CN109053814B - 一种荧光探针钌配合物、合成方法及其应用 - Google Patents
一种荧光探针钌配合物、合成方法及其应用 Download PDFInfo
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Abstract
本发明公开了一种荧光探针钌配合物、合成方法及其应用,该配合物以5‑醛基‑1,10‑邻菲咯啉为配体与钌离子配位得到,在邻菲咯啉的5位引入强吸电子的醛基,与金属钌配位得到六配位的钌配合物,用作荧光探针检测半胱氨酸和同型半胱氨酸,该探针对半胱氨酸和同型半胱氨酸表现了高灵敏度、高选择性的识别。其它干扰物质存在下,荧光强度也没有明显变化,表现了强的干扰能力。该探针响应速度快,具有宽的pH应用范围,并且不需要加入有机溶剂,可在100%水相中检测半胱氨酸和同型半胱氨酸的钌配合物荧光探针。
Description
技术领域
本发明属于有机合成技术领域,具体涉及一种荧光探针钌配合物、合成方法及其应用。
背景技术
含巯基的氨基酸如半胱氨酸和高半胱氨酸对维持人体生理平衡起着关键的作用。例如,半胱氨酸和高半胱氨酸对细胞与生物体内组织器官的生长是必不可少的。半胱氨酸的缺乏会造成严重的人体健康问题,如生长缓慢、头发脱色、皮肤损伤、肌肉和脂肪损失以及肝脏损害等。而缺乏高半胱氨酸更加危险,它能导致老年痴呆症、心血管疾病与骨质疏松症等疾病。所以,检测半胱氨酸与高半胱氨酸意义重大。
在现有的检测生物硫醇的技术中,荧光分析法相对于与其它几种方法具有操作简便、选择性好、灵敏度高、响应时间短、实时成像等优点,在生命科学及分析化学领域具有广泛的应用前景。
目前报道的基于醛基类型的荧光探针可避免细胞内大量存在的谷胱甘肽(1mM)对探针识别半胱氨酸和同型半胱氨酸的干扰,但是,报道的多数有机小分子探针具有短发射波长、小斯托克斯位移(Stokes shifts)且具有细胞毒性的缺点,因为长的发射波长能够减少探针检测过程中的背景荧光和活细胞的光损伤,大斯托克斯位移能够提高检测的灵敏度;并且与半胱氨酸反应速度较慢,一般需要1h左右;而且很少能在100%水相中完成检测,通常需要在有机溶剂中进行检测。至今还没有报道过一种具有大斯托克斯位移,在100%水相中检测半胱氨酸和同型半胱氨酸的基于钌配合物的红光荧光探针。
发明内容
本发明的目的是克服现有技术的不足,提供一种荧光探针钌配合物、合成方法及其应用。
本发明提供了一种荧光探针钌配合物,该钌配合物的结构式如下:
优选的,所述钌配合物的阴离子为Cl-。
本发明提供了一种荧光探针钌配合物的合成方法,包括如下步骤:
1)二氯-四(二甲基亚砜)合钌的合成:RuCl3溶于二甲基亚砜中,回流,冷却,加入丙酮,得到的沉淀洗涤,干燥即得;
2)二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌的合成:将二氯-四(二甲基亚砜)合钌与5-醛基-1,10-邻菲咯啉溶于三氯甲烷,回流,除去溶剂,再加溶剂溶解,抽滤,干燥即得;
3)二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌的合成:二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌与5-醛基-1,10-邻菲咯啉溶于有机溶剂中,氩气下回流,冷却,得到的反应液用氯化钠溶液和丙酮的混合溶液梯度洗脱,向洗脱下的溶液中加入六氟磷酸钾,得到的沉淀用二氯甲烷萃取,然后干燥除水,过滤,蒸去溶剂,即得;
4)二氯-三(5-醛基-1,10-邻菲咯啉)合钌的合成:将二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌溶于甲醇中,加入氯型阴离子交换树脂,搅拌,过滤旋干,即得产物。
优选的,步骤1)所述回流温度为80℃。
