Click approach for the synthesis of 1,4-disubstituted-1,2, 3-triazoles of porphyrin-isatin/sulfa drug conjugates based on m-THPP

Abstract

New porphyrin-isatin/sulfa drugs conjugates based on symmetrical 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin ([Formula: see text]-THPP) with 1,4-regioisomers of 1,2,3-triazole linker were successfully synthesized. The constructed porphyrin-conjugates 15-19 and 22-24 contained mono-, tri- (unsymmetrical), or tetrafunctionalized units of isatin, sulfanilamide and sulfapyridine with 1,2,3-triazole linker. The synthesis of these conjugates was achieved by nucleophilic functionalization of [Formula: see text]-THPP by propargyl bromide followed by zinc metalation to achieve the mono-/tri-/tetrafunctionalized propargyl[Formula: see text]-THPP zinc-complex derivatives 3-5 (alkyne partners). The formed alkyne partners underwent cycloaddition reaction with isatin azide 8, azidosulfanilamide 13 and azidosulfapyridine 14 (azide partners) using click conditions via applying copper (I) catalyzed azide-alkyne cycloaddition (CuAAC). The utilized protocol succeeded in generating amphiphilic conjugates based on [Formula: see text]-THPP in an easy, simple, and quick manner, with high regioselectivity and high yields for potential medicinal and biological applications. The Zn-porphyrin derivatives’ photonic properties were investigated via photoabsorption and fluorescence. The optical properties were also studied and it is obvious that the Zn-porphyrin complex derivatives are different from those of the free-base porphyrin and could be relied on the number of triazole units and bioconjugate type.