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The Synthesis of the Dimethyl Ester of Quino[4,4a,5,6-efg]-Annulated 7-Demethyl-8-deethylmesoporphyrin and Three of Its Isomers with Unprecedented peri-Condensed Quinoline Porphyrin Structures. Molecules with Outstanding Properties as Sensitizers for Photodynamic Therapy in the Far-Red Region of the Visible Spectrum
The mesoporphyrin dimethyl ester nickel complex has been formylated via the Vilsmeier method. The four possible mono meso‐formyl derivatives were isolated and characterized. Wadsworth−Emmons coupling with the anion of (diethylphosphono)acetonitrile converted these aldehydes into the four novel meso...
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| Published in: | European journal of organic chemistry 2004-10, Vol.2004 (19), p.4024-4038 |
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| Main Authors: | , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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| Summary: | The mesoporphyrin dimethyl ester nickel complex has been formylated via the Vilsmeier method. The four possible mono meso‐formyl derivatives were isolated and characterized. Wadsworth−Emmons coupling with the anion of (diethylphosphono)acetonitrile converted these aldehydes into the four novel meso acrylonitriles. Brief treatment of these acrylonitrile systems in hot trichloroacetic acid resulted in the formation of four achiral porphyrin derivatives with unprecedented nickel complexes of quino‐fused porphyrins. Subsequent removal of the nickel gave four quino‐porphyrin free bases: quino[4,4a,5,6‐efg]‐annulated 7‐demethyl‐8‐deethylmesoporphyrin dimethyl ester 6a, 2′‐(methoxycarbonyl)quino[4,4a,5,6‐jkl]‐annulated 12‐demethyl‐13‐de[2′‐(methoxycarbonyl)ethyl]mesoporphyrin dimethyl ester 6b, 2′‐(methoxycarbonyl)quino[4,4a,5,6‐qrs]‐annulated 18‐demethyl‐17‐de(2′‐methoxycarbonylethyl)mesoporphyrin dimethyl ester 6c and quino[4,5,6,7‐abt]‐annulated 2‐demethyl‐3‐deethylmesoporphyrin dimethyl ester 6d. The structures of these systems were unambiguously determined via mass spectroscopy and a plethora of NMR techniques. In the same way, etioporphyrin and octaethylporphyrin were converted into the corresponding peri‐condensed quinoporphyrins as products, which shows that the formation of novel pericondensed quino‐porphyrins is a general reaction in the porphyrin series and will have a wide scope in this field. Also, a plausible reaction mechanism for the formation of the quinoporphyrin systems was derived. As a first test for the use of these systems as sensitizers in far‐red phototherapy, the quantum yield of singlet oxygen generation by 6a in toluene was studied. This quantum yield is 0.77, which is even higher than the singlet oxygen generation by sensitized meso‐tetraphenylporphyrin. Secondly, when Chinese Hamster ovary (CHO) cells were incubated in medium which contained up to 15 μg/ml of 6a, the survival rate of the cells in the dark is complete within experimental error, showing that under these conditions, 6a is not toxic to CHO cells. When CHO cells incubated in medium containing 6a in concentrations of 1 μg/ml and higher were treated with white light of intensity 30 mW/cm2 for 15 minutes, complete cell death was observed. Based on these facts, we expect that all four achiral systems will show very promising properties to form the basis of a photodynamic therapy in far‐red light. The fact that these systems are achiral is an additional bonus for medical appli |
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| ISSN: | 1434-193X 1099-0690 |
| DOI: | 10.1002/ejoc.200400366 |