Porphyrins cofactors

Porphyrin Cofactors Their Advantages and Irreversible Metal Insertion. 215... 

The above account of selectivity of inorganic plus organic chemistry in synthesis is given rather extensively to stress three points. All the four (Mg, Fe, Co and Ni) porphyrin products came from one source, the synthesis of uroporphyrin. The basis of selection is very different from that in primitive centres which use thermodynamic stability constant selectivity based on different donor atoms for different metal ions. Here, all ion complexes have the same donor atoms, nitrogen, the most constrained being the coordination of Mg2+ by five nitrogens exactly as is seen for Fe in haemoglobin. Hence, there also has to be a new control feedback to ensure that the appropriate quantities of each metal cofactor is produced in a balanced way, that is synthesis from uroporphyrin has to be divided based upon... 

When one of the Fe-coordinating Ns of the porphyrin is made inequivalent to the others, for example, by pulling on it, or by putting a protein structure around the cofactor, then the molecular x axis and y axis become inequivalent, and the axial EPR spectrum turns into the rhombic spectrum in trace d with derivative trace e (see also Table 5.4). There are now three features in the spectrum a peak, a zero crossing, and a negative peak, and their field positions closely (exactly for zero linewidth) correspond to those of the g-values, gx, gy, and gz. Finally, in trace f of Figure 5.4, which is the experimental X-band spectrum of cytochrome c, it can be seen that not only the g-value (peak position) but also the linewidth is frequently found to be anisotropic. This extra complication will be discussed extensively in Chapter 9. 

A comparison of porphyrin and pincer activity rationalized through reactivity index Porphyrin and pincer complexes are both important categories of compounds in biological and catalytic systems. Structure, spectroscopy, and reactivity properties of porphyrin pincers are systematically studied for selection of divalent metal ions. It is reported that the porphyrin pincers are structurally and spectroscopically different from their precursors and are more reactive in electrophilic and nucleophilic reactions. These results are implicative in chemical modification of hemoproteins and understanding the chemical reactivity in heme-containing and other biologically important complexes and cofactors [45]. 

As we will see in subsequent chapters, many metalloproteins have their metal centres located in organic cofactors (Lippard and Berg, 1994), such as the tetrapyrrole porphyrins and corrins, or in metal clusters, such as the Fe-S clusters in Fe-S proteins or the FeMo-cofactor of nitrogenase. Here we discuss briefly how metals are incorporated into porphyrins and corrins to form haem and other metallated tetrapyrroles, how Fe-S clusters are synthesized and how copper is inserted into superoxide dismutase. 

After a postdoc in the US (Professor S. J. Benkovic, Pennsylvania State University) where he worked on catalytic antibodies, he was appointed in 1996 as Directeur de Recherches in the CNRS in the Laboratory of Pharmacological and Toxicological Chemistry and Biochemistry (Director Dr. D. Mansuy), at Paris 5, where he developed the field of hemoabzymes catalytic antibodies with an iron-porphyrin cofactor. ... 

Corphin is the F-430 cofactor found in methyl-coenzyme M reductase, a nickel-containing enzyme that participates in the conversion of carbon dioxide to methane in methanogenic bacteria. The nickel ion in F-430 is coordinated by the tetrahydrocorphin ligand, which contains structural elements of both porphyrins and corrins. 

A tetrapyrrole (related to porphyrins and corrins) containing a nickel ion. This cofactor, corphin, is a crucial component of methyl-coenzyme M reductase, a bacterial enzyme participating in the formation of methane. 

