Tetrapyrrolic compounds

A few examples to render tetrapyrrolic compounds less phototoxic can be found in the hterature. In one approach, carotenoid structures were employed for the synthesis of some carotenoporphyrin derivatives [92-94]. Figure 8 shows two stuctures by way of example. Due to similar photophysical properties of the two structural components, the excited triplet state of the porphyrin is quenched by the carotenoid moiety, thus inhibiting the formation of singlet oxygen, while its fluorescence capabilities are still preserved. Biodistribution studies revealed enhanced uptake into tumour tissue [39,93,95]. However, microscopy studies have shown that such compounds are associated with connective tissues in the tumors rather than with cancerous cells indicating low specificities for mahgnant transformation [96]. 

Some of the earliest attempts to prepare dehydrocorrin derivatives used a tetrapyrrole compound already containing a direct linkage between the two central rings. When its palladium(Il) derivative was treated with formaldehyde and hydrochloric acid it underwent cyclization but with the insertion of an oxygen atom rather than the desired carbon bridge (equation 51).261 Subsequent treatment of the same starting material with ammonia, methylamine or sodium sulfide gave rise to related macrocyclic products. 

The nomenclature of porphyrins, which belong to the larger class of tetrapyrrole compounds, is sometimes obscured by historical remnants (e.g. chlorin which does not contain any chlorine substituent, see H22c in fig. 10, or 2,4-di(o -methoxyethyl)-deuteroporphyrin for TMb, see fig. 11 below). IUPAC has published nomenclature rules in 19863 and the numbering adopted for the ring is given in fig. 10. The 5, 10, 15, and 20 positions are commonly referred to as meso positions the roman number after a name (I though IV) denotes the relative positions of substituents a and b. 

Despite the vast amount of reported OFETs with tetrapyrrole compounds as active semiconductors, the OFET performance of tetrapyrrole semiconductors is still very poor compared with the traditional inorganic semiconductors. On the basis of great potential applications of OFETs and the high theoretical charge transfer mobility of phthalocyanines, improving the OFET performance of existing phthalocyanine semiconductors and fabricating OFETs with novel phthalocyanine compounds will continue to draw the interests of scientists in future. 

This chapter reviews the occurrence, structure, and reactivity of chlorophyll catabolites from vascular plants and from some microorganisms. In parallel, synthetic means for obtaining such tetrapyrrolic compounds are recapitulated. The available structural information on chlorophyll catabolites (7) has provided a basis for deriving much of the current insights into the biochemical pathways of chlorophyll breakdown in plants and for complementary plant-biological work, as has been reviewed elsewhere recently (see Scheme 1) (2, 3, 4, 5, 6). 

Photodynamic therapy (PDT) is said to light-activate a photosensitizer accumulated in a tumor, but not in healthy cells, and which creates a photochemical reaction that selectively destroys the tumor cells. Prominently mentioned as activating agents are tetrapyrrol compounds (e.g., chlorophyll derivatives). 

Heme is synthesized from glycine and succinyl CoA, plus a metal (usually Fe). Heme is a tetrapyrrole compound. 

The a-oxoamine synthases family is a small group of fold-type I enzymes that catalyze Claisen condensations between amino acids and acyl-CoA thioesters (Figure 16). Members of this family are (1) 8-amino-7-oxononanoate (AON) synthase (AONS), which catalyzes the first committed step in the biosynthesis of biotine, (2) 5-aminolevulinate synthase (ALAS), responsible for the condensation between glycine and succinyl-CoA, which yields aminolevulinate, the universal precursor of tetrapyrrolic compounds, (3) serine palmitoyltransferase (SPT), which catalyzes the first reaction in sphingolipids synthesis, and (4) 2-amino-3-ketobutyrate CoA ligase (KBL), involved in the threonine degradation pathway. With the exception of the reaction catalyzed by KLB, all condensation reactions involve a decarboxylase step. 

A major metabolic fate of glycine is the biosynthesis of tetrapyrroles, compounds which contain four linked pyrrole rings. Four classes of these compounds include 1) Heme (an iron porphyrin) 2) Chlorophylls 3) Phycobilins (photosynthetic pigments of algae and 4) Cobalamins (Vitamin B12 and derivatives). 

Synthesis of Macrocyclic and Linear Tetrapyrrole Compounds Corrinoid Compounds in Edible Cyanobacteria... 

Early ecological studies suggested that certain cyanobacteria A. flos-aquae) are essential natural producers of the macrocyclic tetrapyrrole compound vitamin B12 (B12) [9,10]. With a molecular weight of 1355.4 Da, B12 is... 

Here, we reviewed recent studies that characterize the physiological functions of macrocylic and linear tetrapyrrole compounds from edible cyanobacteria. 

Macrocyclic tetrapyrrole compounds such as heme (iron), chlorophyll (magnesium), siroheme (iron), and E12 (cobalt) contain specific metal ions at the center of their tetrapyrrole rings [17]. Metal ion chelatases can be divided into two classes based on their structural architecture. Class 1 chelatases are heteromultimeric enzymes that require three gene products for efficient catalysis [18] of the ATP-dependent chelation reaction [19]. Enzymes in this class include chlorophyll and bacteriochlorophyll magnesium chelatases [18] and aerobic cobalt chelatase (CobNST) [20]. 

FIGURE 1 Biosynthesis of major macrocyclic and linear tetrapyrrole compounds in cyanobacteria. 

Propionic acid bacteria can synthesize a number of tetrapyrrole compounds corrinoids, heme, heme-containing enzymes, cytochromes, and linear tetrapyrroles. Biosynthesis of tetrapyrroles by all microorganisms starts with the formation of 5-aminolevulinic acid (ALA) (Corcoran and Shemin, 1957) and proceeds through the formation of porphobilinogen (PBG) and uroporphyrinogen (UPB) (Fig. 4.19A). Of the four possible isomers of uroporphyrinogenes, only the derivatives of UPB III are found in nature. 

Early stages of the biosynthesis of tetrapyrrole compounds are inhibited by hemin and by the complete form of vitamin B12 (Lascels and Hatch, 1969 Vitamin B represses specifically its own synthesis (Bykhovsky et al., 1968, 1975a). The inhibiting effect of oxygen on vitamin Bn synthesis was attributed to the repression of ALA dehydratase and ALA synthase activities (Menon and Shemin, 1967), but now it is believed (Oh-hama et al., 1993) that in propionic acid bacteria ALA is formed in the C5 pathway. Bykhovsky... 

To summarize, corrinoids in propionic acid bacteria are involved not onh in fermentation, but also in such important anabolic processes as protein and DNA synthesis and DNA methylation. In this respect, corrinoids differ from other related tetrapyrrole compounds by their polyfunctionalit. The involvement of corrinoid-dependent enzymes in different metabolic processes in propionibacteria explains the propensity of anaerobic strains of the classical propionic acid bacteria to synthesize large amounts of corrinoids under suitable conditions. 

Chemical synthesis of PBG, based on the formation of pyrroles, includes more than 10 steps and gives the product with a yield of 25%. In chemical synthesis from ALA, the yield of PBG is about 10%. Microbiological methods using ALA as a substrate have a good perspective, since the product yield can reach up to 54%. Propionibacteria present a special interest for PBG production, since they have a high natural capacity for the synthesis of tetrapyrrole compounds, for which PBG is a common precursor. 

Bykhovsky VY (1979) Biogenesis of tetrapyrrole compounds (porphyrins and corrinoids), and its regulation. In Zagalak B and Friedrich W (eds) Vitamin B12, pp 293-314. Walter de Gruyter, Berhn... 

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