[8π+2π] Cycloaddition of meso‐Tetra‐ and 5,15‐Diarylporphyrins: Synthesis and Photophysical Characterization of Stable Chlorins and Bacteriochlorins

Abstract

The synthesis of new types of stable 4,5,6,7‐tetrahydropyrazolo[1,5‐a]pyridine‐fused chlorins and bacteriorins through [8π+2π] cycloaddition of diazafulvenium methides with porphyrins and chlorins is reported. Detailed absorption and fluorescence spectral and quantum yield measurements have been made on all new compounds. These show potential for various biomedical applications.

Ring-Fused meso-Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation

“…Ring-fused chlorins 4 were obtained via [8π + 2π] cycloaddition of diazafulvenium methide 2 , formed in situ from sulfur dioxide extrusion of sulfone 1 under microwave irradiation, with porphyrins 3 according to the procedure previously developed by our group ( Pereira et al, 2010 ; Pereira et al, 2011 ). In order to further explore structure-activity relationships, we decided to expand the study to other derivatives having different amphiphilic properties.…”

“…Chlorins 4 ( Pereira et al, 2010 ; Pereira et al, 2011 ) were prepared from the reaction of 2,2-dioxo-1 H ,3 H -pyrazolo[1,5- c ][1,3]thiazole-6,7-dicarboxylate 1 ( Sutcliffe et al, 2000 ; Sutcliffe et al, 2001 ) and meso -tetraarylporphyrin 3 ( Liu et al, 2009 ) under microwave irradiation at 250°C for 20 min, as previously described.…”

“…Yet, these derivatizations usually yield tetrahydroporphyrins (bacteriochlorins and/or isobacteriochlorins) as unwanted side-products, which complicates the isolation and purification procedures of the target chlorin. As we have previously demonstrated, the stability of chlorins can be greatly enhanced with the simple introduction of a fused ring via [8π + 2π] cycloaddition reactions ( Pereira et al, 2010 ; Pereira et al, 2011 ). In fact, it was shown that porphyrins react with in situ generated diazafulvenium methides to deliver a new type of stable 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyridine-fused chlorins with favorable photophysical features regarding PDT.…”

Ring-Fused Diphenylchlorins as Potent Photosensitizers for Photodynamic Therapy Applications: In Vitro Tumor Cell Biology and in Vivo Chick Embryo Chorioallantoic Membrane Studies

“…The reduction of these diester chlorins ( 1 and 2 ) with lithium aluminum hydride led to the corresponding dihydroxymethyl chlorins ( 3 and 4 ). 37,40 Chlorins 1 – 4 present photophysical properties that are adequate to their use as photosensitizers with high absorption at the therapeutic window and moderate to high singlet oxygen quantum yields.…”

“…Our contribution overcame this with the development of a new class of highly stable ring-fused chlorins. Novel 4,5,6,7-tetrahydropyrazolo­[1,5- a ]­pyridine-fused chlorins were synthesized via [8π + 2π] cycloaddition of transient 1,7-dipole diazafulvenium methides with porphyrins. , Further studies demonstrated that this kind of ring-fused meso -tetraphenylchlorins, particularly a new dihydroxymethyl derivative, has an impressive performance against human skin malignant melanoma . Furthermore, the incorporation of the platinum­(II) metal into their structure originated excellent theranostic agents for imaging, PDT, and molecular oxygen sensing …”