氨基苯基苯并咪唑的反应与新荧光化合物的合成
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摘要
2-(2-羟基苯基)苯并咪唑和它的衍生物是一类重要的荧光化合物,具有较大的斯托克斯位移、摩尔消光系数和较高的量子收率。但是由于氨基和苯环相连,大大降低了它和羧基的反应活性。为开发新型的荧光探针,我们将2-(2-羟基-5-氨基苯基)苯并咪唑异硫氰酸酯化,并进一步衍生化合成具有新功能的荧光探针。双光子荧光探针往往具有更大的共轭结构,具有较大的激发长,甚至可以达到近红外激发,从而降低短波激发光对生物组织的伤害和背景生物光对成像的干扰,这是双光子荧光探针成为研究热点的原因。
在生物体内,NO具有非常重要的生物学意义。实现在生物体内对其直接检测有助于促进NO在医药学领域的应用研究。荧光法检测一氧化氮与其它的方法相比具有灵敏度高、即时性好和简单易行等优点,并且荧光法检测和显微镜联用能够实现对细胞内外NO的高分辨成像,可以提供NO在时间和空间上的直观的信息,这是其它检测方法没有的优势。本论文设计合成了新的NO荧光探针,并对其性质进行了研究。
肿瘤的传统诊断和治疗方法毒副作用高,在检测和杀死肿瘤细胞的同时对正常细胞造成严重损伤,影响组织或器官功能恢复。因此研究和开发具有良好选择性、高效性、特异性、无毒或低毒副作用的新型肿瘤诊断方法是现在研究的热门和目标。本论文通过对2-(2-羟基-5-氨基苯基)苯并咪唑修饰,分别合成了生物素和叶酸为靶向结构单元的肿瘤靶向分子荧光探针。
主要研究内容如下:
1.对2-(2-羟基-5-氨基苯基)苯并咪唑的合成方法进行改进。
2.以2-(2-羟基-5-氨基苯基)苯并咪唑为原料通过二硫化碳/重金属盐法合成了2-(2-羟基苯基)苯并咪唑异硫氰酸酯,收率达78.7%;进一步合成了3种新型荧光化合物,并研究了它们与过渡金属钴离子、锰离子、铁离子、铜离子和锌离子配合前后的荧光性质。
3.合成了一种具有双苯并咪唑结构的双光子荧光探针,并研究了它的Cu(II)配合物作为NO荧光探针的性质。
4.合成了生物素作为肿瘤靶向结构单元的新型功能荧光探针和叶酸作为肿瘤靶向结构单元的分子荧光探针,通过红外、核磁等手段对其结构进行了表征,并对其荧光性质进行了研究。
2-(1H-benzo[d]imidazol-2-yl)phenol and its derivatives are important kinds of fluorescent compounds with a wide Stokes shift, a large molar extinction coefficient and a high quantum yield. The ability of 2-(2-Hydroxyphenyl) benzimidazole linking with carboxyl group was reduced due to the conjugation of amine group with aromatic ring. For exploiting new series of fluorescent probe, 2-(2-hydroxyphen-2-yl)benzazole isothiocyanate was synthesized. Furthermore, fluorescent probes with new functions were synthesized.
Two-photon fluorescent probes are of larger conjugate structure compounds with such property as long wave photon as excitation source, even NIR (near infrared) photons as excitation source. Therefore as a kind of detecting technique it can reduce the damage to the tissue and avoid the interferer of tissue auto-fluorescence. It was the reason that this sort fluorescent probe became the research hotspot.
Nitric oxide plays a very important role in physiology of organism. The immediate determination of NO in vivo is helpful for its research in pharmaceutical field. Fluorescent techniques detecting for NO are more sensitive, rapid and simple than traditional methods. The method of fluorescence determination combined with fluorescence microscope can make high-resolution imaging inside and outside the cells come true and can provide the obvious information of NO in time and space, which is the advantage that others have none. In this paper new fluorescent probes detecting for NO were synthesized and its characters were investigated. Conventional methods of detecting or curing tumors make a great side-effect. Common cells are damaged while detecting and killing cancer cells. Thus developing new methods of good selectivity, high efficiency, specificity and none-toxic became the research hotspot. In this study fluorescent probes for targeted detecting tumor mediated folate receptor or biotion receptor were synthesized.
This article includes four parts as follows:
1. Improved method for synthesis of 2 - (2– hydroxyl -5 - amino-phenyl) benzimidazole.
2. 2-(2-hydroxyphen-2-yl )benzazole isothiocyanate was synthesized and a new route concluding disulphide and heavy metallic was created yield 78.7%. Further more there kinds of new fluorescent probes were synthesized and their fluorescent characters for coordinating with transition metallic such as cobalt ions, manganese ions, iron ions, copper ions and zinc ions were studied on.
