Chlorophyllin derivatives

Fig. 2.137. Left electrophoregram of chlorophyll pigments in fresh extra virgin olive oil, added with copper chlorophyllin (1) chlorophyllin B (2) pheophytin B (3) pheophytin B(4) chlorophyllin A (5) pheophytin A (6) pheophytin A (7) copper chlorophyllin. Right electrophoregram of chlorophyll pigments in extra virgin olive oil, with a long shelf-life, added with copper chlorophyllin (1) chlorophyllin B (2) chlorophyllin derivatives (3) chlorophyllin A (4) copper chlorophyllin. Reprinted with permission from L. Del Giovine et al. [308].

Chiu, L.C.-M., Kong, C.K.-L., Ooi, V.E., 2003. Antiproliferative effect of chlorophyllin derived from a traditional Chinese medicine Bomhyx mori excreta on human breast cancer MCF-7 cells. International Journal of Oncology 23 (3), 729-735. 

Despite their low (photo)stability, chlorophylls, or rather their derivatives, have found some applications, especially in the nutrition industry. In Europe the food additive E140 is chi, and E141 is chlorophyllin (a semisynthetic sodium/copper derivative of chlorophyll), and they are used in cakes, beverages, sweets, icecream etc. As color No 125 they find applications in toothpaste, as a soap pigment and in shampoos. The older literature also... 

Porphyrin [125-128] and phthalocyanine [129] derivatives are also employed as photosensitizers in DSSCs. A nanocrystalline Ti02 solar cell sensitized by Cu chlorophyllin produced 2.6% efficiency (./ . = 9.4 mA/cm2 and Voc = 0.52 V) under 100 mW/cm2 [127]. In order to develop new, efficient, metal dye photosensitizers, both an increase in the absorption coefficient of the metal complex and a greater red shift of the absorption spectrum is required. 

The clastogenic effects of male Swiss albino mice fed chromium(VI) trioxide (20 mg/kg body weight) by gavage were studied after 24 hours, bone marrow cells were isolated and 500 metaphase plates were scored for chromosomal aberrations (Sarkar et al. 1993). The treated cells showed a significant increase in aberrations per cell over controls by 4.4-fold. When animals were treated simultaneously with chlorophyllin (1.5 mg/kg), a sodium-copper derivative of chlorophyll and an antioxidant, numbers of aberrations were reduced to nearly background levels. 

The best source for Chi a is the cyanobacterium Spirulina platensis, which is available commercially. Chi a/b mixtures can be obtained from all green plants. All other Chls are less readily accessible, which limits their applications. Several Chi derivatives are used as dyes for food colorants (Cu-chlorophyllin) and cosmetics. The chlorophyll used for the latter is a complex mixture of degradation products. More recently, (B)Chl derivatives have gained increasing interest as photosensitizers in photodynamic therapy of cancer, these compounds include pigments in which the isocyclic ring is opened and/or the central metal has been removed or replaced (e.g., by Pd" " ) to increase phototoxcicity (12, 13). 

Chlorophylls and pheophytins are lipophylic, due to the presence of the phytol group, while chlorophyllins and pheophorbids without phytol are hydrophylic. The copper complexes of both pheophytin and pheophorbid have the metal firmly bound it is not liberated even by the action of concentrated hydrochloric acid, and it is not removed to any appreciable extent upon metabolism thus it is acceptable for the coloration of foodstuffs. Both coppered and uncoppered chlorophyll and their derivatives are available as food colorants. 

Copper Chlorophyll. Current efforts to improve the green color of processed foods include the use of copper complexes of chlorophyll derivatives. Copper complexes of pheophytin and pheophorbide are available commercially under the names copper chlorophyll and copper chlorophyllin, respectively. Their use in canned foods, soups, candy, and dairy products is permitted in most European countries under regulatory control of the European Economic Community (47). The Food and Agriculture Organization (FAO) of the United Nations (48) has certified their safe use in foods provided that no more than 200 ppm of free ionizable copper is present. Use of copper-containing chlorophyll derivatives in foods is not allowed in the United States under the Color Additive Amendment to the Food, Drug, and Cosmetic Act of 1938. 

