8.11.3.1 Models of Horseradish Peroxidase
Early peroxidase models were based on simple metal complexes or modified hemin derivatives.155 Anionic metalloporphyrins adsorbed on ion-exchange resins have an efficient peroxidase activity,
which has been monitored by titration of the quinoid dye generated in the co-oxidation of 4-aminoantipyrine and phenol in the presence of hydrogen peroxide.156 Oxidation of phenols and tertiary amines has been performed with different metalloporphyrins and various oxidants (not only hydrogen peroxide, but also alkylhydroperoxides, organic peracids, or aromatic amine N-oxides).157–159All these different metalloporphyrin complexes exhibit catalytic activities similar to those of peroxidases: oxidation of phenols, N-dealkylation of tertiary amines. Iron(III) or manganese(III) complexes of meso-tetrakis(2,6-dimethyl-3-sulfonatophenyl)porphyrin or meso- tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin are suitable water-soluble peroxidase models, since these metalloporphyrins do not form -oxo dimers, neither do they aggregate due to steric hindrance created by theortho substituents.
Microperoxidases-8 or -11 (MP-8 or MP-11) have been used as peroxidase models. These com- pounds consist of a peptide fragment (8 or 11 residues) containing a covalently bound heme, and are obtained by the enzymatic hydrolysis of cytochromec.160–162MP-8 and -11 are able to catalyze the N-demethylation of amines and the oxidation of sulfides, in the same manner as peroxidases.
Artificial peroxidases have also been designed using the catalytic antibody strategy. The groups of Schultz and Harada initiated the field of antibody–metalloporphyrin complexes.163,164Immuniza- tion with meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) provides an antibody which binds very strongly to MnIII-TCPP or to FeIIITCPP.165
Peroxidase models based on metalloporphyrins have been used for thein vitrooxidation of drugs or drug candidates, since these biomimetic methods can be considered as a promising complemen- tary approach to traditional techniques used to carry out oxidative activation of drugs (perfused organs, isolated cells, tissue homogenates, or purified enzymes). These biomimetic catalysts should facilitate the preparation and the isolation of reactive metabolites, due to the absence of proteins in the reaction mixture (electrophilic metabolites are usually trapped by nucleophilic sites of proteins).
Several groups have developed the use of these metalloporphyrins in organic or aqueous solutions to catalyze the oxidation of drugs such as acetaminophen,166 piperidine derivatives,167 ellipticine derivatives,168lidocaine,169and an antagonist of a vasopressin receptor.170When using sterically hindered metalloporphyrins and monopersulfate as primary oxidant, the catalytic activities of these peroxidase-type oxidations are very close to that observed with horseradish peroxidase.168
The horseradish-catalyzed oxidation of luminol is widely used in the field of nonradioactive immunology assays. Iron and manganese porphyrins are also highly efficient catalysts when using perborate as oxidant. The chemiluminescence produced by nanomolar concentrations of Fe–
TPPS can be over three times as strong as that produced by HRP, with a signal-to-noise ratio increasing up to 200.171
8.11.3.2 Models of Chloroperoxidase
Only a few reports have been devoted to the modeling of chloroperoxidase with metalloporphyrin catalysts. In the absence of protein around the active site to control the electron transfer, the oxidation of chloride ions competes with the direct oxidation of organic substrates by the high- valent metal–oxo species. The first CPO model was based on the association of NaClO2with an iron porphyrin, generating HOCl in situwhich reproduced the main features of CPO-catalyzed chlorinations.172 A second CPO model, using hydrogen peroxide and chloride ions, has been developed with an anionic manganese porphyrin supported on a cationic ion-exchange resin (the structures of these supported catalysts will be discussed in the next paragraph on ligninase models).173MnTMPS supported on a polyvinylpyridine polymer (PVP) was able to catalyze the oxidation of dimedone, a classical CPO substrate, to chlorodimedone.
