含氮芳香化合物的合成、表征及与DNA作用机理的电化学研究
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摘要
本论文合成了7种含氮化合物，用元素分析、红外光谱以及X-射线衍射分析测定了其晶体结构。选择三个具有电化学活性的金属配合物Cu(C_(16)H_(14)N_2O_2)、[Co(bth)_2(H_2O)_4]ClO_4及[Cd(C_7H_6N_2)_2](NO_3)_2，利用电化学方法研究了它们与DNA的作用机理，确定了最佳反应条件。运用核酸杂交技术，用[Co(bth)_2(H_2O)_4]ClO_4及[Cd(C_7H_6N_2)_2](NO_3)_2作为指示剂制备了DNA电化学传感器。
本论文共分为六章：
第一章概述了杂坏化合物的分类、应用及研究进展，尤其苯并含氮杂环化合物、噻哗类化合物和咪唑类化合物的研究和应用。综述了杂环化合物与DNA作用的机理、DNA电化学传感器的设计原理及杂交指示剂的研究，重点介绍了DNA电化学传感器研究的现状及发展趋势。
第二章以邻苯二胺为原料合成了酰胺、苯并噻二唑、苯并咪唑等7种含氮化合物及配合物，并采用元素分析、红外、核磁和单晶X射线衍射分析确定了它们的结构。
第三章运用循环伏安法及微分脉冲伏安法研究了Cu(C_(16)H_(14)N_2O_2)与鲑鱼精DNA的相互作用。Cu(C_(16)H_(14)N_2O_2)在玻碳电极上的循环伏安图出现一氧化峰，当其与DNA作用后，氧化峰电流减小，氧化峰电位几乎不发生变化。结果表明，Cu(C_(16)H_(14)N_2O_2)与DNA结合比为2：1，结合常数为6．63×10~5L~2·mol~(-2)。
第四章运用循环伏安法及微分脉冲伏安法研究了[Co(bth)~2(H_2O)_4]~+在0．2mol·L~(-1)的AcOH-AcONa缓冲溶液中与鲑鱼精DNA的相互作用，结果表明[Co(bth)_2(H_2O)_4]~+通过嵌插作用与DNA结合。以[Co(bth)_2(H_2O)_4]~+为杂交指示剂，通过共价键合法进一步制备成DNA生物传感器。测定了DNA电化学传感器检测人免疫缺陷病毒(HIV)的检测线性范围为3．2×10~(-7)-2．9×10~(-6)mol·L~(-1)，在此浓度范围内的DNA可定量检测；检测限为1．1×10~(-7)mol·L~(-1)(S／N=3)。
第五章运用循环伏安法及微分脉冲伏安法研究了在0．2 mol·L~(-1)的AcOH-AcONa缓冲溶液中，[Cd(C_7H_6N_2)_2]~(2+)与鲑鱼精DNA的相互作用，结果表明[Cd(C_7H_6N_2)_2]~(2+)通过嵌插作用与DNA结合。以[Cd(C_7H_6N_2)_2]~(2+)为杂交指示剂，通过共价键合法进一步制备成DNA生物传感器。测定了DNA电化学传感器检测乙肝病毒(HBV)的检测线性范围为1．49×10~(-7)～1．06×10~(-6)mol·L~(-1)，检测限为8．4×10~(-8)mol·L~(-1)(S／N=3)。
第六章为结论部分，对全文内容进行了总结。
In this paper, seven iV-containing compounds were synthesized and characterized by elemental analysis, IR spectra, ~1H NMR and X-ray crystallographic analysis. N-containing compounds coordinated with transitional metal were synthesized and the electrochemical nature and the interaction with DNA were investigated.
In the first chapter, the classification of heterocyclic compounds, application and research progress, especially benzoic-nitrogenous heterocyclic compounds, thiazole compounds and the research and application of imidazole compounds were introduced.
In the second chapter, with o-diaminobenzene as the original material, five series of compounds, such as amide, benzothiobiazole and benzimidazole derivatives, were synthesized. The compounds were coordinated with metals to form metal complexes. The compounds were characterized by elemental analysis, IR spectra and ~1H NMR. Five single crystals of them were obtained and their structures were determined by X-ray crystallography method.
