Diimide reduction and reduction of tri- and tetrapyridylporphyrins with tin (II) chloride

Fotodinamička terapija (PDT) je jedan od suvremenijih pristupa u liječenju tumora te je još uvijek u razvoju. Za PDT su potrebne tri komponente: fotosenzibilizator (PS), izvor svjetlosti i molekularni kisik. Uspješnost PDT-a ovisi o svojstvima PS-a, a trenutno su najčešće korišteni tetrapirolni makrocikli: porfirini, klorini i bakterioklorini. Klorini i bakterioklorini imaju jači apsorpcijski pik u crvenom području (~ 650 - 750 nm) od porfirina (~ 630 nm) te ih upravo to fizikalno svojstvo čini boljim fotosenzibilizatorima zato što svjetlost te valne duljine (~ 650 - 750 nm) dublje prodire u tkivo. Cilj ovog diplomskog bio je ispitati metode dobivanja klorina iz tetra- i tripiridilporfirina te su napravljeni razni pokušaji modifikacije diimidne redukcije i redukcije s kositar(II) kloridom (SnCl2). Reakcije su rađene na tri različita porfirina: 5,10,15,20-tetrakis (3-piridil)porfirin (1), 5-(4-acetamidofenil)-10,15,20-tris(3-piridil) porfirin (2) i 5-(4-aminofenil)- 10,15,20-tris(3-piridil)porfirin (3). Dobiveni rezultati pokazali su da je redukcija porfirina s SnCl2 regioselektivna te u reakciji s porfirinom 2 daje gotovo isključivo klorin 9. U diimidnoj redukciji nastaje smjesa produkata (početni porfirin, klorin, bakterioklorin, izobakterioklorin) koju je teško odvojiti te se u ovom slučaju najbolje pokazala oksidacija produkata diimidne redukcije do klorina. Oksidacijom bakterioklorina 8 nastaje klorin 10 s primjesama nečistoća. U budućim ispitivanjima trebalo bi optimizirati metode odvajanja te bi se u redukciji s SnCl2 trebalo ispitati bi li nastalo više klorina kada bi se dodalo više ekvivalenata SnCl2.Photodynamic therapy (PDT) is one of the modern approaches in the treatment of tumors and is still in development. PDT requires three components: a photosensitizer (PS), a light source and molecular oxygen. The success of PDT depends on the properties of PS and currently the most commonly used PSs are tetrapyrrole macrocycles: porphyrins, chlorins and bacteriochlorins. Chlorins and bacteriochlorins have a stronger absorption peak in the red region (~ 650 - 750 nm) than porphyrins (~ 630 nm) and it is this physical property that makes them better photosensitizers because light of this wavelength (~ 650 - 750 nm) penetrates deeper into the tissue. The aim of this master thesis was to test the methods of obtaining chlorin from tetra- and tripyridylporphyrins and various attempts were made to modify the diimide reduction and reduction with tin (II) chloride (SnCl2). Reactions were performed on three different porphyrins: 5,10,15,20-tetrakis(3-pyridyl) porphyrin (1), 5-(4-acetamidophenyl)-10,15,20-tris(3-pyridyl) porphyrin (2) and 5-(4-aminophenyl)-10,15,20- tris(3-pyridyl) porphyrin (3). The obtained results showed that the reduction of porphyrin with SnCl2 is regioselective and in the reaction with porphyrin 2 gives almost exclusively chlorin 9. In diimide reduction a mixture of products is formed (initial porphyrin, chlorin, bacteriochlorin, isobacteriochlorin) which is difficult to separate and in this case it has been shown that oxidation of diimide reduction products to chlorin is the best option. Oxidation of bacteriochlorin 8 produces chlorin 10 with impurities. In future studies, separation methods should be optimized and, in reduction with SnCl2, it should be examined whether more chlorin would be formed when more SnCl2 equivalents are added