Studies On Mimicry Of Hydrolytic Metalloenzyme

The mimicry of hydrolytic metalloenzyme is one of frontiers in chemistry and bionics. Using metal complexes and metallomicelle as biomimetic models for hydrolytic metalloenzyme, the kinetics and mechanism for the hydrolysis of p-nitrophenyl picolinate (PNPP), p-nitrophenyl acetate (PNPA), bis(p-nitrophenyl)phosphate (BNPP) have been studied systematically in this dissertation, which provide useful information for elucidation of the mechanism by which hydrolytic metalloenzyme may operate and consequently provide a theoretical basis for designing highly effective artificial hydrolytic metalloenzyme.In order to elucidate the effects of different metal ions on hydrolysis of esters, a 14-membered tetra-aza-macrocyclic Schiff base ligand and its Cu(II), Zn(II) and Co(II) complexes have been synthesized. The kinetics and mechanism for the hydrolysis of carboxylic esters catalyzed by the complexes in nonionic surfactant Brij 35 micellar solution have been investigated systematically. The results indicate that the properties of the metal ion in complex have multiple effects on the hydrolysis of carboxylic ester. Therefore, the selection of metal ion in designing artificial hydrolytic metalloenzyme is especially important.For the purpose of studying the influence of the geometry of metal ion coordination on the hydrolysis of the carboxylic ester, the Cu(II) complex of a 18-membered tetra-aza-macrocyclic Schiff base ligand has been synthesized by template method. The catalytic hydrolysis of PNPP by this complex and by one with similar ligand has been investigated comparatively. The kinetic results show that the copper complexwith similar structure to the active site of a natural hydrolytic metalloenzyme exhibits much more higher activity than that with different structure from the active site of the natural hydrolytic metalloenzyme. This suggests that in constructing the model for hydrolytic metalloenzyme, much attention should be paid to the geometry of metal ion coordination besides the properties of metal ion itself.The dinuclear copper complex of bis(dioxocyclam) has been synthesized and investigated kinetically for the hydrolysis of PNPP to understand the synergistic effect of the two metal ions in hydrolytic metalloenzymes containing two or more metal center in their active sites. The study indicates that a "bifunctional catalytic mechanism" may be involved in the hydrolysis of PNPP catalyzed by the dinuclear copper complex. Two copper ions acting as double Lewis acid function synergistically in the hydrolysis of PNPP: one can bind and activate the substrate and the other activates water molecule as a nucleophile, which leads to the dinuclear copper complex possesses a much more higher catalytic activity than the corresponding mononuclear complex does.Three complexes of small molecular ligands bearing hydroxyl or carboxyl groups have been synthesized and their esterolytic activities towards PNPP in the presence of a nonionic surfactant Brij35 micelle have been studied to examine the functions of different functional groups. The experimental results show that the copper complex of the ligand bearing alcoholic hydroxyl groups is much more effective than that bearing carboxyl groups, which may result from the difference in nucleophilicity between two kinds of functional groups in addition to the structural difference of three complexes. Accordingly, the implementation of an artificial hydrolytic metalloenzyme must take into account the effectiveness of the nuleophile as well as the structural characteristics required for optimum catalysis.In order to develop an effective artificial nuclease, the hydrolysis of BNPP catalyzed by La(III) in the presence of two arhinoalcoholic ligands has been discussed. The kinetic results indicate that in the presence of aminoalcoholic ligands, La(III) is a very effective catalyst for PNPP hydrolysis. The catalytically active species may be the dinuclear lanthanum species. The mechanism may involve thesynergism of double Lewis acid activation of the substrate...