Protoporphyrin- IX

Protoporphyrin-IX (36). FT C n.m.r. was used to good advantage to investigate the biosynthetic origin of the meso-carbons of protoporphyrin-IX methyl ester (36). Initially, the C chemical shifts of a series of porphyrins at natural abundance were determined. These resonances are tabulated in Table 17. The assignment of the sharp side-chain signals was made by comparison within the spectra of the four model porphyrins (36), (37), (38), and (39) 

The precursor employed for the tracer experiment, [ 11- C]porphobilinogen, PBG (40), was prepared by reductive methylation of (41) with 60 % C-enriched formaldehyde to give (42), which was chlorinated to (43). The chloro-compound was converted into the azide (44) with sodium azide. The azide (44) was hydrogenated to the amine, which produced an intermediate lactam, then (40). 

Incubation of (40) with an enzyme system from Euglena gracilis produced protoporphyrin-IX (35), which was isolated as its methyl ester. The FT 

This study established that the meso-carbons of protoporphyrins are derived from C-11 of PBG (40) and that these positions are equally labelled. 

Since degradative procedures for vitamin B 2 were not adequate to determine the origin of the C-l-methyl group, two groups of workers simultaneously investigated this problem with the aid of FT C n.m.r. spectroscopy and C-labelled precursors. 

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Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

HEMOPROTEINS. These proteins are actually a subclass of metalloproteins because their prosthetic group is heme, the name given to iron protoporphyrin IX (Figure 5.15). Because heme-containing proteins enjoy so many prominent biological functions, they are considered a class by themselves. 

Cytochromes were first named and classified on the basis of their absorption spectra (Figure 21.9), which depend upon the structure and environment of their heme groups. The b cytochromes contain iron—protoporphyrin IX (Figure 21.10), the same heme found in hemoglobin and myoglobin. The c cytochromes contain heme c, derived from iron-protoporphyrin IX by the covalent attachment of cysteine residues from the associated protein. UQ-cyt c... 

FIGURE 21.10 The structures of iron protoporphyrin IX, heme c, and heme a. 

In numerous synthetic studies,9" 6 100 it has been demonstrated that porphyrins react at the chromophore periphery in cycloaddition reactions, rearrangements, conjugative additions and substitution reactions to yield interesting porphyrin derivatives. Thus, metal-free protoporphyrin IX dimethyl ester reacts in Diels-Alder reactions108a b with dienophilcs like ethenetetra-carbonitrile and acetylenedicarboxylates at the diene structural parts to yield, according to the reaction conditions, the corresponding monoadducts 2 and 3 (see also Section 1.2.) and bisadducts 1 (see also Section 1.4.), respectively. 

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

The spectral features of the complexes (R2SnCl)2 protoporphyrin IX are in agreement with the monomeric character of protoporphyrin IX. 

Hyjjerbilirubinaemia is an abnormality observed mainly in neonates in whom the liver is insufficiently developed to be able to detoxify the bile pigment bilirubin. This situation is known as neonatal jaundice and can sometimes become a serious disease causing neurotoxic symptoms. Bilirubin is produced by the degradation of heme [the Fe(II) complex of protoporphyrin IX] by heme oxygenase to give biliverdin, which is reduced by biliverdin reductase to... 

Heme and its immediate precursor, protoporphyrin IX (Figure 32-4), are both type III porphyrins (ie, the methyl groups are asymmetrically distributed, as in type III coproporphyrin). However, they are sometimes identified as belonging to series IX, because they were designated ninth in a series of isomers posmlated by Hans Fischer, the pioneer worker in the field of porphyrin chemistry. 

Hemoproteins, such as hemoglobin and the cytochromes, contain heme. Heme is an iron-porphyrin compound (Fe -protoporphyrin IX) in... 

Esterification of the propionic acid side chain at C-13 (ring C) with a methyl group catalyzed by S-adenosyl-L-methionine-magnesium protoporphyrin 0-meth-yltransferase yields protoporphyrin IX monomethyl ester (MPE), which originates protochlorophyllide by a P-oxidation and cyclization of the methylated propionic side chain. This molecule contains a fifth isocyclic ring (ring E), the cyclopentanone ring that characterizes aU chlorophylls. 

FIGURE 2.1.4 Biosynthesis steps of porphyrins from ALA to protoporphyrin IX. 

FIGURE 2.1.5 Biosynthesis steps of porphyrins from protoporphyrin IX to chlorophyll a. 

The NIS investigation of heme complexes includes various forms of porphyrins (deuteroporphyrin IX, mesoporphyrin IX, protoporphyrin IX, tetraphenylpor-phyrin, octaethylporphyrin, and picket fence porphyrin) and their nitrosyl (NO) and carbonyl (CO) derivatives, and they have been the subject of a review provided by Scheidt et al. [109]. 

Maldotti (96) studied the kinetics of the formation of the pyrazine-bridged Fe(II) porphyrin shish-kebab polymer by means of flash kinetic experiments. Upon irradiation of a deaerated alkaline water/ethanol solution of Fe(III) protoporphyrin IX and pyrazine with a short intense flash of light, the 2 1 Fe(II) porphyrin (pyrazine)2 complex is formed, but it immediately polymerizes with second-order kinetics. This can be monitored in the UV-Vis absorption spectrum, with the disappearance of a band at 550 nm together with the emergence of a new band due to the polymer at 800 nm. The process is accelerated by the addition of LiCl, which augments hydrophobic interactions, and is diminished by the presence of a surfactant. A shish-kebab polymer is also formed upon photoreduction of Fe(III) porphyrins in presence of piperazine or 4,4 -bipyridine ligands (97). 

Although oxygen was found to be the only oxidant for conversion of coproporphyrinogen III to protoporphyrin IX, anaerobic systems must obviously exist for the biosynthesis of the latter molecule (43). Porphine itself has not been found in nature but spectral lines identical to those of bis-pyridylmagnesiumtetrabcnzoporphine have been detected in interstellar space (53). 

In tracing the evolutionary development of iron ligands it is of interest to examine the machinery employed by organisms which carry out reactions on those substances believed to have been present on the primitive Earth. Specific substrates acted on by this group include, besides ferrous iron itself, hydrogen sulfide, hydrogen gas, methane and reduced nitrogen compounds. Species which perform photosynthesis may be presumed to have the capacity to synthesize protoporphyrin IX since this substance is an intermediate in chlorophyll biosynthesis (43). 

Figure 8.1 Heme (iron protoporphyrin IX) structure. The most frequently observed cleavages in LDMS of the intact species are denoted. Heme elemental composition is C34H32N404Fe monoisotopic molecular mass is 616.176 Da average molecular mass is 616.487 Da.

Figure 7.2 (a) Schematic representation of the structure of B. subtilis ferrochelatase. Domain I is coloured green and domain II blue. The parts of the chain in red build up the walls of the cleft, and the region in yellow makes the connection between the domains. The N- and C-termini are marked, (b) The proposed active site of ferrochelatase with protoporphyrin IX molecule (red) modelled into the site. The backbone atoms of the protein are in purple, the side-chains in blue. Reprinted from Al-Karadaghi et ah, 1997. Copyright (1997), with permission from Elsevier Science. 

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