Synthesis Of Naphthyridine Derivatives And Its Application In The Electrochemical Detection Of DNA

The 2-methyl-7-animo-1,8-naphthyridine is widely used in molecular recognition,Nakatani groups studies show that 2-methyl-7-animo-1,8-naphthyridine can stability interact with G base of nucleic acid by hydrogen bonding,and which can specifically recognit G base of nucleic acid.And a series of naphthyridine derivatives have been synthesized,which can be used for the identification of specific sequences of nucleic acid,a new kind of naphthyridine derivatives has been synthesized in our previous work,and which has been applied into the electrochemical sensor.And furthermore,the naphthyridine derivatives can detect and recognit CGG trinucleotide repeat sequences through electrochemical method,And it has achieved good results,naphthyridine derivatives NC can selectively identify GG mismatch double-stranded DNA,as well as the superiority of electrochemistry.In the paper,Take advantage of the selective interaction of the NC and GG mismatch DNA,Nucleic acid molecular is fixed on the electrode substrate surface,and a different kind of electrochemical sensor is established.Firstly,NC derivatives of amino terminal has been synthesized,in the middle of dsDNA,which is enough flexible long chain,and the naphthyridine derivatives can been fixed on the electrode through simple condensation reaction to set up a simple electrochemical sensor based on organic small molecules,The electrochemical sensor can be selectively capture GG mismatch dsDNA.Secondly,a label-free,rapid and simple method was proposed to recognit and detect G-G mismatch dsDNA using Hexaammineruthenium(?)chloride as a redox indicator.voltammetric signals of Ru(NH3)6]Cl3 were investigated at these modified electrodes by means of differential pulse voltammetry(DPV)detection.Differential pulse voltammetry signals of Ru(NH3)6]Cl3 indirect detect the ability of capture GG dsDNA by electrochemical sensor.The results show that the G-G mismatch dsDNA can be detected selectively by signals of Ru(NH3)6]Cl3 even in the presence of mixed other DNA and ct-DNA.G-G mismatch dsDNA can be easily discriminated from other mismatch dsDNA and complementary dsDNA based on the electrochemical sensor.Taken together,The linear relationship between electrochemical responses and DNA target concentration was also studied,which is from 10 nM to 4 ?M with detection limit down to 0.3 nmol/L.these experiments demonstrate that the hybridization indicator Ru(NH3)6]Cl3 provides great promise for rapid and specific measurement of target DNA.Thirdly,a simple electrochemical impedance spectroscopy(EIS)sensor was developed for highly sensitive and specific detection of target G-G mismatch dsDNA.After the electrochemical impedance sensor was incubated with G-G mismatch dsDNA,We found that the amount of DNA that were captured on the surface of the electrode is different,and it will hinder the electron transfer inordinately,and then lead to the change of impedance.After the electrochemical impedance sensor was incubated with G-G mismatch dsDNA,the results that the charge-transfer resistance(Rct)largely increased.Whereas the slight increased Rct values were only found for other mismatch dsDNA and complementary dsDNA.Importantly,the G-G mismatched dsDNA can be detected selectively based on the differences in charge transfer resistance(?Rct)even in the presence of mixed other DNA and ct-DNA.Under the optimal experimental conditions,the established EIS sensor could be used for the quantification of G-G mismatch dsDNA based on the linear relationship between ?Rct and lg[concentration of G-G mismatch dsDNA],which is from 1 nM to 1 ?M with detection limit down to 0.3 nmol/L.The sensing strategy might become a potential alternative tool for detection of G-G mismatch DNA in the diagnosis of the genetic diseases and early clinical diagnosis.Finally,The new trityl protection naphthyridine derivatives was designed and synthesized.It is hoped that NC-linker molecules of thiol end and thiol ferrocene were modified on the AuNPs.To establish an identification and recognition of GG mismatch DNA sequence AuNPs double functional electrochemical sensor.