Metalloporphyrin model systems

This chapter will describe the detailed mechanisms of 02 activation by a main representative of each class of hemoproteins. Then, efforts to mimic oxygenases by using model systems based on metalloporphyrins will be reviewed. In fact, metalloporphyrin model systems have proved to be useful for three main objectives. The first is to determine the detailed structure of the iron complexes... 

This chapter has reviewed certain experimental results and computational studies involving some of the metalloporphyrins (Fe(II)P, Co(II), and others). The present investigation also explored the accuracy of several DFT methods. The geometries of MP-XO complexes and XO binding energy were found to depend very strongly on the functional and basis set used. In many cases, model systems should be described at least with a triple- quality basis set. 

Metalloporphyrins have been used for epoxidation and hydroxylation [5.53] and a phosphine-rhodium complex for isomerization and hydrogenation [5.54]. Cytochrome P-450 model systems are represented by a porphyrin-bridged cyclophane [5.55a], macrobicyclic transition metal cyclidenes [5.55b] or /3-cyclodextrin-linked porphyrin complexes [5.55c] that may bind substrates and perform oxygenation reactions on them. A cyclodextrin connected to a coenzyme B12 unit forms a potential enzyme-coenzyme mimic [5.56]. Recognition directed, specific DNA cleavage... 

Abstract. We report the results of experimental and theoretical studies of 13C and 15N shifts in proteins and model systems, together with 57Fe shifts and Mossbauer quadrupole splittings (electric field gradients) in metalloporphyrins and metalloproteins. The ability to relate these spectroscopic observables to structure by using quantum chemical methods opens up new opportunities for predicting and refining protein structure. 

This leads us finally to a brief discussion of our recent work on metalloproteins, and their model systems, metalloporphyrins. Here, the basic longterm objectives are to obtain a better understanding of how CO and 02, and their isoelectronic counterparts the isocyanides (RNC) and nitrosoalkanes/nitrosoarenes (RNO), bind to Fe, as well as to probe the structure of cytochrome c, a small protein involved not only in electron-transfer, but in apoptosis, or programmed cell death (44). 

Figure 12 Examples of metalloporphyrins used in model systems of cytochrome P-450. TPP, fMeso-tetraphenyIporphyri n TDCPP, /wesotetrakis-(2,6-dichlorophenyl) porphyrin TDCPCl8P, /weiotetrakis-(2,6-dichlorophenyl)-P-octachloroporphyrin.

The observation that cytochrome P 450 can be driven by hydroperoxides and related oxygen donors suggests that metalloporphyrins can be made to function as oxygen-transfer catalysts in simple model systems. 

The second example of research being funded by DOE involves a model system, metalloporphyrin, which looks at excited-state evolution using time-resolved X-rays. This research sets the groundwork for future research that will be conducted on much shorter time scales than the femtosecond domain. 

The use of a synthetic model system has provided valuable mechanistic insights into the molecular catalytic mechanism of P-450. Groves et al. [34]. were the first to report cytochrome P-450-type activity in a model system comprising iron meso-tetraphenylporphyrin chloride [(TPP)FeCl] and iodosylbenzene (PhIO) as an oxidant which can oxidize the Fe porphyrin directly to [(TPP)Fe =0] + in a shunt pathway. Thus, (TPP)FeCl and other metalloporphyrins can catalyze the monooxygenation of a variety of substrates by PhIO [35-40], hypochlorite salts [41, 42], p-cyano-A, A -dimethylanihne A -oxide [43-46], percarboxylic acids [47-50] and hydroperoxides [51, 52]. Catalytic activity was, however, rapidly reduced because of the destruction of the metalloporphyrin during the catalytic cycle [34-52]. When (TPP)FeCl was immobilized on the surface of silica or silica-alumina, catalytic reactivity and catalytic lifetime both increased significantly [53]. There have been several reports of supported catalysts based on such metalloporphyrins adsorbed or covalently bound to polymers [54-56]. Catalyst lifetime was also significantly improved by use of iron porphyrins such as mew-tetramesitylporphyrin chloride [(TMP)FeCl] and iron mcA o-tetrakis(2,3,4,5,6-pentafluorophenyl)por-phyrin chloride [(TPFPP)FeCl], which resist oxidative destruction, because of steric and electronic effects and thereby act as efficient catalysts of P-450 type reactions [57-65]. 

Substituents in the porphyrin ring systems may confer stability and selectivity toward oxidation these attributes are fundamental to the development of efficient model systems mimicking hemoprotein activities. Metalloporphyrins are very vulnerable to destructive oxidation of the porphyrin ligand under strongly oxidizing conditions. Thus, Groves et al. 

The mechanism of oxygen activation by P-450 has been extensively studied (7c, 5a, b) however, cmcial intermediates in the catalytic cycle are so unstable that it is not possible to examine their structures and reactivities. Accordingly, model systems for P-450 with synthetic metalloporphyrins have illuminated the enzymic reaction mechanism. For instance, the so-called picket fence porphyrin, /ncjo-tetra(a,a,a,a-pivalamidophenyl)porphyrin (TpivPP) Fe(II), prepared by Collman and co-workers, forms a stable complex with O2 6a, b). An X-ray... 

In this review, we will focus on the mechanistic aspects of the oxygen activation and reactions of the P-450 systems involving metalloporphyrins. For this purpose, we will briefly outline some of the chemistry of P-450 and examine in detail the mechanisms of oxygen transfer by comparing the enzymic system to the model studies. At this time, applications of these model systems in synthetic chemistry have not been extensively pursued. 

Another approach to the simulation of the catalyst s microenvironment is its immobilization on a solid support, i.e., the formation of heterogeneous oxygenase systems. Immobilization of a metalloporphyrin on porous glass [80] or polyvinylpyrrolidone [81] markedly increases the selectivity of alcohol formation. Immobilization of an iron-porphyrin complex on zeolites [82], Si02 [83] and especially on graphite, strongly increases the steric effects, which are observed in hexane oxidation in model systems with active oxygen species [84]. The effect of the matrix is not confined to the increase in the steric hindrances around the active oxidant. It can also be accompanied by a sieve effect, which is well-known for zeolites and accounts for the differences in the substrate specificity. 

This survey is limited to model systems based on synthetic water-soluble metalloporphyrins. The activity of KHSOs/sulfonated metalloporphyrin models has been checked with the usual... 

Summary of System Mode Frequencies (Harmonic and Corrected Anharmonic), VER Time Constants, and the Assignments Derived from Calculations at B3LYP/6-31G(d) Level for the Metalloporphyrin Models for Use in the Time-Dependent Perturbation Theory... 

Photoinduced electron transfer reactions in supramolecular model systems based on metalloporphyrins 97YGK557. 

Synthetic metalloporphyrins have received a lot of recent attention as mimics of numerous enzymes. In addition, 10 models have been developed for peroxidases and particularly, ligninases. Metalloporphyrins have also found utility as model systems for studies of the oxidative metabolism of drugs.A detailed study of the metabolism of lidocaine has been reported, as have preliminary studies on the use of metalloporphyrins as chemical mimics of cytochrome P450 systems (Scheme 29.24). ... 

Many chemical model systems based on metalloporphyrin catalysts and mimicking cytochrome P450-dependent monooxygenases have been described during these last decade. Several review articles have been devoted to these systems 2-10. in that context, very recent results about the preparation and catalytic properties of new homogeneous and supported catalysts will be described in a first chapter. In the second chapter, some preliminary results showing that the oxidation of alkanes by a dioxygenase-like mechanism could occur in the presence of iron porphyrin catalysts activated either photochemically or thermally, will be reported. 

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