A synthetic iron porphyrin with a thiolato ligand in the axial position has been oxidized by hydrogen peroxide in the presence of chloride. The shift of the Soret band from 408 nm to 404 nm might be due to the formation of a putative FeIIIOCl entity which can generate free HOCl after protonation.174The kinetic parameters of halide oxidation by a high-valent manganese–oxo porphyrin complex have been reported.175
8.11.3.3 Models of Ligninase
This survey is limited to model systems based on synthetic water-soluble metalloporphyrins.176–179 The activity of ‘‘KHSO5/sulfonated metalloporphyrin’’ models has been checked with the usual
lignin-model molecules: veratryl alcohol and 1-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy) propane-1,3-diol. Sterically hindered, water-soluble complexes are among the most efficient metalloporphyrin catalysts. The degradation products of lignin models are similar to those obtained in ligninase-catalyzed oxidations.180,181
Iron(III) meso-tetrakis(pentafluorophenyl)--tetrasulfonatoporphyrin is also an efficient cata- lyst for the oxidation of lignin models with hydrogen peroxide or magnesium monoperphthalate.182 Sulfonated metalloporphyrins are also efficient catalysts in ligninase modeling when they are supported on ion-exchange resins. For example, FeTPPS or MnTPPS strongly interacts with the cationic Amberlite IRA 900 (an ion-exchange resin derived from polyvinylbenzene and bearing ammonium residues) to give solid-supported catalysts that are more stable than the corresponding soluble catalysts.178With a polyvinylpyridine (PVP) support, it has been possible to take advan- tage of the proximal effect of a pyridine ligand without free pyridine present in the reaction mixture.183,184
Ligninase models have been evaluated as catalysts for pollutant oxidation. Sulfonated iron or manganese porphyrin catalysts with KHSO5or H2O2as primary oxidant were able to effectively promote the oxidative dechlorination of 2,4,6-trichlorophenol (TCP) to 2,6-dichlorobenzoqui- none. Catalytic activities of up to 20 cycles s1were observed with monopersulfate as oxidant and a very low loading of FeTPPS catalyst (0.1–0.3% molar ratio with substrate).185Changing this oxidant for hydrogen peroxide resulted in a decrease in the catalytic activity. However, the limits of this catalytic reaction are set by a lower catalytic activity with H2O2, the cost of metallopor- phyrins, and the absence of extensive oxidation of the generated quinones. Consequently, a biomimetic system able to degrade trichlorophenols should be based on a cheap and readily available catalyst with H2O2 as oxidant (the ‘‘clean’’ oxidant, water being the only by-product after oxidation); and, also, the oxidation of TCP should be able to generate ring-cleavage products and CO2, as in biomineralization processes. We found that iron(III) tetrasulfonato- phthalocyanine (FePcS) was able to catalyze the H2O2oxidation of TCP according to the reaction conditions listed above.186–188With 3.7% of FePcS and five equivalents of H2O2with respect to 2,4,6-trichlorophenol in a mixture of acetonitrile/buffered water (1/3, v/v) at pH 7, TCP was quantitatively converted at room temperature within a few minutes (TCP concentra- tionẳ2,000 ppm). The major TCP cleavage product was chloromaleic acid (yieldẳ24%) with chlorofumaric, maleic, and fumaric acids as minor products. Oxalic acid was also among the oxidation products of TCP.188The C4-diacids resulting from the ring cleavage of TCP by FePcS/
H2O2were also degraded by the catalytic system. The possible formation of carbon dioxide as the ultimate degradation product of these diacids was investigated by monitoring the release of labeled CO2during the oxidation of a (U-14C)-TCP by FePcS/H2O2in order to have a complete material balance of oxidation products.187After 90 min at room temperature, 11% of the initial radioactivity was recovered as CO2.
Polyaromatics (anthracene and phenanthrene) have also been oxidized by FePcS/H2O2.189 This catalytic system is highly influenced by the presence of an organic co-solvent and phosphate ions.190,191Iron tetra-amide complexes are also able to efficiently catalyze the oxidative cleavage of TCP with hydrogen peroxide at basic pH values.192
8.11.3.4 Models of Manganese Peroxidase
The modeling of a nonspecific peroxidase like ligninase is relatively simple compared to the design of metalloporphyrin catalysts able to selectively oxidize manganese(II) salts, in the presence of chelating agents and of easily oxidizable phenolic substrates. MnP has a manganese binding site able to control the selective oxidation of manganese(II) salts in the presence of phenols. Oxidation of MnIIpyrophosphate to the corresponding MnIIIchelate was performed with catalytic amounts of iron- or manganese-sulfonated porphyrins.193 As expected, sterically hindered iron complexes were the most active catalysts (8 cycles min1and 3 cycles min1for FeTDCPPS and FeTMPS, respectively). A striking feature of this metalloporphyrin-catalyzed oxidation of manganese pyrophosphate was the enhancement of the catalytic activity by the addition of limited amounts of methoxylated benzene derivatives acting as co-substrates: 1,2-dimethoxybenzene, 3,4-dimethoxy- benzyl alcohol (veratryl alcohol), or 1,2,4-trimethoxybenzene. The catalytic activity of FeTMPS was strongly increased by 2–5% of one of these methoxylated benzenes. In order to mimic the manganese binding site of MnP, a metalloporphyrin bearing a manganese chelating ligand has been prepared.194