CN111848652B - 一种金属铜配合物及其制备方法和应用 - Google Patents
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Abstract
本发明涉及一种金属铜配合物,其化学式为:[Cu(Bpybc)1.5(H2O)3].SO4;其中Bpybc配体为1,1’‑二(4‑苯甲酸基)‑4,4’‑联吡啶,将配体二氯化1,1’‑二(4‑苯甲酸)‑4,4’‑联吡啶溶于蒸馏水,用盐酸调节pH至1~3,再滴加CuSO4·5H2O的水溶液;在20~40℃下充分反应,过滤,滤液室温放置缓慢挥发,析出蓝色块状晶体后,过滤收集产品。该金属铜配合物可作为蛋白酪氨酸磷酸酶1B抑制剂。
Description
技术领域
本发明涉及金属铜配合物,特别是一种在胰岛素信号传导中起关键作用的蛋白酪氨酸磷酸酶1B (protein tyrosine phosphatases 1B,PTP1B)抑制剂金属铜配合物。
背景技术
蛋白质酪氨酸磷酸化是细胞代谢、信号传导及细胞周期调控的重要调节步骤,其中通过对许多生物体内的信号传导途径起着正向或负向的调节作用,其作用异常能引发许多人类疾病,包括:癌症,糖尿病,类风湿病及高血压等。PTP1B基因敲除小鼠实验研究表明,在肌肉和肝脏的胰岛素信号传导中PTP1B起重要的负向调节作用,缺失PTP1B小鼠的胰岛素敏感性明显增加,并对肥胖有一定的抵抗作用,通过抑制PTP1B可增加胰岛素和瘦蛋白的活性,这为寻找治疗II型糖尿病、肥胖等相关疾病的新型药物提供了光明前景。
目前已知的有机分子PTP1B抑制剂主要包括一些生物底物模拟物、变构抑制剂和作用位点尚不明确的其他抑制剂,其中大多数高效、高选择性的小分子抑制剂,由于化合物本身容易电离、细胞渗透性和生物利用度不是很理想,因而难以成为有治疗价值的药物。无机化合物在有机体中的吸收利用率低,且有一定的毒性,常见的有:肠胃不舒服、恶心、呕吐和腹泻等,这些毒副作用限制了其在药物领域的广泛应用。2002年,英国哥伦比亚大学的J.H. McNeill等人发现了一种以麦芽酚配位的氧钒配合物(BMOV),见下图,
其包含有机配体,比简单的无机盐脂溶性好、细胞渗透能力强,因而生物利用度高,达到同样疗效所需剂量小,大大降低了毒性,更适合成为一类理想的糖尿病治疗剂,至此寻找合适的有机金属配合物成为现在糖尿病潜在药物研究和开发的热点之一
发明内容
本发明要解决的技术问题是提供一种在室温生理条件下可以作为糖尿病靶蛋白PTP1B抑制剂的金属铜配合物,及该金属铜配合物的制备方法。
为解决以上技术问题,根据本发明的一个方面,提供一种金属铜配合物,其化学式为:[Cu(Bpybc)1.5(H2O)3].SO4;其中Bpybc配体为1,1’-二(4-苯甲酸基)-4,4’-联吡啶。
上述金属铜配合物,其晶体属于三斜晶系,空间群为
R-3,晶胞参数为:
a =17.8232(14) Å,
b = 17.8232(14) Å,
c = 26.987(2) Å ,
α =
β= 90.00°,
γ= 120°;该金属铜配合物的对称结构单元是由一个Cu2+、三个Bpybc配体分子、三个配位水分子、一个硫酸根离子组成,其中,Cu2+周围为CuO6 六配位,与Cu2+配位的六个氧原子分别来自三个配体的三个羧基氧及三个水分子中的氧原子, Cu-O键的键长分别为2.022(8)和2.014(14) Å;该金属铜配合物为一维结构,沿a轴方向形成螺旋链。
根据本发明的另一方面,提供了所述金属铜配合物的制备方法,将配体二氯化1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于蒸馏水,用盐酸调节pH至1~3,再滴加CuSO4·5H2O的水溶液;在室温条件下充分反应,过滤,滤液室温放置缓慢挥发,析出蓝色块状晶体后,过滤收集产品。
进一步地,用浓度为1mol/L的HCl调节pH至1~3。
进一步地,配体与CuSO4·5H2O的摩尔比为1:(1~5)。