Chlorophyll (E140) itself which exists as the compounds a and b (where the 3-methyl group in a has been replaced by a formyl substituent) is a less satisfactory colourant for commodity purposes than one of its derivatives lacking the phytyl group prepared by semi-synthesis (hydrolysis and coppering), namely copper chlorophyllin. 

Chlorophyll (E 140) exists as chlorophyll a (26) and chlorophyll b (27) and although it is not widely used as a coitimercial colourant, a derivative, copper chlorophyllin (29) is employed. 

For deriving copper chlorophyllin (E141), chlorophyll is hydrolysed under mild alkaline conditions and the product copperised to obtain the coordinated copper derivative. 

Two older reviews summarize work in this field [124,125]. The following derivatives have been employed as porphyrins Fe(II,III) protoporphyrin-EX (heme, hemin), Fe(II,III) or Co(II) protoporphyrin-IX-diester, chlorophyllins with different metal ions in the core, Fe(II) tetraphenylporphyrin, Mg(II) or Fe(II,III) octaethylporphyrin, Fe(II,III) tetrakis[o-(alkylamido)phenyl]-porphyrin. Polymers with N-donor groups are based on proteins such as poly(L-lysine), poly(L-histidine), poly(Y-benzyl-L-glutamate) or synthetic polymers such as homopolymers and copolymers with vinylpyridine, iV-vinylimidazole or ethyleneimine. 

Figure 11.14. Capacitance-potential curves for various concentrations of ZnTPPC (a) and Cu-chlorophyllin (b) at the water/DCE interface. The changes in the potential dependence of the capacitance, as well as the shift of the potential of minimum capacitance reflect the specific adsorption of the water-soluble porphyrin derivatives. Figure (a) reprinted with permission from ref.[95]. Copyright (2003) American Chemical Society. Figure (b) reproduced from ref.[87] by permission of the Royal Society of Chemistry.

This review has been limited, with a few exceptions, to low-molecular weight compounds with complement activity isolated from plants. Naturally occurring complement modulating compounds such as vitamin A, amino acids and derivatives, copper-chlorophyllin, etc., covered in previous reviews, e.g. by Asghar in 1984 [8], have not been included. 

The chlorophylls are methylphytol esters of the chlorophyllines, which are the corresponding acids. These are neutral substances containing magnesium in a non-ionic form. A hydrolase, called for this reason chloro-phyllase, splits off from chlorophylls a C-20 (with one double bond) aliphatic alcohol which is a diterpene derivative named phytol (see p. 31). 

Derivatives of chlorophyll a were found to be more effective radical quenchers than those of chlorophyll b. Furthermore, metal-lree derivatives such as chlorins, pheophytins, and pyropheopytins exhibited significantly lower antiradical capacity than metaUo-derivatives such as Mg-chlorophylls, Zn-pheophytins, Zn-pyropheo-phytins, Cu-pheophytin a, and Cu-chlorophyllins. It seems that dietary chlorophyll derivatives prevalent in both fresh and processed foods and dietary supplements have antioxidant and antimutagenic activities [60]. 

Currently, sodium-copper-chlorophyllin is the most widely used natural green colorant. This chlorophyll derivative has been the basis of many of the studies carried out on the functional value of chlorophyll compounds, and important antimutagenic and anticarcinogenic properties have been found. Research has been... 

ChlorophyUin copper complex is an isolate derived from natural sources. Unlike native plant chlorophyll, chlorophyllin copper complex is a water-soluble molecule. Water solubility is beheved to enhance the bioavailabihty of chlorophyll. The synthesis of chlorophyllin copper complex from native chlorophyll involves supplanting the magnesium atom at the center of the ring with copper. 

---