Several additional studies were carried out to obtain information about the precise behavior of the various components in the model system. The interplay between the manganese porphyrin and the rhodium cofactor was found to be crucial for an efficient catalytic performance of the whole assembly and, hence, their properties were studied in detail at different pH values in vesicle bilayers composed of various types of amphiphiles, viz. cationic (DODAC), anionic (DHP), and zwitterionic (DPPC) [30]. At pH values where the reduced rhodium species is expected to be present as Rh only, the rate of the reduction of 13 by formate increased in the series DPPC < DHP < DODAC, which is in line with an expected higher concentration of formate ions at the surface of the cationic vesicles. The reduction rates of 12 incorporated in the vesicle bilayers catalyzed by 13-formate increased in the same order, because formation of the Rh-formate complex is the rate-determining step in this reduction. When the rates of epoxidation of styrene were studied at pH 7, however, the relative rates were found to be reversed DODAC DPPC < DHP. Apparently, for epoxidation to occur, an efficient supply of protons to the vesicle surface is essential, probably for the step in which the Mn -02 complex breaks down into the active epoxidizing Mn =0 species and water. Using a-pinene as the substrate in the DHP-based system, a turnover number of 360 was observed, which is comparable to the turnover numbers observed for cytochrome P450 itself. 

Coenzyme B12 is the cofactor form of vitamin B 2, which is unique among all the vitamins in that it contains not only a complex organic molecule but an essential trace element, cobalt. The complex corrin ring system of vitamin B12 (colored blue in Fig. 2), to which cobalt (as Co3+) is coordinated, is chemically related to the porphyrin ring system of heme and heme proteins (see Fig. 5-1). A fifth coordination position of cobalt is filled by dimethylbenzimidazole ribonucleotide (shaded yellow), bound covalently by its 3 -phosphate group to a side chain of the corrin ring, through aminoisopropanol. 

The search for RNAs with new catalytic functions has been aided by the development of a method that rapidly searches pools of random polymers of RNA and extracts those with particular activities SELEX is nothing less than accelerated evolution in a test tube (Box 26-3). It has been used to generate RNA molecules that bind to amino acids, organic dyes, nucleotides, cyano-cobalamin, and other molecules. Researchers have isolated ribozymes that catalyze ester and amide bond formation, Sn2 reactions, metallation of (addition of metal ions to) porphyrins, and carbon-carbon bond formation. The evolution of enzymatic cofactors with nucleotide handles that facilitate their binding to ribozymes might have further expanded the repertoire of chemical processes available to primitive metabolic systems. 

Metal ion chelates of various porphyrins, differing in their substituents at positions 1-8, are intimately involved in a great number of life processes. Iron protoporphyrin (13) is the most common form and serves as the cofactor of a large number of enzymes. Usually (13) is non-covalently bound to its conjugate apoenzymes. Examples of covalently attached (13) are provided by c-type cytochromes, the attachment being between two vinyl side chains of (13) and two cysteine residues of the protein. Other biologically important derivatives of porphyrin include chlorophyll a (14), bacteriochlorophyll a and heme a (B-79MI11002). 

The monooxygenases [65-70] are characterized by the axial attachment of the heme cofactor to a thiolate functionality from a cysteine residue of the protein matrix. The binding pockets of monooxygenases are usually organized in such a way as to lead the substrate directly to the active FeO subunit of the porphyrin. This... 

As for the peroxidases, Compound I and water are formed in the first step from one equivalent of hydrogen peroxide and the resting state of the catalase. The back-reaction, however, does not proceed via Compound II but rather via a two-electron-two-proton transfer cascade, in which both hydrogen atoms of a second molecule of hydrogen peroxide are transferred to the ferryl subunit of the porphyrin cofactor. Due to the similarity of catalases and peroxidases, it is not too surprising that this reaction is also catalyzed by most peroxidases. Alternatively, catalases and some peroxidases react with alkyl hydroperoxides via the respective alkanol to an aldehyde or ketone (Scheme 2.17). A requirement for this reaction is an easily accessible active site for the hydroperoxide, so that only those peroxidases with open access such as CPO or CiP are able to promote this reaction. 

In comparison with metal porphyrins, the corresponding metal phthalocyanines are much more stable against oxidative decomposition. Murahashi et al. reported that chlorinated Fe(II) phthalocyanine is particularly well suited for aerobic allylic oxidation employing acetic aldehyde as a cofactor (Scheme 3.27) [118]. Under these conditions, cyclohexene la is converted to a mixture of 2a and 3a in 70% overall yield and the epoxide 4a as byproduct (30%). Acetic aldehyde is proposed to autoxidize by... 

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