N-(2-吡啶甲基)-L-丝氨酸铜配合物的合成、晶体结构及抑制蛋白酪氨酸磷酸酶活性

doi:10.7503/cjcu20160563

高等学校化学学报 ›› 2016, Vol. 37 ›› Issue (12): 2138.doi: 10.7503/cjcu20160563

• 研究论文: 无机化学 • 上一篇下一篇

N-(2-吡啶甲基)-L-丝氨酸铜配合物的合成、晶体结构及抑制蛋白酪氨酸磷酸酶活性

李艳红^1,², 袁彩霞¹, 卢丽萍¹(), 朱苗力¹, 付学奇³, 邢述³(), 高增强⁴

1. 山西大学分子科学研究所, 化学生物学与分子工程教育部重点实验室, 太原 030006
2. 山西医科大学汾阳学院, 汾阳 032200
3. 吉林大学生命科学学院, Edmond H. Fischer细胞信号传导实验室, 长春 130012
4. 中国科学院高能物理研究所北京同步辐射中心, 北京 100049

收稿日期:2016-08-08 出版日期:2016-12-10 发布日期:2016-11-21
作者简介:联系人简介: 卢丽萍, 女, 博士, 教授, 博士生导师, 主要从事生物无机化学研究. E-mail:luliping@sxu.edu.cn ; 邢述, 男, 博士, 副教授,主要从事蛋白质酪氨酸激酶(PTKs)及蛋白质酪氨酸磷酸酶(PTPs)的结构与功能的研究. E-mail:xingshu@jlu.edu.cn
基金资助:
国家自然科学基金(批准号: 21471092, 21571118, 21271121)资助

Synthesis,Crystal Structure and Protein Tyrosine Phosphatase Inhibition of a Copper(Ⅱ) Complex with N-(2-Pyridylmethyl)-L-serine^†

LI Yanhong^1,², YUAN Caixia¹, LU Liping^1,^*(), ZHU Miaoli¹, FU Xueqi³, XING Shu^3,^*(), GAO Zengqiang⁴

1. Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan 030006, China
2. Fenyang College Shanxi Medical University, Fenyang 032200, China
3. Edmond H. Fischer Signal Transduction Laboratory, College of Life Science, Jilin University, Changchun 130012, China
4. Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences,Beijing 100049, China

Received:2016-08-08 Online:2016-12-10 Published:2016-11-21
Contact: LU Liping,XING Shu E-mail:luliping@sxu.edu.cn;xingshu@jlu.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21471092, 21571118, 21271121)

摘要/Abstract

摘要：

在甲醇溶液中, 还原希夫碱HL[N-(2-吡啶甲基)-L-丝氨酸]与CuCl₂·2H₂O以摩尔比1∶1反应, 得到1个新的中性单核铜配合物[CuLCl(H₂O)](Ⅰ). 通过X射线单晶衍射、元素分析、红外光谱、电喷雾质谱和粉末X射线衍射分析等对其进行了表征. 晶体结构分析表明, 在该配合物中还原希夫碱以三齿双螯合环配位到中心铜离子, 同时氯离子和溶剂水分子也参与配位, 形成1个具有四方锥构型的五配位铜(Ⅱ)配合物, 该配合物通过分子间弱相互作用连接成二维超分子结构. 生物活性测试结果表明, 配合物Ⅰ能有效抑制蛋白酪氨酸磷酸酶1B(PTP1B)和T细胞蛋白酪氨酸磷酸酶(TCPTP), IC₅₀值分别为0.32和0.45 μmol/L.

关键词: 铜(Ⅱ)配合物, N-(2-吡啶甲基)-L-丝氨酸, 抑制剂, 蛋白酪氨酸磷酸酶1B(PTP1B), T细胞蛋白酪氨酸磷酸酶(TCPTP)

Abstract:

The reaction of the reduced Schiff base HL [N-(2-pyridylmethyl)-L-serine] with CuCl₂·2H₂O in molar ratio of 1∶1 in methanol solution afforded a new neutral mononuclear complex [CuLCl(H₂O)](Ⅰ). The structure was determined by single-crystal X-ray diffraction and further characterized by elemental analysis, FTIR, electrospray ionization mass spectrometry and powder X-ray diffraction. In complex Ⅰ, the Cu(Ⅱ) ion adopts five-coordinated mode in a square pyramidal configuration which is completed by one oxygen and two nitrogen atoms from the L^- anion, one chloride anion and one water molecule. The discrete copper coordination units were extended into a 2D supramolecular network through the intermolecular interactions. The bioactivity of the compound as a potential PTPs(Protein Tyrosine Phosphatases) inhibitory agent in vitro was investigated, displaying potent inhibition against PTP1B(IC₅₀=0.32 μmol/L) and TCPTP(IC₅₀=0.45 μmol/L).

Key words: Copper(Ⅱ) complex, N-(2-Pyridylmethyl)-L-serine, Inhibitor, PTP1B, TCPTP

中图分类号:

O614.121

TrendMD:

李艳红, 袁彩霞, 卢丽萍, 朱苗力, 付学奇, 邢述, 高增强. N-(2-吡啶甲基)-L-丝氨酸铜配合物的合成、晶体结构及抑制蛋白酪氨酸磷酸酶活性. 高等学校化学学报, 2016, 37(12): 2138.

