Studies Of The Interaction Between Small Molecules And Biomolecules DNA

The dissertation can be divided into three parts:In the first part,a novel calix[4]arene derivative containing uracil,5-(Uracil-N¹ -acetamido)-25,26,27,28-tetrahydroxycalix[4]arene(UC),was designed and synthesized.Its interaction with nucleotides and bases has also been studied by ESI-MS andÏ€-A isotherms.The results of ESI-MS showed that UC could recognize adenine and adenosine from other nucleotides and bases.Meanwhile,Ï€-A isotherms at the air-water interface also indicated that there was interaction between UC and the species in the subphase,and the respective complexes were formed in the monolayer. The mean molecular area at zero surface pressure,which was the molecular area of the supramolecular complex,increased with the sizes of the nucleotides and bases in the subphase in the order:water2.In addition,the binding properties of UC with CT-DNA were investigated by UV-Vis spectroscopy and viscosity measurements.The results showed that UC can recognize DNA and bind to DNA via an intercalative mode,and a kind of supramolecular complex was formed where UC:DNA=1:1.Moreover,the cleavage of pBR322 DNA was studied by agarose gel electrophoresis.It indicated that UC can catalyze the cleavage of pBR322 DNA by H₂O₂ at 37℃,and pBR322 DNA was transformed from Formâ… (supercoil form)to Formâ…¡(open circular form).These results provide the theoretical and practical basis in the development of enzyme mimic regent containing calixarene for the site-specific cleavage of DNA.In the second part,a new ruthenium(â…¡)complex[Ru(tbz)₂(dppz)](ClO₄)₂(tbz= 2-(4'-thiazolyl)benzimidazole,dppz=dipyrido-[3,2-a:2',3'-c]phenazine)was synthesized and characterized by elemental analysis,electrospray mass spectra and ¹H NMR.The DNA binding properties of the complex with calf thymus DNA was investigated by spectroscopic and viscosity measurements.The results suggested that the complex binded to DNA via an intercalative mode.Moreover,the complex has been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm.The mechanism studies revealed that singlet oxygen ¹O₂ played a significant role in the photocleavage.In the third part,two new tridentate pyridine ligands and five new tridentate ruthenium(â…¡)terpyridine complexes[Ru(tpy)(L)](ClO₄)₂(L₁=2-(4-(2,6-di(pyridine -2-yl)pyridine-4-yl)phenyl)-1H-benzo[d]imidazole,L₂=2-(4-(2,6-di(pyridin-2-yl) pyridine-4-yl)phenyl)benzo[d]thiazole),L₃=4'-p-chlorophenyl-2,2':6',2"-terpyridine, L₄=4'-p-nitrophenyl-2,2':6',2"-terpyridine,L₅=4'-p-methoxylphenyl-2,2':6',2" -terpyridine),have been synthesized and characterized by elemental analysis, electrospray mass spectra and ¹HNMR.The DNA binding properties of the complexes with calf thymus DNA were investigated by absorption spectra,thermal denaturation,emission spectra and viscosity measurements,and the factors which influenced the binding affinity and binding mode such as steric hindrance and the polarity of the substituent groups and the electronic effects of intercalative ligands have been discussed in combination with the theoretical calculation.The results suggested that all of the three complexes could bind to DNA in an intercalative mode. And the binding affinity decreased in the order of 1＞2,3＞4＞5.Furthermore,the agarose gel electrophoresis experiments indicated that all of the five complexes could not cleavage pBR 322 DNA under irritation.Therefore,the complexes could be developed into new kinds of DNA structural probes which could bind to DNA without causing any damage.