优选的,步骤2)所述5-醛基-1,10-邻菲咯啉的合成步骤为:将5-甲基-1,10-邻菲咯啉,二氧化硒和1,2-二氯苯混合,在氮气保护下反应,反应完后冷却,过滤得到的滤液酸化,酸化后的溶液经过洗涤中和,然后萃取多次,合并有机相,干燥除水,过滤,蒸去溶剂,得5-醛基-1,10-邻菲咯啉。
优选的,所述5-甲基-1,10-菲咯啉、二氧化硒和1,2-二氯苯三者的摩尔比为1:3:420。
优选的,步骤2)所述二氯-四(二甲基亚砜)合钌与5-醛基-1,10-邻菲咯啉的质量比为1:4.4。
优选的,步骤3)所述二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌与5-醛基-1,10-邻菲咯啉的质量比为1.2:1。
优选的,步骤3)所述梯度洗脱的洗脱液为浓度为1mol/L氯化钠溶液和丙酮的混合液,两者的体积比为10:1。
本发明还提供了一种荧光探针钌配合物的应用,该钌配合物可用作荧光探针识别半胱氨酸和同型半胱氨酸。
本发明的合成路线原理如下:
荧光检测手段因其简便通用及低成本而用于生物巯基小分子检测。相比有机小分子探针,过渡金属配合物具有大的斯托克斯位移(Stokes shifts),可使用可见光激发,长的激发寿命等优良的光物理性质。特别是钌配合物还具有低毒优点。然而,报道的钌配合物检测半胱氨酸和同型半胱氨酸需在有机溶剂或高比例的有机溶剂和水的混和溶剂,如二甲基亚砜:水=9:1。一方面是因为现有钌配合物本身不溶水需有机溶剂溶解,另一方面可能是在100%水相中这些探针的醛基单元与巯基小分子反应程度低。因此,现有的钌配合物用于检测半胱氨酸和同型半胱氨酸,需要加入有机溶剂,但是有机溶剂大多对细胞具有毒性,对生物体造成不利的影响。
邻菲咯啉具有优异的配位能力和良好的稳定性,并且水溶性较好,通过亲核取代或亲电取代在邻菲咯啉的不同位置上引入取代基和官能团,改变邻菲咯啉的配位结构,得到许多新颖的以邻菲咯啉为基体的新型配体。目前用作分子荧光探针配合物的邻菲咯啉衍生物配体,通常是引入供电子的取代基,如王鹏等发表在应用化学学报《疏水型邻菲咯啉铁(Ⅱ)配合物的合成、表征及其电化学行为》中在邻菲咯啉的中引入甲基或者是酰胺基取代基,供电子的取代基(酰胺基的供电效应)能够提高邻菲咯啉中N原子的电子密度,有利于电子能量在原子间的有效传递,促进其与金属之间的配位。若是邻菲咯啉中引入吸电子的取代基,将会降低N原子的电子密度,使得金属离子与邻菲咯啉衍生物配位时,很难从N原子获得电子,使得结合能升高,增加配位的难度,并且最终得到的金属配合物其荧光效应不明显甚至不会表现出荧光特性。因此,本领域的技术人员不会想到将醛基这种强吸电子基团用作邻菲咯啉的取代基。目前也没有出现将醛基作为取代基合成邻菲咯啉衍生物,与金属离子配位得到的配合物用于荧光探针检测半胱氨酸和同型半胱氨酸,而是将醛基取代到其他配体上与邻菲咯啉衍生物共同与金属离子配位得到配合物(如专利申请号CN201110068877.0可溶于水体系的磷光铱配合物及其制备方法),这也从侧面证实了将醛基直接取代到邻菲咯啉上有困难,并且与金属离子之间难以配位。
本发明通过研究发现,在邻菲咯啉的5位引入强吸电子的醛基,与金属钌配位得到六配位的钌配合物,用作荧光探针检测半胱氨酸和同型半胱氨酸,该探针对半胱氨酸和同型半胱氨酸表现了高灵敏度、高选择性的识别。其它干扰物质存在下,荧光强度也没有明显变化,表现了强的干扰能力。该探针响应速度快,具有宽的pH应用范围,并且不需要加入有机溶剂,可在100%水相中检测半胱氨酸和同型半胱氨酸的钌配合物荧光探针。
