnSPh)4] are targets of synthetic and structural study, where each metal ion is coordinated in tetrahedral fashion by bridging and terminal thiolate ligands (see Hencher et al., 1985 Dean and Vittal, 1987, and references cited therein). 

Fig. 2. The zinc-bound water molecule of this rigid metalloamide complex exhibits a pKa of about 7 (Groves and Olson, 1985). The complex is a biomimic of the tetracoordinate metal ion in the carboxypeptidase A active site.

Tan YG, Peng H, Liang CD, Yao SZ. A new assay system for phenacetin using biomimic bulk acoustic wave sensor with a molecularly imprinted polymer coating. Sens AcUiat B 2001 73 179-184. 

M Knite, Teteris V, Kiploka A, (2003) Mater Sci Eng C Biomim Supramol Syst C23 787... 

Clague MJ, Keder NL, Butler A (1993) Biomimics of Vanadium Bromoperoxidase Vanadium(V)-Schiff Base Catalyzed Oxidation of Bromide by Hydrogen Peroxide. Inorg Chem 32 4754... 

Undoubtedly, mimetic models of enzymes must conform to definite physicochemical features of the target enzyme. The specific feature of any biomimic is its relatively small size and simpler structure. 

It is the author s opinion [3] that this means of creating miniature enzymes is accessible to chemists, who are experts in synthesis. In this case, the mandatory requirement is the following active catalytic groups of the biomimic must be oriented to conform to the geometry of the active site of the enzyme consisting of catalytic groups. 

It is naturally concluded [7] that, finally, all the information obtained with the help of the model must be compared with the behavior of the enzymatic system studied in vivo in order to achieve bioorganic models of systems existing in the nature. The difficulty of such an approach to the design of highly effective biomimics—the catalysts of chemical reactions— will be justified below. 

In heterogeneous inorganic biomimics objectives (2)—(4) are resolved more easily than for organic mimics. Many acidic and basic sites on an inorganic carrier (matrix) form a situation in the biomimetic system when a definite quantity of these sites will display the required geometry for substrate-activated complex formation. 

This condition is met in the case of heterogeneous inorganic biomimics—the surface on which the adsorbed active site has a rigid structure, and catalytic activity of the surface always depends on the site catalytic domain correspondence to the substrate structure and orientation. 

Thus, if it is taken into consideration that the overwhelming majority of enzymes is adsorbed on cell membranes and sensationally execute the functions under these conditions, this situation is of importance for enzymes (due to their sensitivity to the medium) rather than for their models, especially inorganic biomimics. 

Therefore, geometrical adequacy of the model and the substrate active sites will mean an increase in specificity. Of course, this reasoning is of the fundamental importance for the design of biomimics. 

The basic question of mimetic catalysis is the determination of physicochemical properties of enzymes to be simulated in the synthesized biomimic in accordance with the reaction modeled. Firstly, let us try to answer one of the key questions that arise in biomimic construction how important is it to reach the enzymatic specificity in the synthesis of their analogs To put it another way, should the dynamic (tertiary) structure of the enzyme responsible for the selectivity control mechanism be simulated by active site protection from competitive admixtures This feature of the enzymes distinguishes them from usual catalysts. 

Common catalytic systems are characterized by the presence of reagent molecules only, whereas the enzymatic system is multicomponent and possesses low concentrations of the substrates in water. The interaction between a substrate with an oxidant or a reducer is most often considered. This makes unnecessary simulation of the enzyme selectivity. However, free contact of reagent molecules with active sites preserves the possibility of various mechanism realizations which is the reason for decrease of the process selectivity. Apparently, a compromise should be found in resolving the question of selectivity in biomimics development in suggesting that, though complex gap mechanism is the effective method for distance and mutual orientation control of reactive groups in the enzyme, it may hardly be implemented in synthetic systems. 

In principle, more or less stable BRC structures can be obtained in heterogeneous biomimics, especially when adsorption and catalytic sites are combined, i.e. active sites perform both functions fixation and transformation of the substrate. To put it another way, the above enumerated restrictions typical of homogeneous catalysis are absent in heterogeneous mimic-substrate complexes, where acidic-basic sites are fixed in required points of the active site. 

BIOMIMETIC CATALYSTS (BIOMIMICS) FOR CATALASE, PEROXIDASE AND MONOOXYGENASE REACTIONS... 

For preparation of stable liquid biomimics [15], it should be noted that the substrate (S) must be much more sensitive to oxidation than the catalyst ... 

It should be noted that the mechanism of catalyst deactivation (7.2) is a particular case, because the immobilized biomimic is protected from this danger. 

Tests on synthesized biomimics indicated their high catalase activity (specifically for these applied on A1202) in H202 dissociation. It is the author s opinion that these studies gave essentially important results for explaining the Chance complex formation. It consists of bonding of Fe3+ ion in the sixth coordinate position in the biomimic to hydroxide anion. In this very form it manifests catalase activity. 

Aqueous alcohol iron protoporphyrin solutions with pH > 10 (14 in the limit), required for preventing their interaction with one another, are most frequently used in the synthesis and reactions with biomimics. On the contrary, H202 dissociation was implemented in the presence of 5,10,15,20-tetrakis-(2,6-dimethyl-3-sulfonatophenyl)porphynato-Fe3+ H20 [(P)Fe3+(H20)] in a pH range of between 1 and 12 [65], This porphyrin is easily soluble in water and does not form dimeric and polymeric associates. Of interest are transition states shown in Figure 7.2. It is the author s opinion that the mechanism with heterolytical O—O bond break is the most preferable. 

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