进一步地,反应温度20 ~40 ℃ ,反应时间为16~24 h。
根据本发明的另一方面,提供了所述金属铜配合物作为蛋白酪氨酸磷酸酶1B抑制剂的应用。
本发明是基于1,1’-二(4-苯甲酸基)-4,4’-联吡啶和铜(II)构筑的室温条件下具有抗糖活性的金属铜配合物,该配合物含羧基水溶性好,室温生理条件下具有PTP1B体外抑制活性。
此外,上述金属铜配合物的制备方法工艺简单,晶体样品纯度高,生长快,收率高。
附图说明
图 1: [Cu(Bpybc)1.5(H2O)3].SO4结构单元图。(为了图片清晰,省略了溶剂分子)
图 2: 本发明配合物的完整配位结构图。(为了图片清晰,省略了氢原子)
图 3:本发明铜配合物抑制PTP1B活性的IC50值测定曲线。
实施方式
金属铜配合物的制备方法
作为本发明一种典型的实施方式,制备上述金属铜配合物时,将配体二氯化1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于蒸馏水,用盐酸调节pH至1~3,再滴加CuSO4·5H2O的水溶液;在室温条件下充分反应,过滤,滤液室温放置缓慢挥发,析出蓝色块状晶体后,过滤收集获得所述金属铜配合物。
在以上实施方式中,优选地,用浓度为1mol/L的HCl调节pH至1~3。配体与CuSO4·5H2O的摩尔比为1:(1~5)。相对具体地,反应温度为20 ~40 ℃ ,反应时间为16~24 h。
该制备方法工艺简单,晶体样品纯度高,生长快,收率高。反应酸性环境及反应物的比例都非常关键。配体Bpybc与CuSO4·5H2O的摩尔比为1: 5得到的晶体质量最好,产率最高。
实施例1.
将0.5 mmol 二氯1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于20mLH2O中,用1mol/LHCl调节pH为3,再将2.5 mmol CuSO4·5H2O加入其中,即配体与金属盐之间的摩尔比为1:5,25 °C搅拌24小时,过滤,得蓝色滤液,25 °C静置挥发,2周后长出蓝色晶体,过滤收集,产率为37 %。
实施例2.
将1.0 mmol二氯1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于20mL H2O中,用1mol/LHCl调节pH至1,再将2.0 mmol CuSO4·5H2O 加入其中,即配体与金属盐之间的摩尔比为1:2,25 °C搅拌24小时,过滤,得蓝色滤液,25 °C静置挥发,3周后长出蓝色晶体,过滤收集,产率为18 %。
实施例3.
将0.5 mmol 二氯1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于20mL H2O中,用1mol/LHCl调节pH至3,再将0.5 mmol CuSO4·5H2O加入其中,即配体与金属盐之间的摩尔比为1:1,25 °C搅拌20小时,过滤,得蓝色滤液,25 °C静置挥发,四周后长出少量蓝色晶体,过滤收集,产率为10 %。
实施例4
将0.5 mmol 二氯1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于20mL H2O中,用1mol/LHCl调节pH至3,再将1.5 mmol CuSO4·5H2O加入其中,即配体与金属盐之间的摩尔比为1:3,20 °C搅拌16小时,过滤,得蓝色滤液,20 °C静置挥发,四周后长出少量蓝色晶体,过滤收集,产率为10 %。
实施例5
将0.5 mmol 二氯1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于20mL H2O中,用1mol/LHCl调节pH至2,再将2.0mmol CuSO4·5H2O加入其中,即配体与金属盐之间的摩尔比为1: 4,40 °C搅拌20小时,过滤,得蓝色滤液,40 °C静置挥发,四周后长出少量蓝色晶体,过滤收集,产率为10 %。
配合物的结构
