Interaction and photodynamic activity of cationic porphyrin derivatives bearing different patterns of charge distribution with GMP and DNA

Abstract

The interaction of amphiphilic cationic porphyrins, containing different patterns of meso-substitution by 4-(3-N,N,N-trimethylammoniumpropoxy)phenyl (A) and 4-(trifluoromethyl)phenyl (B) groups, with guanosine 5′-monophosphate (GMP) and calf thymus DNA have been studied by optical methods in phosphate buffer solution. The properties of these synthetic porphyrins were compared with those of representative standard of anionic 5,10,15,20-tetra(4-sulphonatophenyl)porphyrin (TPPS44−) and cationic 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin (TMAP4+). Stable complexes with GMP were found for cationic porphyrins, except for monocationic AB3+. The binding constant (KGMP ∼ 104 M−1) follows the order: A3B3+ ∼ ABAB2+ > A44+ ∼ TMAP4+. Also, interaction with DNA was observed for all evaluated cationic porphyrins. For these related cationic porphyrins, the binding constant (KDNA ∼ 105 M−1) increases with the number of cationic charges. On the other hand, the photodynamic activity of porphyrins was analyzed in solution of GMP and DNA. Monocationic AB3+ is a less effective sensitizer to oxidize GMP in comparison with the other cationic porphyrins, in agreement with the lack of detected interaction with this nucleotide. The electrophoretic analysis of DNA indicates that photocleavage takes place when the samples are exposed to photoexcited tricationic and tetracationic porphyrins. In the presence of sodium azide the DNA decomposition was diminished. Also, reduction in the DNA photocleavage was observed under anoxic condition, indicating that oxygen is essential for DNA photocleavage sensitized by these cationic porphyrins. In addition, an increase in DNA degradation was not observed in deuteriated water. Therefore, an important contribution of type I photoreaction processes could be occurring in the DNA photodamage sensitized by these cationic porphyrins. These results provide a better understanding of the characteristics needed for sensitizers to produce efficient DNA photocleavage.