Synthesis, Spectral Properties And Photocleavage DNA Activities Of Corroles And Phenothiazine-corrole Dyads

Macrocyclic compounds which could bind and cleave nucleic acids are of current interest for their importance as reagents to retrieve structural and genetic information of DNA and to develop efficient chemical nucleases. Corrole is an 18-p electron macrocycle having a direct pyrrole-pyrrole linkage. Its ring structure is in close resemblance to porphyrin. As a PDT photosensitizer, Corrole has the advantages of having more intense absorption of visible light, larger Stokes shift and less robust during metabolism as compared to porphyrin. It is well known that porphyrin photosensitizer might be localized in tumor cell, and caused tumor cell damage under irradiation. The porphyrin mediated DNA photo-cleavage has well been documented in the past years. However, less attention has been paid to the DNA photocleavage by Corrole derivatives so far. A large number of novel synthesis and function of Corroles waiting for people to open up. On the basis of careful investigation of the most recent references, we have designed and synthesized a series of Corrole and Corrole-phenothiazine dyads, and have studied their spectral properties,DNA binding and DNA photocleavage activities.Firstly, a series of mono-hydroxyl Corroles bearing fluorin, chlorine, bromine and iodine atoms on its 10-phenyl group was synthesized. Steady state and time-resolved fluorescence spectra measurement show that the halogen atoms on the meso- phenyl group exhibit significant heavy atom effect on their photophysical property. The fluorescence quantum yield and the lifetime of these Corroles decrease with the increasing of atomic weight of halogen atom. These may be understood by the increasing Kisc caused by the heavy atom effect of halogen atoms. From the heavy atom effect of view, Corrole bearing iodine atom present the lowest fluorescence quantum yield (0.040) and the highest intersystem crossing rate constant (388.28′10-3 ns-1). DNA photocleavage properties of these halogenated mono-hydroxyl Corroles were also investigated. It was found that these Corroles were able to cleave supercoiled pBR 322 DNA (Form I) into nicked-circular DNA (Form II). The DNA photocleavage activity increase with the increasing of atomic weight of halogen atom. The photosensitized singlet oxygen (Ф_△) quantum yield by these Corroles also follows that same order, showing the photocleavage activity is related to the heavy atom effect of halogen atoms on Corroles. This work will be helpful in giving insight into the PDT activity of halogenated Corroles.Secondly, a series of mono-hydroxyl Corroles and Corrole-phenothiazine dyads was successfully synthesized. The Corrole-phenothiazine dyads could be efficiently prepared at room temperature in the presence of DBU with yields of 60-95%. The Corrole-phenothiazine dyads exhibit higher fluorescence quantum yield and longer singlet exited lifetime than their parent mono-hydroxyl Corroles. The enhanced fluorescence quantum yield and lifetime may be caused by the introduction of phenothiazine unit, which is known as an excellent building block for impeding aggregation and intermolecular excimer formation. As compared to Corrole monomer, these Corrole-phenothiazine dyads exhibit significant enhanced DNA photocleavage activity,higher singlet oxygen quantum yields and DNA binding activities.Thirdly, three Corrole-phenothiazine Gallium (III) complexes have been synthesized. The steady-state absorption and emission spectra and the time-resolved fuorescence decay profiles have been measured in toluene and the radiative and nonradiative rate constants have been obtained from the fluorescence quantum yields and monoexponential fluorescence lifetimes. The absorption spectra reveal that the Corrole unit of the Gallium (III) dyad exhibit stronger Soret band and Q band. The fuorescence quantum yields of these Gallium (III) Corrole complexes are 0.502, 0.443 and 0.494, and the radiative rate constans are 20.9′107 s-1, 16.78′107 s-1 and 21.11′107 s-1, which are obviously higher than their free base Corroles, wheras the lifetime were somewhat shorter. Agarose gel electrophoresis shows that these Gallium (III) Corroles could also cleave supercoiled DNA (Form I) to nicked-circular DNA (Form III ) under irradiation.Finally, mono-hydroxyl Corrole copper (III) and Corrole-phenothiazine copper (III) complexes have been synthesized. These two copper (III) Corrole complexes could proteCT DNA against the damage of H2O2, and the Corrole-phenothiazine copper (III) complex exhibit improved activities. This kind of information is crucial for the design of an optimal catalyst for the dismutation of superoxide。...