CN108299427A - 咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针及其应用 - Google Patents
咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针及其应用 Download PDFInfo
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Abstract
本发明公开了一种咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针,所述探针是(3‑丁基‑1‑氯‑7‑咪唑并[1,5‑a]吡啶基)(4‑((7‑氯‑2,1,3‑苯并噁二唑)磺酰基)‑1‑哌嗪基)甲酮,其化学结构式如式(1)所示。本发明的荧光探针在DMSO/水(体积比3:7)溶液中对半胱氨酸有较好的荧光选择性、较高的灵敏度及较强的抗其它离子干扰能力,应用前景广泛。
Description
技术领域
本发明涉及有机小分子荧光探针领域,尤其涉及一种新型半胱氨酸荧光探针(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(4-((7-氯-2,1,3-苯并噁二唑) 磺酰基)-1-哌嗪基)甲酮及其应用。
背景技术
半胱氨酸是一种具有生理功能的氨基酸,是组成蛋白质的多种氨基酸中唯一具有还原性基团疏基的氨基酸。研究表明,半胱氨酸与很多疾病有关,比如肾功能衰竭、老年痴呆症等,它们在生物体内的含量变化可以作为这些疾病诊断的依据,因此,半胱氨酸的选择性和灵敏性检测对人类健康具有重要意义。
荧光探针因选择性好,灵敏度高,操作简单,成本低并且可以实现实时监测等优点,现广泛应用于离子的测定。尽管已有多种半胱氨酸荧光探针被报道,但是目前多数探针为单一信号的增强或减弱型探针,具有两个或多个信号响应变化的比率型探针甚少。
发明内容
针对现有技术的不足,本发明解决的问题是提供一种两个信号响应变化的半胱氨酸比率荧光探针(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(4-((7-氯-2,1,3-苯并噁二唑)磺酰基)-1-哌嗪基)甲酮及其应用。
本发明的技术方案是:一种咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针,其化学结构式如式(1)所示:
本发明还包括咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针的应用,式(1)化合物在DMSO/水 (体积比3:7)溶液中对半胱氨酸有较好的荧光选择性。
本发明还包括咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针的合成方法,将(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(1-哌嗪基)甲酮 与4-氯-7-氯磺酰-2,1,3-苯并噁二唑按照摩尔比1:1的投料比例,在TEA催化条件下,常温下反应2-5小时,得到(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(4-((7-氯-2,1,3-苯并噁二唑) 磺酰基)-1-哌嗪基)甲酮。
配制咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针的二甲亚砜溶液,分别加入定量的Cys、Ala、Arg、Asn、Asp、Glu、Gly、His、Leu、Ile、Lys、Met、Phe、Pro、Ser、Val、GSH、Hcy、ACO-、Br-、Ca2+、Cl-、Fe2+、K+、Zn2+、NO2 - 的水溶液,通过荧光光谱测试来研究对不同氨基酸以及阴阳离子的选择性,测其荧光发射波谱强度变化发现: 本发明所述咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针即式(1)化合物对半胱氨酸有较好的荧光选择性,如图1所示。逐渐加入半胱氨酸至60当量后,化合物1在468nm处荧光强度减弱,同时,在563nm处荧光强度明显增强,如图2所示。因此,咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针具有巨大的应用前景。
附图说明
图1:式(1)化合物(5×10-6M)的DMSO/水 (体积比3:7)溶液中,加入60当量的不同氨基酸后的荧光强度变化图。
图2:式(1)化合物(5×10-6M)的DMSO/水 (体积比3:7)溶液中进行半胱氨酸荧光滴定图。图中FL Intensity为光强,Wavelength为波长,equiv为倍数。
图3:式(1)化合物(5×10-6M)和60当量的半胱氨酸共存的DMSO/水 (体积比3:7)溶液中,加入60当量的其它氨基酸后荧光强度比率的变化柱状图。
图4是式(1)化合物合成方法反应式图。
具体实施方式
实施例1:式(1)化合物的合成方案如下式所示:
具体合成步骤如下:
在50 mL圆底烧瓶中依次加入20 mL无水二氯甲烷,0.321g(1.0 mmol)(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(1-哌嗪基)甲酮,0.253g(1.0 mmol)4-氯-7-氯磺酰-2,1,3-苯并噁二唑,0.202g(2.0 mmol)三乙胺(TEA),常温下反应2-5小时,TLC检测反应完成后,加入100 mL二氯甲烷,30 mL水洗三次,二氯甲烷层硫酸钠干燥,浓缩,柱层析得0.321g固体,产率59.7%。
核磁共振氢谱、碳谱测定: 1H NMR (DMSO-d6, 400 MHz), δ 7.98 (d, J = 4.0Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 4.0 Hz, 1H), 7.43 (s, 1H),6.56 (d, J = 4.0 Hz, 1H), 3.77 (s, 4H), 3.42 (s, 4H), 2.93 (t, J = 8.0 Hz,2H), 1.81 (m, 2H), 1.42 (m, 2H), 0.95 (t, J = 8.0 Hz, 3H). 13C NMR (DMSO-d6,100 MHz), δ 168.5, 148.9, 145.4,138.8, 134.7, 129.2, 128.5, 125.9, 123.7,121.2, 120.9, 117.9, 112.1, 46.0, 29.7, 29.0, 26.3, 22.5, 13.8.
实施例2:
向式(1)化合物(5×10-6M)的DMSO/水 (体积比3:7)溶液中加入60当量的Cys、Ala、Arg、Asn、Asp、Glu、Gly、His、Leu、Ile、Lys、Met、Phe、Pro、Ser、Tyr、Val、GSH、Hcy后,测其在468nm以及563nm荧光发射强度比值变化发现:式(1)化合物对半胱氨酸有较好的荧光选择性,其在468nm处荧光强度减弱,同时,在563nm处荧光强度明显增强,I468/I563 = 1.8。
实施例3:
向式(1)化合物(5×10-6M)和60当量的半胱氨酸的DMSO/水 (体积比3:7)溶液中分别加入60当量的Cys、Ala、Arg、Asn、Asp、Glu、Gly、His、Leu、Ile、Lys、Met、Phe、Pro、Ser、Tyr、Val、GSH、Hcy后,测其在468nm以及563nm荧光发射强度比值变化发现:式(1)化合物对其它氨基酸有较强的抗干扰能力,如图3所示。
Claims (2)
1.一种咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针,其特征在于:它是(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(4-((7-氯-2,1,3-苯并噁二唑) 磺酰基)-1-哌嗪基)甲酮,其化学结构式如式(1)所示:
化合物(1)在DMSO/水 (体积比3:7)溶液中对半胱氨酸有较好的荧光选择性。
2.权利要求1所述咪唑并吡啶苯并噁二唑类半胱氨酸比率荧光探针的合成方法,其特征在于:在二氯甲烷溶液中,将(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(1-哌嗪基)甲酮与4-氯-7-氯磺酰-2,1,3-苯并噁二唑按照摩尔比1:1的投料比例,在TEA催化条件下,常温下反应2-5小时,得到(3-丁基-1-氯-7-咪唑并[1,5-a]吡啶基)(4-((7-氯-2,1,3-苯并噁二唑) 磺酰基)-1-哌嗪基)甲酮。
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