Water Soluble Cationic Porphyrins With Different Self-aggregation Tendencies Showing Different PH-dependent G-quadruplex Recognition Behaviors

Besides canonical Watson-Crick B-form helix,DNA can also exist in variety of non-canonical secondary structures.A well-known one is G-quadruplex.G-quadruplexes have attracted significant attention due to their increasingly discovered biological importance,mainly as possible regulators of gene transcription in promoter regions of oncogenes and telomeric regions.Studies have shown that some small molecular drugs can be used as ligands of G-quadruplex.However,as unique identification of G-quadruplex of ligands are rarely reported in the physiological pH range.So,it is much more important to searching the unique identification of G-quadruplex of ligands.Porphyrin derivatives have attracted particular attention since their size,shape and hydrophily are quite similar to G-quadruplex structure,and their intrinsic colorimetric and fluorescent properties can provide convenient handle on monitoring their interactions with DNAs.These findings suggest that elongation of the alkyl substituent to porphyrin side arm and modify the kind of substituent,are possibly the important influencing factors for biological characteristics.Therefore,in this article,two cationic porphyrins derivatives with elongation of the alkyl substituent were designed and their recognition ability for G-quadruplex in the physiological pH range were studied.In this paper,the research content is divided into the following three parts:1.Two new cationic porphyrin derivatives,5,10,15,20–tetrakis{4–[2–(3-Nmethylpyridyl)ethoxy]phenoxy}porphyrin(m-TMPyEOPP)and 5-[4-(ethenyloxy)phenly],10,15,20-tri{4–[2–(3-N-methylpyridyl)ethoxy]phenoxy} porphyrin(TriMPyE(V)OPP)have been designed and synthesized.The conditions of the synthesis and purifications of these compounds are explored in the thesis and the structures of the two porphyrins are characterized by IR,NMR and MS,etc.2.The self-aggregation behavior and recognition ability to single,double chain and G-quadruplex DNA of m-TMPyEOPP has been studied via UV and fluorescence spectra in pH = 5.0-8.0 range,comparing with TMPyP4 and TMPipEOPP reported previously.The result shows that m-TMPyEOPP can recognize G-quadruplex in a wide pH physiological range of 5.0-7.5.The type and length of the side arm chain in porphyrins put an important effect on their biological properties.3.The recognition ability of TriMPyE(V)OPP to G-quadruplex has been preliminarily studied by UV and fluorescence spectra,and the effect of the numbers of substituents on its biological property has been discussed.