基于一种酰腙和咪唑配体的铜(Ⅱ)、镍(Ⅱ)配合物的水热合成、晶体结构及体外抗癌活性

引用本文: 高平章, 陈雅心, 郑敏敏, 王景梅, 解庆范, 陈延民. 基于一种酰腙和咪唑配体的铜(Ⅱ)、镍(Ⅱ)配合物的水热合成、晶体结构及体外抗癌活性[J]. 无机化学学报, 2016, 32(9): 1572-1578. doi: 10.11862/CJIC.2016.198 shu

Citation: GAO Ping-Zhang, CHEN Ya-Xin, ZHENG Min-Min, WANG Jing-Mei, XIE Qing-Fan, CHEN Yan-Min. Syntheses, Crystal Structures and in Vitro Antitumor Activities of Copper(Ⅱ) and Nickel(Ⅱ) Complexes Based on Acylhydrazone and Imidazole Ligands[J]. Chinese Journal of Inorganic Chemistry, 2016, 32(9): 1572-1578. doi: 10.11862/CJIC.2016.198 shu

基于一种酰腙和咪唑配体的铜(Ⅱ)、镍(Ⅱ)配合物的水热合成、晶体结构及体外抗癌活性

泉州师范学院化工与材料学院，泉州 362000

通讯作者: 陈延民, E-mail：qzucym@163.com; 会员登记号：S06N5449M1311(解庆范)，S06N2113M1304(陈延民)

基金项目:
泉州师范学院学科建设资金和福建省大学生创新创业训练计划项目 201510399025

泉州师范学院学科建设资金和福建省大学生创新创业训练计划项目 201510399030

摘要: 采用水热法合成了5-硝基水杨醛缩噻吩-2-甲酰腙的铜和镍配合物[Cu(Him)L]₂ (1)和[Ni(Him)L] (2)(H₂L=5-硝基水杨醛缩噻吩-2-甲酰腙，Him=咪唑)并经元素分析、红外光谱和紫外光谱表征。X射线单晶衍射分析表明，1的晶体属单斜晶系，空间群P2₁/c，晶胞参数：a=1.135 68(12) nm，b=0.770 45(8) nm，c=2.140 4(2) nm，β=97.405(3)°。2的晶体属三斜晶系，空间群P1，晶胞参数：a=0.726 91(4) nm，b=0.976 34(6) nm，c=1.265 74(8) nm，α=79.533(2)°，β=82.862(2)°，γ=68.985(2)°。1是中心对称的双核配合物，Cu(Ⅱ)处于四方锥配位环境；2是单核配合物，Ni(Ⅱ)处于平面四边形的配位环境。化合物1通过N-H…O氢键形成一维超分子链，而化合物2通过N-H…O和C-H…O氢键形成二维超分子网络。初步研究了配体和配合物的体外抗癌活性。结果表明，配合物1和2对人肝癌细胞HEPG2和人结肠癌细胞SW620均有较强的增殖抑制作用。

关键词:

酰腙
/ 配合物
/ 晶体结构
/ 抗癌活性

English

Syntheses, Crystal Structures and in Vitro Antitumor Activities of Copper(Ⅱ) and Nickel(Ⅱ) Complexes Based on Acylhydrazone and Imidazole Ligands

College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou, Fujian 362000, China

Corresponding author: CHEN Yan-Min, qzucym@163.com

Received Date: 02 May 2016
Revised Date: 17 June 2016
Available Online: 10 September 2016

Abstract: Two new complexes [Cu(Him)L]₂ (1) and [Ni(Him)L] (2), where H₂L is 2-thiophenecarboxylic acid (2-hydroxly-5-nitro-benzylidene)-hydrazide and Him is imidazole, were synthesized by hydrothermal reaction and characterized by elemental analysis, FT-IR and electronic spectra. The structure of complexes has been accomplished by single crystal X-ray diffraction which results confirmed that the crystal of 1 belongs to the monoclinic system, space group P2₁/c with cell parameters: a=1.135 68(12) nm, b=0.770 45(8) nm, c=2.140 4(2) nm, β=97.405(3)° and the crystal of 2 belongs to the triclinic system, space group P1 with cell parameters: a=0.726 91(4) nm, b=0.976 34(6) nm, c=1.265 74(8) nm, α=79.533(2)°, β=82.862(2)°, γ=68.985(2)°. The X-ray analyses revealed that 1 displays a centrosymmetric binuclear structure with the Cu atoms in square pyramidal coordination. The binuclear units are further linked by hydrogen bonds to generate an infinite 1D chain. The mononuclear units in 2 are linked through weak N-H…O and C-H…O hydrogen bonds to form an infinite 2D network. The in vitro antitumor activities of ligand and complexes were tested by MTT method, which results show that 1 and 2 have strong in vitro antitumor activity against HEPG2 and SW620 cancer cells lines. CCDC: 1041671, 1; CCDC 1041672, 2.