目前,技术人员为了增加荧光探针金属配合物在水中的溶解性,通常以邻菲咯啉衍生物为配体,但是一方面,由于邻菲咯啉衍生物中含有多个六元环,其空间位阻大,会降低配合物的反应活性,另一方面是其与金属钌配位得到的配合物,通常会导致背景荧光的增加,影响检测的灵敏度,因此将吸电子醛基直接连接在邻菲咯啉上,邻菲咯啉衍生物与金属钌以3:1配位,可有效降低背景荧光,也可减小与检测物反应的空间位阻。同时由于钌配合物的六氟磷酸盐不溶于水,因此在使用过程中需要加入有机溶剂作为反应介质,而将钌配合物的六氟磷酸根转换成氯盐可获得良好的水溶性。因此根据现有的方法较难单独以邻菲咯啉衍生物为配体与钌离子配位得到荧光背景弱、水溶性好及空间位阻小且不影响反应活性的六配位钌配合物,通常是将邻菲咯啉衍生物与其他空间位阻较小的配体共同配合得到六配位的钌配合物,如南开大学陈华梅2007年发表的学位论文《基于邻菲罗啉等芳香体系的受体的合成及其阴离子传感研究》中47页显示如下所示的两种钌和钴的配合物,这也进一步证实了现有技术中难以得到荧光背景弱的以邻菲咯啉衍生物为配体与钌离子配位得到六配位的钌配合物,并且其作为探针分子,水溶性差,需在有机溶剂中反应、探针响应速度慢。
本发明合成钌配合物的方法中,先将5-甲基-1,10-邻菲咯啉(5-CHO-phen)在二氧化硒和1,2-二氯苯的共同作用下合成5-CHO-phen,此方法得到的5-CHO-phen纯度高,并且产率达到了75%;得到5-CHO-phen后并不是直接与RuCl3配位,而是将RuCl3先与二甲基亚砜作用得到二氯-四(二甲基亚砜)合钌,再加入5-醛基-邻菲咯啉反应,此种处理方法能够使5-醛基-邻菲咯啉与钌离子充分反应,形成稳定的钌配合物;得到的二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌再分别加入与5-醛基-1,10-邻菲咯啉反应后,加入和六氟磷酸钾,最后加入氯型阴离子交换树脂,得到目标产物。本发明的合成方法简单,与常规合成方法相比,反应温和,产率高,成本低,实现了单独以邻菲咯啉衍生物为配体与钌离子配位得到六配位的钌配合物,得到的钌配合物氯盐水溶性良好,并且钌配合物可在100%水相中对半胱氨酸和同型半胱氨酸检测,且具有高灵敏度,高选择性,响应速度快,宽的pH应用范围等优点。
将荧光探针化合物溶于4-羟乙基哌嗪乙磺酸缓冲溶液((10mM HEPES buffer,pH=7.0)配制成10μM的溶液,分别加入各种生理氨基酸(Ala,Ser,Trp,Met,Gln,Val,Arg,Phe,Pro,Thr,Gly,Lys,His,Asp,Ile,Asn,Leu,Glu)和GSH,BSA,荧光没有明显变化。而加入Cys和Hcy后荧光明显增强,该探针对半胱氨酸和同型半胱氨酸表现了高灵敏度、高选择性的识别。
本发明的有益效果是:
1、本发明在邻菲咯啉的5位引入强吸电子的醛基,与金属钌配位得到六配位的钌配合物,用作荧光探针检测半胱氨酸和同型半胱氨酸,该探针对半胱氨酸和同型半胱氨酸表现了高灵敏度、高选择性的识别。其它干扰物质存在下,荧光强度也没有明显变化,表现了强的干扰能力。该探针响应速度快,具有宽的pH应用范围,并且不需要加入有机溶剂,可在100%水相中检测半胱氨酸和同型半胱氨酸的钌配合物荧光探针。
2、本发明的合成方法简单,与常规合成方法相比,反应温和,产率高,成本低,易提纯,实现了单独以邻菲咯啉衍生物为配体与钌离子配位得到六配位的钌配合物,并且钌配合物对半胱氨酸和同型半胱氨酸检测具有高灵敏度,高选择性,响应速度快,宽的pH应用范围,可在100%水相中检测。
3、本荧光探针具有大的斯托克斯位移(Stokes shifts),激发峰为450nm,与半胱氨酸和同型半胱氨酸反应后最大发射峰位置为597nm,斯托克斯位移为147nm,并且探针响应速度快,能在10min内达到荧光最大值。
附图说明
图1为本荧光探针钌配合物的核磁共振氢谱。
图2为本荧光探针钌配合物的高分辨质谱图谱。
图3为本荧光探针与半胱氨酸作用的高分辨质谱图谱。
图4为本荧光探针与同型半胱氨酸作用的高分辨质谱图谱。
图5为本荧光探针(10μM)在10mM HEPES缓冲溶液(pH=7.0)中分别与80μM半胱氨酸和同型半胱氨酸作用的荧光光谱图谱。
图6为本荧光探针(10μM)在10mM HEPES缓冲溶液中不同pH下分别与80μM半胱氨酸和同型半胱氨酸作用的荧光光谱图谱。
图7为本荧光探针(10μM)在10mM HEPES缓冲溶液中分别与半胱氨酸和同型半胱氨酸作用的荧光强度随时间变化图,其中0-10min:0μM,10-20min:20μM;20-30min:40μM。