LI Yanhong, YUAN Caixia, LU Liping, ZHU Miaoli, FU Xueqi, XING Shu, GAO Zengqiang. Synthesis,Crystal Structure and Protein Tyrosine Phosphatase Inhibition of a Copper(Ⅱ) Complex with N-(2-Pyridylmethyl)-L-serine^†. Chem. J. Chinese Universities, 2016, 37(12): 2138.

图/表 8

参考文献 35

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CCDC number	1494101	Z	2
Empirical formula	C₉H₁₃ClCuN₂O₄	D_c/(g·cm^-3)	1.811
Formula weight	312.20	μ/mm^-1	2.218
Radiation type	Synchrotron(beamline 3W1A at BSRF), λ=0.07200 nm	F(000) θ range for data collection/(°)	318 3.309—25.999
T/K	100	Limiting indices	-7≤h≤0; -7≤k≤7;
Crystal system	Monoclinic		-17≤l≤17
Space group	P2₁	Reflections collected, unique	1974, 1886(R_int=0.0318)
a/nm	0.6377(1)	Completeness to θ(%)	98.6(θ=25.595°)
b/nm	0.6375(1)	Data/restraints/parameters	1886/1/155
c/nm	1.4400(3)	GOF on F²	1.137
α/(°)	90	Final R indices[I>2σ(I)]	R₁=0.0414, wR₂=0.1163
β/(°)	102.07(3)	R indices(all data)	R₁=0.0411, wR₂=0.1161
γ/(°)	90	(Δρ)_max,(Δρ)_min /(e·nm^-3)	729 and -860
V/nm³	0.5725(2)

CCDC number	1494101	Z	2
Empirical formula	C₉H₁₃ClCuN₂O₄	D_c/(g·cm^-3)	1.811
Formula weight	312.20	μ/mm^-1	2.218
Radiation type	Synchrotron(beamline 3W1A at BSRF), λ=0.07200 nm	F(000) θ range for data collection/(°)	318 3.309—25.999
T/K	100	Limiting indices	-7≤h≤0; -7≤k≤7;
Crystal system	Monoclinic		-17≤l≤17
Space group	P2₁	Reflections collected, unique	1974, 1886(R_int=0.0318)
a/nm	0.6377(1)	Completeness to θ(%)	98.6(θ=25.595°)
b/nm	0.6375(1)	Data/restraints/parameters	1886/1/155
c/nm	1.4400(3)	GOF on F²	1.137
α/(°)	90	Final R indices[I>2σ(I)]	R₁=0.0414, wR₂=0.1163
β/(°)	102.07(3)	R indices(all data)	R₁=0.0411, wR₂=0.1161
γ/(°)	90	(Δρ)_max,(Δρ)_min /(e·nm^-3)	729 and -860
V/nm³	0.5725(2)

Cu1—O1	0.1970(5)	Cu1—N2	0.1997(5)	Cu1—O4	0.2362(5)
Cu1—Cl1	0.22417(17)	Cu1—N1	0.2009(5)
O1—Cu1—N1	82.7(3)	N2—Cu1—Cl1	98.43(18)	N1—Cu1—O4	90.6(2)
O1—Cu1—Cl1	95.04(15)	O1—Cu1—N2	166.3(2)	N1—Cu1—N2	83.7(3)
O1—Cu1—O4	90.6(2)	N1—Cu1—Cl1	165.1(2)	N2—Cu1—O4	88.4(2)
Cl1—Cu1—O4	104.21(13)

Cu1—O1	0.1970(5)	Cu1—N2	0.1997(5)	Cu1—O4	0.2362(5)
Cu1—Cl1	0.22417(17)	Cu1—N1	0.2009(5)
O1—Cu1—N1	82.7(3)	N2—Cu1—Cl1	98.43(18)	N1—Cu1—O4	90.6(2)
O1—Cu1—Cl1	95.04(15)	O1—Cu1—N2	166.3(2)	N1—Cu1—N2	83.7(3)
O1—Cu1—O4	90.6(2)	N1—Cu1—Cl1	165.1(2)	N2—Cu1—O4	88.4(2)
Cl1—Cu1—O4	104.21(13)

D—H…A	d(D—H)/nm	d(H…A)/nm	d(D…A)/nm	ÐDHA/(°)
O3—H3…O1^a	0.0840	0.1975	0.2810	172.79
O4—H4C…O2^b	0.0820	0.2323	0.2919	130.03
O4—H4D…O2^c	0.0820	0.1963	0.2774	169.98
N1—H1…Cl1^a	0.1000	0.2582	0.3401	139.04
C4—H4B…O4^a	0.0990	0.2469	0.3392	154.84
C9—H9…Cl1	0.0950	0.2792	0.3355	118.91

N-(2-吡啶甲基)-L-丝氨酸铜配合物的合成、晶体结构及抑制蛋白酪氨酸磷酸酶活性

Synthesis,Crystal Structure and Protein Tyrosine Phosphatase Inhibition of a Copper(Ⅱ) Complex with N-(2-Pyridylmethyl)-L-serine^†

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