Pyropheophorbide

It is interesting to note that the magnesium or zinc complexes of methyl pheophorbide a (11, M = Mg, Zn R = C02Me) or methyl pyropheophorbide a (11, M = Mg, Zn R = H) are cleaved between positions 20 and 1 by singlet oxygen, whereas in contrast nature cleaves the chlorin at the 4,5-C —C double bond.44-45a h46 The ring fission at the 4.5-C —C double bond can be achieved with the cadmium(II) complex of methyl pheophorbide (11, M = Cd R = C02Me) to produce 12.43i... 

Furthermore some O- and. S -glycosylated pyropheophorbide-a derivatives have been prepared.75 The O-glycosylated pyropheophorbide derivative 97 was obtained by carbohydrate per-acetate glycosylation acid catalyzed method of derivative 96 (Fig. 10). The reagent proportions and the reaction times have been shown to rule the reaction yield. The best results were found when the reagents ratio was 2 1 2 (glycoside pyropheophorbide Lewis acid). Under these conditions the reaction yield was 36% with 83% of anomeric purity. The glycosylated derivatives 97 are diastereomeric mixtures. 

For the preparation of S -glycosylated pyropheophorbide derivatives 137-140 (Fig. 12), chlorin 136 was gradually added to a suspension of the... 

Chlorophyll-a Pheophytin-a Pyropheophitin- a Pheophorbide-a Pyropheophorobide-a Isofucoxanthin-dehydrate Fucoxanthin dehydrate Fucoxanthin-hemiketal Isofucoxanthin dehydrate pheophorbide a ester Isofucoxanthin dehydrate pheophorbide a ester Isofucoxanthin dehydrate pyropheophorbide a ester 23.5 26.4 28.1 5.0 6.9 10.7 12.0 6.4 24.4 22.9 25.4... 

Fig. 2.133. HPLC chromatogram of pigment extracts from table olives cv. Gordal (a) healthy fruits and (b) altered fruits. Peaks 1 = 15-glyoxilic acid pheophorbide-b 2 = 15-glyoxilic acid pheophorbide-a 3 = Cu-15-glyoxilic acid pheophorbide-a 4 = pheophorbide-b 5 = pheophorbide-a 6 = pyropheophorbide-a 7 = 15-glyoxilic acid pheophytin-b 8 = Cu-15-glyoxilic acid pheophytin-b 9 = 15-glyoxilic acid pheophytin-a 10 = Cu-15-glyoxilic acid pheophytin-a 11 = 15 -OH-lactone-pheophytin-b 12 = 15 -OH-lactone-pheophytin-a 13 = 15-formylpheophytin-b 14 = pheophytin-b 14 = pheophytin-b 15 = 15-formylpheophytin-a 16 = pheophytin-a 16 = pheophytin-a 17 = pyropheophytin-b 18 = Cu-pheophytin-a 19 = Cu-15-formylpheophytin-a 20 = pyropheophytin-a 21 = Cu-pyropheophytin-a. Reprinted with permission from B. Ganul-Rojas el al. [304].

Rancan F, Helmreich M, Molich A, JuxN, Hirsch A, Roder B, Witt C, Bohm F (2005) Fullerene-pyropheophorbide a complexes as sensitizer for photodynamic therapy uptake and photo-induced cytotoxicity on Jurkat cells. J Photochem Photobiol B 80 1-7. 

Figure F4.4.2 HPLC chromatogram of chlorophyll derivatives separated using the Alternate Protocol. Peak identifications 1, chlorophyllide if 2, chlorophyllide a 2, chlorophyllide a" 3, pheophorbide tr, 3, pheophorbide if 4, pyropheophorbide b 5, pheophorbide a 5, pheophorbide a 6, pyropheophorbide a 7, chlorophyll tr, 7, chlorophyll if 8, chlorophyll a 8, chlorophyll a 9, pheophytin tr, 9, pheophytin tf 10, pyropheophytin tr, 11, pheophytin a 11, pheophytin a 12, pyropheophytin a. Reproduced from Canjura et al. (1991) with permission from the Institute of Food Technologists.

Fig. 2 Examples of photosensitizers presently approved for clinical applications or in clinical studies. mTHPC, tetra (meso-hydroxy) phenyl chlorin BPD-MA, benzoporphyrin derivative Photofrin is a mixture of several compounds where dimers or trimers of the indicated structure are assumed to be of major importance PpIX, protoporphyrin IX - accumulating upon treatment with 5-aminolevulinic acid or its ester derivatives, NPe6, HPPH, Hexyl pyropheophorbide TPPS2a, disulfonated (adjacent) tetraphenylporphin AlPcS2a, disulfonated (adjacent) aluminum phthalocyanine. Areas with ionic side groups are indicated in shadow...

Methyl ester of meso-pyropheophorbide 6 Methyl ester of meso-pyropheophorbide 6-3-methanol (15 minutes) i-CjH7(CJ 22. ... 

Methyl ester of 9-hy-droxydesoxo-meso-pyropheophorbide b- -methanol (2 to 4 hours) i-CsH7(C) 22... 

