Synthesis, G-quadruplexes DNA binding, and photocytotoxicity of novel cationic expanded porphyrins

• Novel extended cationic porphyrins were successfully designed and synthesized.
• Positive substituents play the most important roles in G4-DNA binding.
• These extended porphyrins could serve as photochemotherapeutic agents.

Intensive reports allowed the conclusion that molecules with extended aromatic surfaces always do good jobs in the DNA interactions. Inspired by the previous successful researches, herein, we designed a series of cationic porphyrins with expanded planar substituents, and evaluated their binding behaviors to G-quadruplex DNA using the combination of surface-enhanced raman, circular dichroism, absorption spectroscopy and fluorescence resonance energy transfer melting assays. Asymmetrical tetracationic porphyrin with one phenyl-4-N-methyl-4-pyridyl group and three N-methyl-4-pyridyl groups exhibit the best G4-DNA binding affinities among all the designed compounds, suggesting that the bulk of the substituents should be matched to the width of the grooves they putatively lie in. Theoretical calculations applying the density functional theory have been carried out and explain the binding properties of these porphyrins reasonably. Meanwhile, these porphyrins were proved to be potential photochemotherapeutic agents since they have photocytotoxic activities against both myeloma cell (Ag8.653) and gliomas cell (U251) lines.

The newly synthesized extended porphyrin with one phenyl-pyridyl group and three N-pyridinium groups exhibit even higher G4-DNA binding affinities than TMPyP4 though FERT melting experiment, suggesting that the bulk of the substituents may match the width of the grooves they putatively lie in.Figure optionsDownload as PowerPoint slide