In the third chapter, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Cu(C_(16)H_(14)N_2O_2)] and salmon sperm DNA. When DNA was added, the peak current of [Cu(C_(16)H_(14)N_2O_2)] was decreased and the peak potential was not changed. In 0.2 mol·L~(-1) B-R buffer solution, the binding ratio between [Cu(C_(16)H_(14)N_2O_2)] and salmon sperm DNA was calculated to be 2:1 and the binding constant was 6.63×10~5 L~2·mol~(-2).
In the fourth chapter, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Co(bth)_2(H_2O)_4]~+ and salmon sperm DNA. An electrochemical DNA biosensor for the detection of short DNA sequence related to the human immunodeficiency virus (HIV) was developed with [Co(bth)_2(H_2O)_4]~+ as hybridization indicator. With this approach, a sequence of the HIV could be quantified over the range from 3.2×10~(-7) mol·L~(-1) to 2.9×10~(-6) mol·L~(-1), with a detection limit of 1.1×10~(-7) mol·L~(-1). The electrochemical sensor showed good selectivity.
In the fifth chapter, the process of [Cd(C_7H_6N_2)_2]~(2+) on glassy carbon electrode might be a quasi-reversible reaction controlled neither by adsorption nor by diffusion. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Cd(C_7H_6N_2)_2]~(2+) and salmon sperm DNA. The results show that the mode of the interaction of DNA with [Cd(C_7H_6N_2)_2]~(2+) is intercalative. The novel hybridization indicator, bis(benzimidazole)cadmium(II) dinitrate (Cd(bzim)_2(NO_3)_2), was utilized to develop an electrochemical DNA biosensor for the detection of short DNA sequence related to the hepatitis B virus (HBV). With this approach, a sequence of the HBV could be quantified over the range from 1.49×10~(-7) mol·L~(-1) to 1.06×10~(-6) mol·L~(-1), with a linear correlation of r = 0.9973 and a detection limit of 8.4×10~(-8) mol·L~(-1). The [Cd(C_7H_6N_2)_2]~(2+) signal observed from probe sequence before and after hybridization with four bases mismatch containing sequence was lower than that observed after hybridization with complementary sequence, showing good selectivity. These results demonstrate that the indicator [Cd(C_7H_6N_2)_2]~(2+) provides great promise for rapid and specific measurement of target DNA.In the last chapter, it was summarized for the whole thesis.
本论文共分为六章：
第一章概述了杂坏化合物的分类、应用及研究进展，尤其苯并含氮杂环化合物、噻哗类化合物和咪唑类化合物的研究和应用。综述了杂环化合物与DNA作用的机理、DNA电化学传感器的设计原理及杂交指示剂的研究，重点介绍了DNA电化学传感器研究的现状及发展趋势。
第二章以邻苯二胺为原料合成了酰胺、苯并噻二唑、苯并咪唑等7种含氮化合物及配合物，并采用元素分析、红外、核磁和单晶X射线衍射分析确定了它们的结构。
第三章运用循环伏安法及微分脉冲伏安法研究了Cu(C_(16)H_(14)N_2O_2)与鲑鱼精DNA的相互作用。Cu(C_(16)H_(14)N_2O_2)在玻碳电极上的循环伏安图出现一氧化峰，当其与DNA作用后，氧化峰电流减小，氧化峰电位几乎不发生变化。结果表明，Cu(C_(16)H_(14)N_2O_2)与DNA结合比为2：1，结合常数为6．63×10~5L~2·mol~(-2)。
第四章运用循环伏安法及微分脉冲伏安法研究了[Co(bth)~2(H_2O)_4]~+在0．2mol·L~(-1)的AcOH-AcONa缓冲溶液中与鲑鱼精DNA的相互作用，结果表明[Co(bth)_2(H_2O)_4]~+通过嵌插作用与DNA结合。以[Co(bth)_2(H_2O)_4]~+为杂交指示剂，通过共价键合法进一步制备成DNA生物传感器。测定了DNA电化学传感器检测人免疫缺陷病毒(HIV)的检测线性范围为3．2×10~(-7)-2．9×10~(-6)mol·L~(-1)，在此浓度范围内的DNA可定量检测；检测限为1．1×10~(-7)mol·L~(-1)(S／N=3)。
第五章运用循环伏安法及微分脉冲伏安法研究了在0．2 mol·L~(-1)的AcOH-AcONa缓冲溶液中，[Cd(C_7H_6N_2)_2]~(2+)与鲑鱼精DNA的相互作用，结果表明[Cd(C_7H_6N_2)_2]~(2+)通过嵌插作用与DNA结合。以[Cd(C_7H_6N_2)_2]~(2+)为杂交指示剂，通过共价键合法进一步制备成DNA生物传感器。测定了DNA电化学传感器检测乙肝病毒(HBV)的检测线性范围为1．49×10~(-7)～1．06×10~(-6)mol·L~(-1)，检测限为8．4×10~(-8)mol·L~(-1)(S／N=3)。
第六章为结论部分，对全文内容进行了总结。
In this paper, seven iV-containing compounds were synthesized and characterized by elemental analysis, IR spectra, ~1H NMR and X-ray crystallographic analysis. N-containing compounds coordinated with transitional metal were synthesized and the electrochemical nature and the interaction with DNA were investigated.
