Protoporphyrins

Hemin is the complex between protoporphyrin and iron in the +3 oxidation state. Iron is in the +2 state in the heme of hemoglobin. The molecule has the following structure ... 

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... 

Erythrocyte protoporphyrin (EF) elevation in males Erythrocyte protoporphyrin (EP) elevation in females ALA-D inhibition... 

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. 

Friedrieh has studied the free-base eytoehrome c in a glass state at 1.6 K (96MI77). In general, for free-base protoporphyrins it ean be safely assumed that the hole-burning photoreaetion is based on a light-indueed rearrangement of the inner protons. This type of reaetions has been verified for all free-base porphyrin moleeules [92MI(61)381]. 

The synthesis of porphyrins from monopyrrolic, dipyrrolic, tripyrrolic and tctrapyrrolic precursors requires, even for an experienced porphyrin chemist, a substantial amount of time and effort to accomplish. As an alternative to these total synthetic routes, nature provides a source of prefabricated porphyrins. Among the several porphyrins which can be isolated from natural material,s the red blood pigment heme, protoporphyrin dimethyl ester81 b and hemato-porphyrin, both derived from heme, are the only compounds which can be obtained in sufficient amounts. Heme is available in almost unlimited amounts from slaughter-house waste. From 1 L of blood ca. 1 g of heme can be isolated.81 b Currently, heme is offered commercially by chemical retailers at a relatively low price so that is cheaper to buy hemin than to perform a self-isolation in the laboratory. 

When hemin (1) is treated with gaseous hydrogen chloride in anhydrous methanol/pyridine in the presence of iron(II) sulfate, protoporphyrin dimethyl ester (2), the metal-free ligand of hemin. is produced in almost quantitative yield. This compound is quite sensitive to oxygen... 

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. 

The modification of porphyrins leading to isobacteriochlorins by C —C-bond formation is important to obtain a wide range of structurally different isobacteriochlorins which can then be further transformed. Protoporphyrin, deutoroporphyrin and hematoporphyrin (readily accessible from red blood pigment) are interesting and useful starting materials in the synthesis of isobacteriochlorins. 

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. 

Heme (C34H3204N4Fe) represents an iron-porphyrin complex that has a protoporphyrin nucleus. Many important proteins contain heme as a prosthetic group. Hemoglobin is the quantitatively most important hemoprotein. Others are cytochromes (present in the mitochondria and the endoplasmic reticulum), catalase and peroxidase (that react with hydrogen peroxide), soluble guanylyl cyclase (that converts guanosine triphosphate, GTP, to the signaling molecule 3, 5 -cyclic GMP) and NO synthases. 

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... 

Zinc protoporphyrin in blood After 1 month exposure 2 50 pg/100 ml erythrocytes or lOOpg/IOOmI blood B... 

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. 

Formation of Heme Involves Incorporation of Iron Into Protoporphyrin... 

The final step in heme synthesis involves the incorporation of ferrous iron into protoporphyrin in a reaction catalyzed by ferrochelatase (heme synthase), another mitochondrial enzyme (Figure 32-4). 

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