Porphyrin/corrole-coumarin Dyads: Synthesis, Photophysics And Anticancer Property

Porphyrins/corrroles and their metal complexes have attracted much attention in optical materials and biochemistry.In the last several decades,lots of tetrapyrrolic macrocycle derivatives have been prepared through the peripheral functionalization of meso/β-substituted tetrapyrrolic macrocycle cmplexes aimed to enhance the biological and photophysical properties.Coumarin is another group of biologically relevant heterocyclic compounds,which also possess interesting biological properties,such as anticancer,antimicrobial,and anti-inflammatory.It also displays good photophysical properties.Coumarin-tetrapyrrolic macrocycle conjugates have attracted much interests in the past years.They have potential uses in organic light-emitting diodes（OLEDs）,light harvesting,fluorescent probe and anti-cancer drugs.In this thesis,a series of corrole/porphyrin compounds with different substituents and their metal complexes are designed and synthesized.Futhermore,this is the first time to report the DNA interaction,photo-nuclease activity and in-vitro antitumor activity of porphyrin/corrole-coumarin dyads.The main research contents as follows:（1）A series of corroles（1³）10-（2-hydroxylphenyl）-5,15-Bis（pentafluorophenyl）Corrole,10-（3-hydroxylphenyl）-5,15-Bis（pentafluorophenyl）Corrole,10-（4-hydroxylphenyl）-5,15-Bis（pentafluorophenyl）Corrole and their gallium complexes（1-Ga³-Ga）has been synthesised.The single crystal structure of 2 was successfully obtained.Corroles exhibited good PDT activity towards tumor cells.After PDT treatment,corroles could induce the apoptosis in tumor cells which was collapse of the mitochondrial membrane potential and increase of the intracellular ROS level.（2）10-（4-Formylphenyl）-5,15-bis（pentafluorophenyl）corrole（4）and its gallium complex4-Ga were synthesized.4 and 4-Ga might pass across the tumor cell membrane smoothly without the help of carrier protein,and showed good PDT antitumor activity.After PDT treatment,the intracellular ROS level increased and the mitochondrial membrane potential decreased significantly,which would finally result in the apoptosis of tumor cells.（3）A new coumarin–corrole dyad（5）and its gallium complex（5-Ga）in which the coumarin unit is linked to the para-position of 10-phenyl group of the corrole were synthesized.Fluorescence emission of coumarin entity in all dyads were quenched significantly as compared to pristine coumarin,this was attributed to intramolecular energy transfer from coumarin to porphyrin.Photodynamic anti-tumor tests revealed gallium corrole-comarin dyad（5-Ga）exhibited good PDT activity towards SiHa cells.After PDT treatment,5-Ga could induce the apoptosis in SiHa cells which was associated to cell S phase arrest,collapse of the mitochondrial membrane potential and increase of the intracellular ROS level.（4）Three new non-conjugated porphyrin-coumarin dyads（9¹1）with different orientations with respect to donor-acceptor entities,and their zinc complexes had been synthesized.Single-crystal structures of free base porphyrin-coumarin dyads were successfully resolved.Absorption spectra indicating a negligible electronic communication between coumarin and porphyrin moiety.However,fluorescence emission indicating an intramolecular energy transfer from coumarin to porphyrin.Transient absorption studies showed the excited state decay process（S₂→S₁*,S₁*→S₁,S₁→S₀ and S₁→T₁）of para-isomer is faster than that of ortho-isomer in DMF.（5）Porphyrin-coumarin dyads were used to determine their interaction with ct-DNA,and photocleavage activity towards PBR322-DNA.The results revealed that all dyads interact with ct-DNA via an outside groove binding mode only,the binding constant was calculated as3.24×105（9）,3.05×10⁵（11）,3.04×10⁵（9-Zn）,4.88×10⁵（11-Zn）,and the photocleavage activity follows an order of 11-Zn<11<9-Zn<9.Furthermore,only the zinc porphyrin-coumarin dyads could be absorbed by tumor cells（A549）and were mainly localized in cytoplasm and showed red fluorescence,these zinc dyads showed low cytotoxicity towards all tested tumor cell lines,the results showed this zinc porphyrin-coumarin dyads have potential applications in fluorescence imaging.