Chlorins Designed for Photodynamic Tumor Therapy and as Model Systems for Photosynthesis

Abstract

Chlorophyll a (l), the green photosynthesis pigment, is the prototype of the chlorin class of natural products,"] which has recently been expanded to include a number of compounds ['] with differing structures, biological sources, and functions. The common structural unit in this class is the chlorin framework 2 with a partially saturated pyrrole ring, which is derived from the completely unsaturated porphyrin. The photophysical properties of the chlorins resulting from this structural modification predestine them as pigments for photosynthesisr3] and for medical applications, for example in photodynamic tumor therapy (PDT).14]The chlorin r a~-3 [~] with geminal dialkyl substitution in the saturated pyrrole ring was easily obtained from the red blood pigment heme and functionalized in the 3 position by degradation of the double bond. Artifical photosynthesis systems may thus be prepared containing "natural" chlorins as the structural units in contrast to the previously synthesized model systems based on porphyrins. The functionalized chlorin rue-8 may be modified to provide sensitizer structures and fluorescence markersr6] for photodynamic tumor therapy and other diagnostic/therapeutic applications.Chlorin rac-3 was first complexed with zinc(1r) ions to protect the chromophore (Scheme 1). The oxidative cleavage of the exocyclic double bond and subsequent decomplexation under acidic conditions led to oxochlorin rac-7. The amide function in vac-6 was hydrolyzed readily due to the anchimeric participation of the 3-0x0 group to give rue-14. The preparation of the corresponding nickeloxochlorin rac-11 required the hydrolysis of the amide function and cleavage of the double bond by iodolactonization, followed by a retro-aldol-type fragmentation and oxidation with MnO,.r7] The X-ray structure analysis[81 of the nickeloxochlorin rac-11, which was conducted in light of the coenzyme function of metal-containing chlorins, [*g. k1

Synthetic Chlorins, Possible Surrogates for Chlorophylls, Prepared by Derivatization of Porphyrins

“…A great deal, perhaps the majority, of semisynthesis of chlorins begins with chlorophylls, thereby retaining the dihydroporphyrin chromophore throughout the synthesis. A complementary approach entails transformation of hemin to a gem-dialkylchlorin, which was pioneered by Montforts. ,− It almost goes without saying that chlorophylls and hemin are vastly abundant compounds. Note that heme is the Fe­(II) chelate of protoporphyrin IX whereas hemin is the Cl–Fe­(III) chelate thereof.…”

“…The syntheses began with the chlorins 7-H 2 5a­( E/Z ) derived from the “2-isomer” of acetyl-deuteroporphyrin IX dimethyl ester (Scheme ). , The mixture of E/Z isomers, obtained as shown in Scheme , was metalated with nickel acetylacetonate to give the nickel chelates 7-Ni5a­( E/Z ). Treatment of the latter to a series of reactions resulted in the oxochlorin 7-Ni16 where also the amide was converted to an ester.…”

Porphycenes: Facts and Prospects in Photodynamic Therapy of Cancer

“…40 kJ·mol -1 [95], ground-state absorption should be below 900 nm. Likewise, higher absorption intensities can also be achieved by aza substitution in the macrocycle skeleton and by symmetry reduction (or breaking), thereby lifting the prohibition on the absorption transitions [62,[99][100][101]. A heavy atom effect in PS metallo-complexes increases triplet formation quantum yield.…”

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…Initial work on porphyrin conjugates focused on steroids [68,69] . For example, the first investigation was aimed at studying the effect of steroid hormones such as estrone and progesterone for targeting an excess of receptors in breast cancer cells [70] . A typical example is the synthesis of an estrone derivative 2 covalently linked through an alkenyl unit via a Heck type reaction with a meso-iododiphenylporphyrin 1 (Scheme 1) [71] .…”