以上实施例获得的金属铜配合物的化学式为:[Cu(Bpybc)1.5(H2O)3].SO4;其中Bpybc配体为1,1’-二(4-苯甲酸基)-4,4’-联吡啶。
以实施例1获得的晶体样品为例,将晶体样品固定在Bruker SMART 1000 CCD面探衍射仪上,以石墨单色器MoKα为辐射光源,收集样品对波长为0.7103Å的X-Ray衍射数据。以ω扫描方式,衍射数据经LP因子和经验吸收校正。全部X-Ray衍射图还原为衍射指标后,用SHELXTL-NT 5.10版程序包,直接法确定X-Ray衍射强度的位相,初始结构经全矩阵最小二乘法做数轮修正,找出全部非氢原子坐标,确认残余峰不再有非氢原子后,做各向异性温度因子处理。C原子采用理论加氢,水分子中O原子上的氢由差值 Fourier 合成给出,(0.93Å ≤ C-H ≤ 0.97Å,0.0843 ≤ O-H ≤ 0.859Å),并固定在母原子上。详细的晶体测定数据见表1。结构单元见图1,完整配位环境见图2。
表1 配合物的晶体学数据
配合物的PTP1B抑制活性测试:
将实施例1获得的金属铜配合物设计浓度梯度从1.0×10-4 ~ 1.0×10-12 mol/L作为抑制组分于酶活性测定体系中(96 孔板), 温浴10 min, PTP1B酶浓度为80 nmol/L, 加入p-NPP (100 mmol/L, 2 µL)启动酶反应, 30 min 后加入NaOH (2 mol/L, 5µL)终止反应, 测定OD405(平行实验三次), 以酶的相对剩余活力对抑制剂浓度的对数作图, 实验中分别采取非酶校正, 溶剂校正。 实验测得配合物半数抑制浓度IC50值约为0.1 μΜ,说明配合物具有较好的抑制PTP1B活性,见图3。
Claims (7)
1.一种金属铜配合物,其特征在于:化学式为:[Cu(Bpybc)1.5(H2O)3].SO4;其中Bpybc配体为1,1’-二(4-苯甲酸基)-4,4’-联吡啶。
2. 根据权利要求1所述的金属铜配合物,其特征在于:其晶体属于三斜晶系,空间群为R-3,晶胞参数为:a = 17.8232(14) Å,b = 17.8232(14) Å,c = 26.987(2) Å ,α =β=90.00°,γ= 120°;该金属铜配合物的对称结构单元是由一个Cu2+、三个Bpybc配体分子、三个配位水分子、一个硫酸根离子组成,其中,Cu2+周围为CuO6 六配位,与Cu2+配位的六个氧原子分别来自三个配体的三个羧基氧及三个水分子中的氧原子, Cu-O键的键长分别为2.022(8)和2.014(14) Å;该金属铜配合物为一维结构,沿a轴方向形成螺旋链。
3.如权利要求1或2所述的金属铜配合物的制备方法,其特征在于:将配体二氯化1,1’-二(4-苯甲酸)-4,4’-联吡啶溶于蒸馏水,用盐酸调节pH至1~3,再滴加CuSO4·5H2O的水溶液;在室温条件下充分反应,过滤,滤液室温放置缓慢挥发,析出蓝色块状晶体后,过滤收集产品。
4.如权利要求3所述的金属铜配合物的制备方法,其特征在于:用浓度为1mol/L的HCl调节pH至1~3。
5.如权利要求3所述的金属铜配合物的制备方法,其特征在于:配体与CuSO4·5H2O的摩尔比为1:(1~5)。
6. 如权利要求5所述的金属铜配合物的制备方法,其特征在于:反应温度为20 ~40 ℃,反应时间为16~24 h。
7.权利要求1或2所述的金属铜配合物在制备抑制蛋白酪氨酸磷酸酶1B药物中的应用。
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Non-Patent Citations (2)
Title |
---|
"联吡啶羧酸铜配合物的合成及其抑制PTP1B 活性研究";李丽等;《试剂与应用》;20201231;第43卷(第3期);第365-369页 * |
"蛋白酪氨酸磷酸酶1B及其抑制剂的研究进展";袁仲等;《中国药科大学学报》;20180225;第49卷(第1期);第1-9页 * |
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