| Cancer has become a worldwide disease that creates serious threat to humanity health and life safety.Chemotherapy is an important treatment method but with obvious toxic effects.So to synthesize high efficient, broad-Spectrum,low toxic anticarcinogen and study their anticancer activity is becoming a strategic task of new drug development.Nowadays,the study on this topic is mostly concentrated on main group and transition metals, such as Platinum group anticarcinogen,metallocene anticarcinogen, organotin anticarcinogen and copper complex anticarcinogen,etc.Rare earthsions and their complexes as chemical nucleases are superior to transition metal and their complexes because they can bind to nucleic acid more efficiently by hydrogen bonding and hydrolyzed mode,as a result,it has gained prominence.Pyridinecarboxamide contains lipophilic group of pyridine,which can make the drugs more capable of penetrating through cell membrane to bind to the target DNA.More importantly,hydrophilic group of carboxamide can reduce toxicity brought by the drugs to the kidney.In this paper,we design and synthesize novel acylamide derivatives and their rare earth complexes.In order to screening high efficient,broad-Spectrum,low toxic anticancer drugs,design,synthesis and DNA-binding mode of novel acylamide derivatives and their rare earth complexes are discussed in this paper.We synthesized five novel N-substituted pyridinecarboxamide: N-phenyl-2-pyridinecarboxamide(L1),N-2-chlorine phenyl-2-pyridinecarboxamide(L2),N-2-nitro phenyl-2-pyridinecarboxamide(L3),N-pyridyl-2-pyridinecarboxamide(L4),N, N'-bis(2-pyridine carboxamide)-1,4-diethylenetriamine(L5).They were characterized by NMR spectrum,IR spectrum and elemental analysis.The interaction between the compounds and DNA was studied by means of UV-visible spectra,fluorescence spectra,surface enhanced raman spectroscopic,viscometric titration and agarose gel electrophoresis.The results showed that compounds can bind to DNA in different degree.The binding ability followed the trend from high to low:L3,L1,L4,L2 and L5. Because the molecules of L1,L2,L3 and L4 have the advantage of small size and appropriate planarity,they are easy to insert their aromatic ring to the base pairs of DNA.The acylamide groups of two terminal in L5 have the advantage of hydrophilicity,and the middle long fatly chain in L5 is of good flexibility.So the interaction modes between DNA and L5 are mainly in groove binding.In conclusion,appropriate planarity and lesser steric hindrance make the ligands prone to insert their aromatic ring to the base pairs of DNA.The introduction of absorbing electronic group in aromatic ring will go against coupling effect between the ligands' aromatic ring and DNA,Which will decreased the pharmacodynamic effect.On the contrary, the introduction of electron-donating groups will enhance the effectiveness of medicine.Then we synthesized twelve rare earth complexes containing ligand of N-phenyl-2-pyridinecarboxamide.The results of elemental analysis, conductivity measurement,IR spectra and thermal analysis confirmed their chemical composition were:[Ln(L1)3(H2O)2](NO3)3·2H2O,Ln=La(Ⅲ)and Ce(Ⅲ);[Ln(L1)2(H2O)(NO3)](NO3)2·3H2O,Ln=Nd(Ⅲ),Sm(Ⅲ),Eu(Ⅲ), Gd(Ⅲ),Dy(Ⅲ),Ho(Ⅲ),Er(Ⅲ),Tm(Ⅲ),Yb(Ⅲ)and Lu(Ⅲ).To make convenient discussion,the twelve rare earth complexes could be divided into three series.La(Ⅲ)series contained La(Ⅲ)and Ce(Ⅲ)complexes;Eu(Ⅲ) series were Sm(Ⅲ),Eu(Ⅲ),Gd(Ⅲ)and Dy(Ⅲ)complexes;Ho(Ⅲ)series were Ho(Ⅲ),Er(Ⅲ),Tm(Ⅲ),Yb(Ⅲ)and Lu(Ⅲ)complexes.The interaction between the three series and DNA was studied by means of UV-visible spectra,fluorescence spectra,SERS spectra,viscometric titration,agarose gel electrophoresis and atomic force microscopy.The results showed that all complexes can bind to DNA strongly.The binding ability of the three series followed the trend from high to low:Eu(Ⅲ)series,La(Ⅲ)series and Ho(Ⅲ) series.Series complexes bound to DNA probably by inserting their L1 molecule to the base pairs of DNA.Series complexes bound to DNA stronger than free L1.The results are probably attributed to the extension of theπsystem of the intercalated ligand due to the coordination of Ln(Ⅲ),which also leads to a planar area greater than that of the free ligand,which leads to the coordinated ligand penetrating more deeply into,and stacking more strongly with the base pairs of the DNA.In addition,we synthesized and characterized eleven rare earth complexes containing ligand of N,N'-bis(2-pyridinecarboxamide)-1, 4-diethylenetriamine.The results of elemental analysis,conductivity measurement,IR spectra,thermal analysis and NMR spectrum confirmed their chemical composition were:[La(H3L5)(NO3)2]NO3Cl3·3H2O,Ln= La(Ⅲ),Nd(Ⅲ),Sm(Ⅲ),Eu(Ⅲ),Gd(Ⅲ),Dy(Ⅲ),Ho(Ⅲ),Er(Ⅲ),Tm(Ⅲ), Yb(Ⅲ)and Lu(Ⅲ).And also,the interaction between series complexes and DNA was studied by means of UV-visible spectra,fluorescence spectra, SERS spectra and viscometric titration.From the results,there were not evident insertion action between series complexes and DNA.Their interaction modes were probably in groove binding and electrostatic effect.
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