Although covalently linked donor-acceptor systems of small organic chromo-phores have been studied for some time in order to uncover the basic principles of electron and energy transfer, the first covalently linked cyclic tetrapyrroles were reported by Gouterman, Dolphin and coworkers in 1972 [27]. In 1976 the first dimeric chlorophyll-based models were reported. Structure la, based upon pyropheophorbide-a, was prepared by Boxer and Closs [28], whereas the pheo-phorbide-a derivative lb was reported by Wasielewski, Studier and Katz [29]. 

As mentioned above, the natural photosynthetic reaction center uses chlorophyll derivatives rather than porphyrins in the initial electron transfer events. Synthetic triads have also been prepared from chlorophylls [62]. For example, triad 11 features both a naphthoquinone-type acceptor and a carotenoid donor linked to a pyropheophorbide (Phe) which was prepared from chlorophyll-a. The fluorescence of the pyropheophorbide moiety was strongly quenched in dichloromethane, and this suggested rapid electron transfer to the attached quinone to yield C-Phe+-Q r. Transient absorption studies at 207 K detected the carotenoid radical cation (kmax = 990 nm) and thus confirmed formation of a C+-Phe-QT charge separated state analogous to those formed in the porphyrin-based triads. This state had a lifetime of 120 ns, and was formed with a quantum yield of about 0.04. The lifetime was 50 ns at ambient temperatures, and this precluded accurate determination of the quantum yield at this temperature with the apparatus employed. 

Figure 9.37 Chemical structures of chlorophylls-a and b which contain a propionic acid esterified to a C20 phytol chlorophylls-cj and C2 have an acrylic acid that replaces the propionic acid. Also included are the pheopigments, the four dominant tetrapyrrole derivatives of chloropigments (pheopigments) found in marine and fresh-water/estuarine systems (chlorophyllide, pheophorbide, pheophytin, pyropheophorbide.) More specifically, chlorophyllase-mediated de-esterification reactions (loss of the phytol) of chlorophyll yield chlorophyllides. Pheophytins can be formed when the Mg is lost from the chlorophyll center. Pheophorbides are formed from removal of the Mg from chlorophyllide or removal of the phytol chain from pheophytin, and pyrolyzed pheopigments, such as pyropheophorbide and pyropheophytin, are formed by removal of the methylcarboxylate group (-COOCH3) on the isocylic ring from the C-13 propionic acid group.

Pheophorbide-fc Chlorophyllide-a Blue-green chl-a derivatives (lactones, 10-hydroxy chlorophylls) Pyrochlorophyll-a Pyropheophytin-a Pyropheophorbide-a Mesopheophorbide-a... 

King, L.L., and Repeta, D.J. (1994) Novel pyropheophorbide steryl esters in Black Sea... 

A high concentration of chlorophyll catalyzes photosensitized reaction (photooxidation) in the product fried and stored in clear packages. In addition, extra bleaching of the oil can decompose chlorophylls into pheophytenes, pheophorbides, and pyropheophorbides, which do not have visual green color but are ten times more active photosensitizers than their parent compounds (44- 6). 

The crude oil with high nonhydratable phospholipids requires acid pretreatment before refining. This may increase the chlorophyll breakdown, forming pheophy-tenes, pheophorbides, and pyropheophorbides and make the finished oil more susceptible to photooxidation (44). 

Chlorophyll itself is rather unstable due to facile reactions at the 10 position. Pyropheophorbides, which lack substituents at this position, are much more stable and synthetically tractable. Thus, pyropheophorbide a, prepared from natural chlorophyll a, was used as the basis for triad 13 [58]. 

The pyropheophorbide skeleton bears a carotenoid polyene and a naphthoquinone derivative. The naphthoquinone is substituted with a bromine atom in order to increase its electron accepting abilities, and therefore the photoinitiated electron transfer rate from the tetrapyrrole. 

Information regarding the solution conformation of 13 was derived from the pyropheophorbide ring current induced shifts in the resonance positions of the carotenoid and quinone moieties. These two species were found to be extended away from the tetrapyrrole, rather than folded back across it. The absorption spectrum of 13 was essentially identical to the sum of the spectra of model compounds. The pyropheophorbide fluorescence, however, was strongly quenched by the addition of the quinone. This implies the formation of a C-Phe -Q state via photoinitiated electron transfer from the pyropheophorbide singlet state, as was observed for C-P-Q triads (see Figure 4). Excitation of the molecule in dichloromethane solution at 207 K with a 590 nm laser pulse led to the observation of a carotenoid radical cation transient absorption. Thus, the C-Phe -Q " state can go on via an electron transfer step analogous to step 4 in Figure 4 to yield a final C -Phe-Q state. This state had a lifetime of 120 ns. The quantum yield at 207 K was 0.04. At ambient temperatures, the lifetime of the carotenoid radical cation dropped to about SO ns, and the quantum yield could not be determined accurately because of the convolution of the decay into the instrument response function. 

As shown in Figure 20, the excitation spectrum for pyropheophorbide fluorescence does not appear to include any significant contribution from light absorbed by the carotenoid moiety. Quantitatively, singlet energy transfer must be less than ca. 7%, which is the limit of error in these measurements. 

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