Metalloporphyrins activity

There have been a number of studies of the important class of proteins that have metalloporphyrin active sites. Models for the metalloporphyrin and corphinoid sites have been derived by modeling small molecules and extending the AMBER 451 and lMiu [6. 196,398] slightly modified version of the AMBER force field... 

The above-described structures are the main representatives of the family of nitrogen ligands, which cover a wide spectrum of activity and efficiency for catalytic C - C bond formations. To a lesser extent, amines or imines, associated with copper salts, and metalloporphyrins led to good catalysts for cyclo-propanation. Interestingly, sulfinylimine ligands, with the chirality provided solely by the sulfoxide moieties, have been also used as copper-chelates for the asymmetric Diels-Alder reaction. Amide derivatives (or pyridylamides) also proved their efficiency for the Tsuji-Trost reaction. 

The simple porphyrin category includes macrocycles that are accessible synthetically in one or few steps and are often available commercially. In such metallopor-phyrins, one or both axial coordinahon sites of the metal are occupied by ligands whose identity is often unknown and cannot be controlled, which complicates mechanistic interpretation of the electrocatalytic results. Metal complexes of simple porphyrins and porphyrinoids (phthalocyanines, corroles, etc.) have been studied extensively as electrocatalysts for the ORR since the inihal report by Jasinsky on catalysis of O2 reduction in 25% KOH by Co phthalocyanine [Jasinsky, 1964]. Complexes of all hrst-row transition metals and many from the second and third rows have been examined for ORR catalysis. Of aU simple metalloporphyrins, Ir(OEP) (OEP = octaethylporphyrin Fig. 18.9) appears to be the best catalyst, but it has been little studied and its catalytic behavior appears to be quite distinct from that other metaUoporphyrins [CoUman et al., 1994]. Among the first-row transition metals, Fe and Co porphyrins appear to be most active, followed by Mn [Deronzier and Moutet, 2003] and Cr. Because of the importance of hemes in aerobic metabolism, the mechanism of ORR catalysis by Fe porphyrins is probably understood best among all metalloporphyrin catalysts. 

As a result of strong electronic interactions between the two metalloporphyrin units, there is a substantial uncertainty in assigning oxidation states in mixed-valence group 2 complexes of redox-active metals, such as Co. Thus, although reduced neutral C02 derivatives can be reasonably well described as those of Co the location (metal versus porphyrin) of the electron hole(s) in the singly and doubly oxidized derivatives is not known definitively, and may be very sensitive to the medium [LeMest et al., 1996, 1997]. For example, in benzonitrile, the UV-vis spectmm of [(FTF4)Co2]" ... 

So far, certain biomimetic catalysts (1 and 2b in Fig. 18.17) have been shown to reduce O2 to H2O under a slow electron flux at physiologically relevant conditions (pH 7,0.2-0.05 V potential vs. NHE) and retain their catalytic activity for >10" turnovers. Probably, only the increased stability of the turning-over catalyst is of relevance to the development of practical ORR catalysts for fuel cells. In addition, biomimetic catalysts of series 1,2,3, and 5, and catalyst 4b are the only metalloporphyrins studied in ORR catalysis with well-defined proximal and distal environments. For series 2, which is by far the most thoroughly studied series of biomimetic ORR catalysts, these well-defined environments result in an effective catalysis that seems to be the least sensitive among all metalloporphyrins to the electrode material (whether the catalyst is adsorbed or in the film) and to chemicals present in the electrolyte or in the O2 stream, including typical catalyst poisons (CO and CN ). 

Only three steps of the proposed mechanism (Fig. 18.20) could not be carried out individually under stoichiometric conditions. At pH 7 and the potential-dependent part of the catalytic wave (>150 mV vs. NHE), the —30 mV/pH dependence of the turnover frequency was observed for both Ee/Cu and Cu-free (Fe-only) forms of catalysts 2, and therefore it requires two reversible electron transfer steps prior to the turnover-determining step (TDS) and one proton transfer step either prior to the TDS or as the TDS. Under these conditions, the resting state of the catalyst was determined to be ferric-aqua/Cu which was in a rapid equilibrium with the fully reduced ferrous-aqua/Cu form (the Fe - and potentials were measured to be within < 20 mV of each other, as they are in cytochrome c oxidase, resulting in a two-electron redox equilibrium). This first redox equilibrium is biased toward the catalytically inactive fully oxidized state at potentials >0.1 V, and therefore it controls the molar fraction of the catalytically active metalloporphyrin. The fully reduced ferrous-aqua/Cu form is also in a rapid equilibrium with the catalytically active 5-coordinate ferrous porphyrin. As a result of these two equilibria, at 150 mV (vs. NHE), only <0.1%... 