Key words:

自从1969年美国化学家Rosenberg等^[1]发现顺铂对肿瘤有强烈抑制作用后，金属配合物作为抗癌药物成为非常活跃的研究领域^[2]，非铂系金属配合物的抗癌活性更是受到极大的关注。铜和镍都是生物必需的微量元素，在生物过程中扮演着重要角色^[3-4]。例如，铜参与电子传递、氧化还原等许多生命过程，人体内至少有11种氧化酶含有铜；而镍可以促进铁的吸收和氨基酶的合成，同时镍在DNA和RNA的结构中还起到稳定剂的作用。许多研究表明，铜配合物^[5-9]和镍配合物^[10-12]具有抗菌、抗病毒、抗炎、抗肿瘤等作用。另外，酰腙类Schiff碱配位环境与生物系统相似，其配合物具有良好的抗肿瘤、抗氧化、抗菌等多种生物活性^[13-18]，因而备受关注。早在20世纪70年代就已发现此类Schiff碱的抗肿瘤活性的构效关系^[19]：① 水杨醛比其他醛制得的Schiff碱的抗肿瘤活性好；② 取代基拉电子能力越强抗仲瘤效果越好。因此，本文以5-硝基水杨醛与噻吩-2-甲酰肼反应合成了一种新的酰腙型Schiff碱(Scheme 1)，并用水热法合成了咪唑为第二配体的铜和镍配合物，分析了它们的晶体结构和体外抗癌活性。

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下载: 全尺寸图片幻灯片

图 1 配合物1的晶体结构(椭球率30%)

Figure 1 Crystal structure of complex 1 with 30% probability ellipsoid

Symmetry code: ^ⅰ1-x, 2-y, -z

下载: 全尺寸图片幻灯片

图 2 化合物1中的分子间氢键和π…π相互作用

Figure 2 Intermolecular hydrogen bonds and π…π interactions in 1

Cg1: O3-C4-C3-C7-N2; Cg2: C1-C2-C3-C4-C5-C6; Symmetry codes: ^ⅱ1+x, 1+y, z; ^ⅲ1-x, 1-y, 2-z

下载: 全尺寸图片幻灯片

图 3 配合物2的晶体结构(椭球率30%)

Figure 3 Crystal structure of complex 2 with 30% probability ellipsoid

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图 4 配合物2中分子间的C-H…O和N-H…O氢键

Figure 4 Intermolecular C-H…O and N-H…O hydrogen bonds in 2

Symmetry code: ^ⅰ2-x, -y, -z; ^ⅱ-1+x, y, 1+z

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图 5 配体H₂L及其配合物的紫外可见光谱

Figure 5 UV-Vis spectra of ligand H₂L and complexes 1 and 2

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图 6 配体H₂L和配合物对HEPG2的抑制作用

Figure 6 Inhibition effects of ligand H₂L and the complexes on cell HEPG2

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图 7 配体H₂L和配合物对SW620的抑制作用

Figure 7 Inhibition effects of ligand H₂L and the complexes on cell SW620

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表 1 化合物的晶体数据

Table 1. Crystal data of the compounds

	1	2
Empirical formula	C₃₀H₂₂Cu₂N₁₀O₈S₂	C₁₅H₁₁N₅NiO₄S
Formula weight	841.78	416.06
Crystal system	Monoclinic	Triclinic
Space group	P2₁/c	P1
a/nm	1.135 68(12)	0.726 91(4)
b/nm	0.770 45(8)	0.976 34(6)
c/nm	2.140 4(2)	1.265 74(8)
α/(°)	90	79.533(2)
β/(°)	97.405(3)	82.862(2)
γ/(°)	90	68.985(2)
V/nm³	1.857 2(3)	0.822 90(9)
Z	2	2
D_c/(g·cm^-3)	1.505	1.679
Absorption coefficient/mm^-1	1.318	1.339
F(000)	852	424
Reflections collected, unique	4 261, 2 930 (R_int=0.017)	2 939, 2 939 (R_int=0.000)
Data, restraints, parameters	4 261, 0, 254	2 939, 3, 236
Goodness-of-fit on F²	1.05	1.07
Final R indices [I > 2σ(I)]	R₁=0.037 8, wR₂=0.086 5	R₁=0.057 7, wR₂=0.137 9
R indices (all data)	R₁=0.048 3, wR₂=0.089 2	R₁=0.075 6, wR₂=0.144 7
Largest diff. peak and hole/(e·nm^-3)	470 and -350	991 and -645