3. A two-photon fluorescent probe was synthesized. Its coordination compound of Cu(II) being used as a kind of fluorescent probe was determined.
4. Fluorescent probes for targeted detecting tumor mediated folate receptor or biotion receptor were synthesized. The structure of the probes were characterized by 1H NMR, 13C NMR and IR, and the fluorescent properties of the products were determined.
在生物体内,NO具有非常重要的生物学意义。实现在生物体内对其直接检测有助于促进NO在医药学领域的应用研究。荧光法检测一氧化氮与其它的方法相比具有灵敏度高、即时性好和简单易行等优点,并且荧光法检测和显微镜联用能够实现对细胞内外NO的高分辨成像,可以提供NO在时间和空间上的直观的信息,这是其它检测方法没有的优势。本论文设计合成了新的NO荧光探针,并对其性质进行了研究。
肿瘤的传统诊断和治疗方法毒副作用高,在检测和杀死肿瘤细胞的同时对正常细胞造成严重损伤,影响组织或器官功能恢复。因此研究和开发具有良好选择性、高效性、特异性、无毒或低毒副作用的新型肿瘤诊断方法是现在研究的热门和目标。本论文通过对2-(2-羟基-5-氨基苯基)苯并咪唑修饰,分别合成了生物素和叶酸为靶向结构单元的肿瘤靶向分子荧光探针。
主要研究内容如下:
1.对2-(2-羟基-5-氨基苯基)苯并咪唑的合成方法进行改进。
2.以2-(2-羟基-5-氨基苯基)苯并咪唑为原料通过二硫化碳/重金属盐法合成了2-(2-羟基苯基)苯并咪唑异硫氰酸酯,收率达78.7%;进一步合成了3种新型荧光化合物,并研究了它们与过渡金属钴离子、锰离子、铁离子、铜离子和锌离子配合前后的荧光性质。
3.合成了一种具有双苯并咪唑结构的双光子荧光探针,并研究了它的Cu(II)配合物作为NO荧光探针的性质。
4.合成了生物素作为肿瘤靶向结构单元的新型功能荧光探针和叶酸作为肿瘤靶向结构单元的分子荧光探针,通过红外、核磁等手段对其结构进行了表征,并对其荧光性质进行了研究。
2-(1H-benzo[d]imidazol-2-yl)phenol and its derivatives are important kinds of fluorescent compounds with a wide Stokes shift, a large molar extinction coefficient and a high quantum yield. The ability of 2-(2-Hydroxyphenyl) benzimidazole linking with carboxyl group was reduced due to the conjugation of amine group with aromatic ring. For exploiting new series of fluorescent probe, 2-(2-hydroxyphen-2-yl)benzazole isothiocyanate was synthesized. Furthermore, fluorescent probes with new functions were synthesized.
Two-photon fluorescent probes are of larger conjugate structure compounds with such property as long wave photon as excitation source, even NIR (near infrared) photons as excitation source. Therefore as a kind of detecting technique it can reduce the damage to the tissue and avoid the interferer of tissue auto-fluorescence. It was the reason that this sort fluorescent probe became the research hotspot.
Nitric oxide plays a very important role in physiology of organism. The immediate determination of NO in vivo is helpful for its research in pharmaceutical field. Fluorescent techniques detecting for NO are more sensitive, rapid and simple than traditional methods. The method of fluorescence determination combined with fluorescence microscope can make high-resolution imaging inside and outside the cells come true and can provide the obvious information of NO in time and space, which is the advantage that others have none. In this paper new fluorescent probes detecting for NO were synthesized and its characters were investigated. Conventional methods of detecting or curing tumors make a great side-effect. Common cells are damaged while detecting and killing cancer cells. Thus developing new methods of good selectivity, high efficiency, specificity and none-toxic became the research hotspot. In this study fluorescent probes for targeted detecting tumor mediated folate receptor or biotion receptor were synthesized.
This article includes four parts as follows:
1. Improved method for synthesis of 2 - (2– hydroxyl -5 - amino-phenyl) benzimidazole.
2. 2-(2-hydroxyphen-2-yl )benzazole isothiocyanate was synthesized and a new route concluding disulphide and heavy metallic was created yield 78.7%. Further more there kinds of new fluorescent probes were synthesized and their fluorescent characters for coordinating with transition metallic such as cobalt ions, manganese ions, iron ions, copper ions and zinc ions were studied on.
3. A two-photon fluorescent probe was synthesized. Its coordination compound of Cu(II) being used as a kind of fluorescent probe was determined.
4. Fluorescent probes for targeted detecting tumor mediated folate receptor or biotion receptor were synthesized. The structure of the probes were characterized by 1H NMR, 13C NMR and IR, and the fluorescent properties of the products were determined.
引文
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