In the first chapter, the classification of heterocyclic compounds, application and research progress, especially benzoic-nitrogenous heterocyclic compounds, thiazole compounds and the research and application of imidazole compounds were introduced.
In the second chapter, with o-diaminobenzene as the original material, five series of compounds, such as amide, benzothiobiazole and benzimidazole derivatives, were synthesized. The compounds were coordinated with metals to form metal complexes. The compounds were characterized by elemental analysis, IR spectra and ~1H NMR. Five single crystals of them were obtained and their structures were determined by X-ray crystallography method.
In the third chapter, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Cu(C_(16)H_(14)N_2O_2)] and salmon sperm DNA. When DNA was added, the peak current of [Cu(C_(16)H_(14)N_2O_2)] was decreased and the peak potential was not changed. In 0.2 mol·L~(-1) B-R buffer solution, the binding ratio between [Cu(C_(16)H_(14)N_2O_2)] and salmon sperm DNA was calculated to be 2:1 and the binding constant was 6.63×10~5 L~2·mol~(-2).
In the fourth chapter, cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Co(bth)_2(H_2O)_4]~+ and salmon sperm DNA. An electrochemical DNA biosensor for the detection of short DNA sequence related to the human immunodeficiency virus (HIV) was developed with [Co(bth)_2(H_2O)_4]~+ as hybridization indicator. With this approach, a sequence of the HIV could be quantified over the range from 3.2×10~(-7) mol·L~(-1) to 2.9×10~(-6) mol·L~(-1), with a detection limit of 1.1×10~(-7) mol·L~(-1). The electrochemical sensor showed good selectivity.
In the fifth chapter, the process of [Cd(C_7H_6N_2)_2]~(2+) on glassy carbon electrode might be a quasi-reversible reaction controlled neither by adsorption nor by diffusion. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used to investigate the interaction between [Cd(C_7H_6N_2)_2]~(2+) and salmon sperm DNA. The results show that the mode of the interaction of DNA with [Cd(C_7H_6N_2)_2]~(2+) is intercalative. The novel hybridization indicator, bis(benzimidazole)cadmium(II) dinitrate (Cd(bzim)_2(NO_3)_2), was utilized to develop an electrochemical DNA biosensor for the detection of short DNA sequence related to the hepatitis B virus (HBV). With this approach, a sequence of the HBV could be quantified over the range from 1.49×10~(-7) mol·L~(-1) to 1.06×10~(-6) mol·L~(-1), with a linear correlation of r = 0.9973 and a detection limit of 8.4×10~(-8) mol·L~(-1). The [Cd(C_7H_6N_2)_2]~(2+) signal observed from probe sequence before and after hybridization with four bases mismatch containing sequence was lower than that observed after hybridization with complementary sequence, showing good selectivity. These results demonstrate that the indicator [Cd(C_7H_6N_2)_2]~(2+) provides great promise for rapid and specific measurement of target DNA.In the last chapter, it was summarized for the whole thesis.
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