图8为本荧光探针(10μM)在10mM HEPES缓冲溶液中分别与半胱氨酸(Cys)、同型半胱氨酸(Hcy)作用及其它生理氨基酸的荧光强度图,其中Cys和Hcy浓度为60μM,其它生理氨基酸浓度为100μM。
图9为本荧光探针(10μM)在10mM HEPES缓冲溶液中在半胱氨酸、同型半胱氨酸与其它生理氨基酸、BSA和小牛胸腺DNA共存时的荧光响应图,其中Cys和Hcy浓度为60μM,其它生理氨基酸浓度为100μM。
图10为本荧光探针(10μM)在10mM HEPES缓冲溶液中荧光强度随半胱氨酸浓度变化的荧光光谱,插图为荧光强度与半胱氨酸浓度的线性关系。
图11为本荧光探针(10μM)在10mM HEPES缓冲溶液中荧光强度随同型半胱氨酸浓度变化的荧光光谱,插图为荧光强度与同型半胱氨酸浓度的线性关系。
具体实施方式
下面结合实施例对本发明的具体实施方式做进一步描述,并不因此将本发明限制在所述的实施例范围内。
实施例1
5-醛基-1,10-邻菲咯啉的合成(5-CHO-phen):将5-甲基-1,10-邻菲咯啉(0.04g,0.2mmol),二氧化硒(0.07g,0.6mmol)及1,2-二氯苯(99%,9.3mL,12.14g,82mmol)加入到100mL三颈烧瓶中,在氮气保护下反应,反应2h后冷却至室温,过滤得到的滤液用1mol/L的盐酸酸化,酸化后的溶液用二氯甲烷洗涤,再用饱和碳酸氢钠水溶液中和,然后用7mL二氯甲烷萃取三次,合并有机相,无水硫酸镁干燥除水,过滤,蒸去溶剂,得浅灰白色固体5-醛基-1,10-邻菲咯啉;产量:0.3g;收率:75%;
1)二氯.四(二甲基亚砜)合钌(Ru(DMSO)4Cl2)的合成:1g RuCl3溶于5mL二甲基亚砜中,回流30min,冷却,加入丙酮,得到的黄色沉淀分别用丙酮和乙醚洗涤,干燥即得;
2)二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌的合成:将0.5g Ru(DMSO)4Cl2与0.22g5-CHO-phen溶于20mL三氯甲烷,回流1h,除去溶剂,再加丙酮溶解,抽滤,干燥即得;
3)二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌([Ru(5-CHO-phen)3](PF6)2)的合成:二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌0.24g与5-CHO-phen 0.2g溶于10mL乙二醇中,氩气下回流4h,冷却到室温,得到的反应液装入SP Sephadex C-25阳离子交换柱(3×20cm),用1mol/L的氯化钠水溶液和丙酮混合溶液(体积比10:1)梯度洗脱,向洗脱下的溶液中加入六氟磷酸钾,得到的红色沉淀用100mL的二氯化碳萃取,然后用无水硫酸钠干燥除水,过滤,蒸去溶剂,即得红色固体产物[Ru(5-CHO-phen)3](PF6)2,产量:0.436g。收率:85.9%;
4)二氯-三(5-醛基-1,10-邻菲咯啉)合钌的合成[Ru(5-CHO-phen)3]Cl2:20mg的([Ru(5-CHO-phen)3](PF6)2)溶于10mL的甲醇中,加入氯型阴离子交换树脂(AmberliteIRA-402),搅拌过夜,过滤旋干,即得产物。
通过核磁共振(NMR)、基质辅助激光解析时间飞行质谱(MALDI-TOF-MS)等表征实施例1得到的荧光探针钌配合物,MALDI-TOF-MS(CH3CN):m/z=726.251([M-2PF6-H]+),872.384([M+PF6]+)。其核磁共振氢谱为:1H NMR(400MHz,ppm,CD3CN-d3):10.53(S,3H;CHO),9.38(d,J=8.4Hz,3H;phen4),8.92(S,3H;phen6),8.79(d,J=4.0Hz,3H;phen7),7.93(dd,J1=J2=5.2Hz,3H;phen2),7.65(dd,J1=J2=5.2Hz,3H;phen9),7.65(t,J1=J2=8.4Hz,6H;phen3,8)。
