Porphyrin protoporphyrin

Gradient HPLC system identical to that used for urinary porphyrins. Protoporphyrin present only in feces but not in urine elutes last. If it is not eluted, the plateau phase can be prolonged for some minutes. 

Some of the key properties of a photosensitizer are high efficiency of singlet-oxygen generation, strong absorption in the red and particularly near-IR (660-800 nm), preferential affinity for tumor rather than healthy tissue, and rapid clearance from the body. Porphyrin and phthalocyanine dyes fit these criteria best, and much work has been done on these dye types [76], Photofrin, a hemato-porphyrin derivative, was the first photosensitizer to be approved for clinical use. It is a complex mixture of monomeric porphyrins (protoporphyrin, hematopor-phyrin (84), and hydroxyethylvinyldeuteroporphyrin) and oligomers of these porphyrins. 

El-Far, M. and Pimstone, N. (1984) Porphyrin Protoporphyrin Plasma Protein Interaction - The Metabolic Basis for Tumor Localization of Hematoporphyrin Derivative - A Preliminary Report... 

Figure 38 5 Short term Fe uptake rates from model iron/ligand complexes hy Trichodesmium colonies collected in the suhtropical Atlantic Ocean. Shown are uptake rates from Fe complexed to a trihydroxamate siderophore (desferrioxamine), a dihydroxamate siderophore (rhodoturulic acid), and a porphyrin (protoporphyrin IX). For comparative purposes, uptake rates were also measured using added inorganic Fe (111). Achilles et al. (2003), Limnology and Oceanography 48 2250-2255.

In the presence of oxygen, dissolved hemoglobin is slowly oxidized to methemoglobin, a derivative of hemoglobin in which the iron is present in the ferric (Fe +) state. In metHb, the ferric ion is bound tightly to a hydroxyl group or to some other anion. The heme porphyrin (protoporphyrin IX) that contains an Fe + ion is known as hemin. 

The structure of one of the most important of the porphyrins, protoporphyrin-9 (as the iron complex), is diown in Fig. 1. 

Chisolm, J.J. and Brown, P. (1975) Micro-scale photofluorometric determination of free erythrocyte porphyrin (protoporphyrin IX). Clin. Chem., 21, 1669-1682 Dietrich, K.N., Krafft, K.M., Shukla, R., Bomschein, R.L. and Succop, P.A. (1986) The neurobehavioral effects of prenatal and early postnatal lead exposure. In Schroeder, S.R. (ed.). Toxic Substances and Mental Retardation Neurobehavioral Toxicology and Teratology (Washington, DC AAMD Monograph Series)... 

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. 

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. 

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. 

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. 

The porphyrinogens described above are colorless, containing six extra hydrogen atoms as compared with the corresponding colored porphyrins. These reduced porphyrins (the porphyrinogens) and not the corresponding porphyrins are the actual intermediates in the biosynthesis of protoporphyrin and of heme. 

High levels of lead can affect heme metabohsm by combining with SH groups in enzymes such as fer-rochelatase and ALA dehydratase. This affects porphyrin metabolism. Elevated levels of protoporphyrin are found in red blood cells, and elevated levels of ALA and of coproporphyrin are found in urine. 

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

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). 

LDMS is particularly well suited for the analysis of porphyrins.35-39 The heme molecule—a 22 rc-electron conjugated protoporphyrin system (Figure 8.1)—is an efficient photo-absorber in the visible and near UV (with an absorption maximum—the Soret band—near 400nm). This feature, concurrently with its low ionization potential, warrants that direct LDMS will possess extremely low limits for heme detection. The uses of IR or UV LDMS for structural characterization of natural porphyrins and their metabolites, synthetic monomeric porphyrins (e.g., used in photodynamic therapy), porphyrin polymers, and multimeric arrays, have been well documented.41148 In addition fast atom bombardment MS has been used to characterize purified hemozoin, isolated from the spleens and livers of Plasmodium yoelii infected mice.49... 

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