下载: 导出CSV

表 2 配合物1和2的主要键长和键角

Table 2. Selected bond lengths (nm) and angles (°) of 1 and 2

1
Cu1-N2	0.190 94(18)	Cu1-O3	0.190 03(15)	Cu1-O4	0.192 45(17)
Cu1-N4	0.193 70(19)	Cu1-O3^ⅰ	0.277 87(16)	O1-N1	0.120 0(3)
O2-N1	0.124 4(3)	C4-O3	0.128 9(3)	C8-O4	0.128 3(3)
N1-C1	0.144 7(3)	C7-N2	0.128 6(3)	N2-N3	0.139 5(3)
C8-N3	0.129 7(3)	N4-C15	0.133 8(3)	N4-C13	0.136 6(3)
N5-C15	0.130 6(4)	N5-C14	0.138 4(4)	Cu1…Cu1^ⅰ	0.345 5(2)
N2-Cul-O3	93.20(7)	O4-Cu1-N2	81.44(7)	O3-Cu1-O4	173.74(7)
N2-Cul-N4	169.52(8)	O3-Cu1-N4	93.27(8)	O4-Cu1-N4	92.51(8)
O3-Cu1-O3^ⅰ	86.70(6)	N2-Cu1-O3^ⅰ	98.16(6)	O3^ⅰ-Cu1-O4	90.86(4)
O3^ⅰ-Cu1-N4	90.44(7)
2
Ni1-N2	1.827(4)	Ni1-O2	1.827(3)	Ni1-01	1.841(3)
Ni1-N4	1.903(4)	N2-C6	1.295(6)	N1-C5	1.307(6)
N1-N2	1.393(6)	O1-C5	1.296(6)	O2-C12	1.299(6)
N2-Ni1-O2	95.55(17)	N2-Ni1-O1	83.99(17)	O2-Ni1-O1	177.08(16)
N2-Ni1-N4	173.22(18)	O2-Ni1-N4	89.43(16)	O1-Ni1-N4	91.27(17)
Symmetry codes: ^ⅰ1-x, 2-y, -z for 1

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表 3 配合物1的氢键参数

Table 3. Hydrogen bond parameters for complex 1

D-H…A	d(D-H)/nm	d(H…A)/nm	d(D…A)/nm	∠DHA/(°)
N5-H5A…O2^ⅱ	0.086	0.202 0	0.286 5(3)	166.0
Symmetry codes: ^ⅱ1+x, 1+y, z

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表 4 2的氢键参数

Table 4. Hydrogen bond parameters for 2

D-H…A	d(D-H)/nm	d(H…A)/nm	d(D…A)/nm	∠DHA/(°)
C1-H1…O3^ⅰ	0.093	0.254	0.338 7(8)	151
N5-H5A…O3^ⅱ	0.086	0.214	0.298 17(7)	166
Symmetry codes: ^ⅰ2-x, -y, -z; ^ⅱ-1+x, y, 1+z

下载: 导出CSV

表 5 配体H₂L和配合物对癌细胞的半数抑制浓度IC₅₀

Table 5. IC₅₀ values of ligand H₂L and the complexes on cancer cell

μg·mL-¹
Compound	HEPG2	SW620
1	1.30	2.22
2	2.77	2.97
H₂L	11.28	17.86

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基于一种酰腙和咪唑配体的铜(Ⅱ)、镍(Ⅱ)配合物的水热合成、晶体结构及体外抗癌活性

通讯作者: 陈延民, E-mail：qzucym@163.com; 会员登记号：S06N5449M1311(解庆范)，S06N2113M1304(陈延民)

English

Syntheses, Crystal Structures and in Vitro Antitumor Activities of Copper(Ⅱ) and Nickel(Ⅱ) Complexes Based on Acylhydrazone and Imidazole Ligands

Corresponding author: CHEN Yan-Min, qzucym@163.com

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

基于一种酰腙和咪唑配体的铜(Ⅱ)、镍(Ⅱ)配合物的水热合成、晶体结构及体外抗癌活性

通讯作者: 陈延民, E-mail：qzucym@163.com; 会员登记号：S06N5449M1311(解庆范)，S06N2113M1304(陈延民)

English

Syntheses, Crystal Structures and in Vitro Antitumor Activities of Copper(Ⅱ) and Nickel(Ⅱ) Complexes Based on Acylhydrazone and Imidazole Ligands

Corresponding author: CHEN Yan-Min, qzucym@163.com

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

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