本荧光探针钌配合物的高分辨质谱图谱如图1,m/z=932.644对应在水相中探针与半胱氨酸反应的离子峰,m/z=960.649对应于水相中探针与同型半胱氨酸反应的离子峰,说明其探针作用机理如下式:
将本荧光探针分子溶于4-羟乙基哌嗪乙磺酸缓冲溶液((10mM HEPES buffer,pH=7.0)配制成10μM的溶液,分别加入各种生理氨基酸(Ala,Ser,Trp,Met,Gln,Val,Arg,Phe,Pro,Thr,Gly,Lys,His,Asp,Ile,Asn,Leu,Glu)和GSH,BSA,荧光没有明显变化。而加入Cys和Hcy后荧光明显增强,该探针对半胱氨酸和同型半胱氨酸表现了高灵敏度、高选择性的识别。其它干扰物质存在下,荧光强度也没有明显变化,表现了强的干扰能力。该探针响应速度快,具有宽的pH应用范围。
本荧光探针与半胱氨酸和同型半胱氨酸作用的高分辨质谱图谱分别如图3和4,从图中可以看出,半胱氨酸和同型半胱氨酸能够与探针钌配合物发生反应。
本荧光探针(10μM)在10mM HEPES缓冲溶液(pH=7.0)中分别与80μM半胱氨酸和同型半胱氨酸作用,其荧光光谱图谱如图5,从图中可以看出本荧光探针与半胱氨酸和同型半胱氨酸反应后最大发射峰位置为597nm,斯托克斯位移为147nm。
本荧光探针(10μM)在10mM HEPES缓冲溶液中不同pH下分别与80μM半胱氨酸和同型半胱氨酸作用,其荧光光谱图谱如图6,本荧光探针本荧光探针可应用于较宽的pH范围,在pH为5-10的范围内可实现对半胱氨酸和同型半胱氨酸的检测。
本荧光探针(10μM)在10mM HEPES缓冲溶液中分别与半胱氨酸和同型半胱氨酸作用,其荧光强度随时间变化图如图7。从图中可以看出,本荧光探针对半胱氨酸和同型半胱氨酸具有快的响应速度,在加入4倍当量的半胱氨酸和同型半胱氨酸,在几秒内荧光强度约达到最大值的75.9%,且10分钟内达到荧光最大值。
本荧光探针(10μM)在10mM HEPES缓冲溶液中分别与半胱氨酸、同型半胱氨酸及其它生理氨基酸作用,其荧光强度图如图8,其中半胱氨酸、同型半胱氨酸浓度为60μM,其它生理氨基酸的浓度为100μM。从图中可以看出,本荧光探针具有良好的选择性。探针分子的检测体系为4-羟乙基哌嗪乙磺酸缓冲溶液((10mM HEPES buffer,pH=7.0)。在加入7.5倍当量的半胱氨酸(Cys)后,探针在597nm处荧光强度增大了13.6倍,加入7.5倍当量的同型半胱氨酸(Hcy)后,探针在597nm处荧光强度增大了12.8倍。而加入12倍当量其它生理氨基酸(Ala,Ser,Trp,Met,Gln,Val,Arg,Phe,Pro,Thr,Gly,Lys,His,Asp,Ile,Asn,Leu,Glu和GSH,BSA),仅观察到微弱的荧光变化。
本荧光探针(10μM)在10mM HEPES缓冲溶液中在半胱氨酸、同型半胱氨酸与其它生理氨基酸、BSA和小牛胸腺DNA共存时的荧光响应图如图9,其中半胱氨酸、同型半胱氨酸浓度为60μM,其它生理氨基酸的浓度为100μM。从图中可以看出,本荧光探针表现了强的干扰能力,在Cys,Hcy,Ala,Ser,Trp,Met,Gln,Val,Arg,Phe,Pro,Thr,Gly,Lys,His,Asp,Ile,Asn,Leu,Glu,GSH,BSA,CT-DNA共存时,探针荧光强度没有明显变化。
本荧光探针(10μM)在10mM HEPES缓冲溶液中荧光强度随半胱氨酸浓度和同型半胱氨酸浓度变化的荧光光谱分别如图10和11,其中插图分别为荧光强度与半胱氨酸浓度和同型半胱氨酸浓度的线性关系。从图中可知本荧光探针灵敏度高,随着半胱氨酸和同型半胱氨酸浓度的增加,荧光强度逐渐增加。半胱氨酸和同型半胱氨酸浓度与探针荧光强度在0μM-35μM范围内成线性关系,半胱氨酸检测限为0.83μM,同型半胱氨酸检测限为0.67μM。
对比例1