Cobalt porphyrin derivatives were also reported129 to be active for electrochemical reduction of C02 to formic acid at an amalgamated Pt electrode. More recently, Becker et al have reported130 that Ag2+ and Pd2+ metalloporphyrins acted as homogeneous catalysts for C02 reduction in dry CH2C12 oxalic acid and H2 (its source was not clear) were produced, but no CO was detected. 

These reports sparked off an extensive study of metalloporphyrin-catalyzed asymmetric epoxidation, and various optically active porphyrin ligands have been synthesized. Although porphyrin ligands can make complexes with many metal ions, mainly iron, manganese, and ruthenium complexes have been examined as the epoxidation catalysts. These chiral metallopor-phyrins are classified into four groups, on the basis of the shape and the location of the chiral auxiliary. Class 1 are C2-symmetric metalloporphyrins bearing the chiral auxiliary at the... 

Asymmetric induction by metalloporphyrin is affected not only by the structure of the ligand, but also by other factors the nature of the metal center, the oxidant used, and the donor ligand added.62,63 As shown in Figure 1, oxo-metalloporphyrins have been considered to be the active species in metalloporphyrin-catalyzed oxidation. In some oxidations, however, metal-oxidant adducts have been suggested as the real active species. 

Pharmaceutical discoveries are principally made by thoughtful structural variation on a lead compound which has been found, by chance or design, to have a certain amount of the desired activity. It is clear that with metalloporphyrins, there are additional structural variations to be had. In the first place, it is possible to vary the metal. It was realized at an early stage that inserting and varying the metal would modify PDT activity.61 The possibility also exists of structural changes in axial ligands in those metalloporphyrins which possess them. This structural variation occurs in the space immediately above and below the macrocycle, which is a space not readily accessible to controlled variation in metal-free compounds of this series. 

Recently, the high inhibitory efficiency of metalloporphyrins has been shown in lipid peroxidation of rat brain homogenates [346]. It was found that manganese and cobalt porphyrins were very effective inhibitors of lipid peroxidation while iron and especially zinc porphyrins had very weak inhibitory activity, if any. For example, /50 values were equal to 21, 29, 212, 946 pmol 1 1 for CoTBAP, MnTBAP, FeTBAP, and ZnTBAP, respectively, where TBAP is 5,10,15,20-tetrakis [4-carboxyphenyl]porphyrin similar values were obtained for other porphyrin derivatives. 

The inhibition of lipid peroxidation by metalloporphyrins apparently depends on metal ions because only compounds with transition metals were efficient inhibitors. Therefore, the most probable mechanism of inhibitory effects of metalloporphyrins should be their disuniting activity. Manganese metalloporphyrins seem to be more effective inhibitors than Trolox (/5o = 204 pmol I 1) and rutin (/50 112 pmol I 1), and practically equal to SOD (/50= 15 pmol I 1). The mechanism of inhibitory activity of manganese and zinc metalloporphyrins might be compared with that of copper- and iron-flavonoid complexes [167,168], which exhibited enhanced antiradical properties due to additional superoxide-dismuting activity. 

Several other metal complexes have promising photodynamic activity and are currently under development (248). Metalloporphyrins inhibit the enzyme heme oxygenase for example, chromium porphyrin and mesoporphyrin are potent inhibitors of heme oxygenase both in vitro and in vivo (249, 250) and are being used for the treatment of the neonatal jaundice. 

Catalysis by various low-valent metalloporphyrins of the type already depicted in Section 3.7.2 (see reference lb for a precise list) is represented in Figures 4.3 and 4.4 for several cyclic and acyclic 1,2-dibromides. A striking example of the contrast between redox and chemical catalyses is shown in Figure 4.3a, with fluorenone anion radical on the one hand and iron(I) octaethylporphyrin on the other. Starting with the oxidized, inactive form of the catalyst, in each case—the active form is produced at a reversible wave. Addition of the same amount of 1,2-dibromocyclohexane triggers a catalytic increase in the current that is considerably less in the first... 

The use of models that mimic a protein active site is normally prompted by the desire to eliminate any influence of the polypeptide backbone surrounding the active site in real biological molecules, which may obscure its physico-chemical properties. The first attempts to synthesize metal complexes similar to the active site of haemoproteins, through the use of simple metalloporphyrin derivatives, failed. The failure was due to the fact that these complexes react irreversibly with dioxygen as a consequence of side autooxidative reactions of the type ... 

In the literature there are no quantitative studies on the kinetics and thermodynamics of stoichiometric superoxide reactions with metal centers in general, and metalloporphyrins in particular. More precisely, superoxide concentration and temperature dependent kinetic and thermodynamic measurements were never reported and consequently the rate constants, activation parameters or binding constants for this t5rpe of reactions (Scheme 15) are not known. (The catalytic rate constants for the superoxide disproportionation, i.e., dismutation, by metal complexes are known (see earlier), however in those measurements the concentration of a catalytic amount... 

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