1)二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌([Ru(5-CHO-phen)3](PF6)2)的合成:100mL三颈烧瓶,将5-醛基-1,10-邻菲咯啉(0.0832g,0.4mmol),RuCl3(0.0207g,0.1mmol)溶于20mL乙醇中,氮气保护下油浴下加热回流6小时。冷到室温,将反应液装入SPSephadex C-25阳离子交换柱(3×20cm),用1mol/L氯化钠水溶液:丙酮(体积比10:1)混合溶液梯度洗脱,向洗脱下的溶液中加入六氟磷酸钾,得到的红色沉淀用100mL的二氯化碳萃取,然后用无水硫酸钠干燥除水,过滤,蒸去溶剂,即得红色固体[Ru(5-CHO-phen)3](PF6)2,产量:0.0622g,收率:61.3%;
2)二氯-三(5-醛基-1,10-邻菲咯啉)合钌的合成[Ru(5-CHO-phen)3]Cl2:20mg的([Ru(5-CHO-phen)3](PF6)2)溶于10mL的甲醇中,加入氯型阴离子交换树脂(AmberliteIRA-402),搅拌过夜,过滤旋干,即得。
从上述数据可知,将得到5-CHO-phen直接与RuCl3配位,相比于本发明将RuCl3先与二甲基亚砜作用得到二氯-四(二甲基亚砜)合钌,再加入5-醛基-邻菲咯啉反应,其合成方法得到的产物收率低。
Claims (9)
2.如权利要求1所述荧光探针钌配合物的合成方法,其特征在于,包括如下步骤:
1)二氯-四(二甲基亚砜)合钌的合成:RuCl3溶于二甲基亚砜中,回流,冷却,加入丙酮,得到的沉淀洗涤,干燥即得;
2)二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌的合成:将二氯-四(二甲基亚砜)合钌与5-醛基-1,10-邻菲咯啉溶于三氯甲烷,回流,除去溶剂,再加溶剂溶解,抽滤,干燥即得;
3)二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌的合成:二氯-二(二甲基亚砜)-5-醛基-邻菲咯啉合钌与5-醛基-1,10-邻菲咯啉溶于乙二醇中,氩气下回流,冷却,得到的反应液用氯化钠溶液和丙酮的混合溶液梯度洗脱,向洗脱下的溶液中加入六氟磷酸钾,得到的沉淀用二氯甲烷萃取,然后干燥除水,过滤,蒸去溶剂,即得;
4)二氯-三(5-醛基-1,10-邻菲咯啉)合钌的合成:将二(六氟磷酸根)三(5-醛基-1,10-邻菲咯啉)合钌溶于甲醇中,加入氯型阴离子交换树脂,搅拌,过滤旋干,即得产物。
3.如权利要求2所述荧光探针钌配合物的合成方法,其特征在于,步骤1)所述回流温度为80℃。
4.如权利要求2所述荧光探针钌配合物的合成方法,其特征在于,步骤2)所述5-醛基-1,10-邻菲咯啉的合成步骤为:将5-甲基-1,10-邻菲咯啉,二氧化硒和1,2-二氯苯混合,在氮气保护下反应,反应完后冷却,过滤得到的滤液酸化,酸化后的溶液经过洗涤中和,然后萃取多次,合并有机相,干燥除水,过滤,蒸去溶剂,得5-醛基-1,10-邻菲咯啉。
5.如权利要求4所述荧光探针钌配合物的合成方法,其特征在于,所述5-甲基-1,10-菲咯啉、二氧化硒和1,2-二氯苯三者的摩尔比为1:3:420。
6.如权利要求2所述荧光探针钌配合物的合成方法,其特征在于,步骤2)所述二氯-四(二甲基亚砜)合钌与5-醛基-1,10-邻菲咯啉的质量比为1:4.4。
7.如权利要求2所述荧光探针钌配合物的合成方法,其特征在于,步骤3)所述二氯.二(二甲基亚砜)-5-醛基-邻菲咯啉合钌与5-醛基-1,10-邻菲咯啉的质量比为1.2:1。
8.如权利要求2所述荧光探针钌配合物的合成方法,其特征在于,步骤3)所述氯化钠溶液的浓度为1mol/L。
9.如权利要求1所述荧光探针钌配合物的应用,其特征在于,该钌配合物可用作荧光探针识别半胱氨酸和同型半胱氨酸。
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