Synthesis, Crystal Structure and Property of a Binuclear Copper Complex [Cu2L2(pht)2]2·H2O①

HU Xi-Ln SHI Peng-Fei JIANG Qin XU Rui-Bo YIN Fu-Jun WANG D-Qi

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Synthesis, Crystal Structure and Property of a Binuclear Copper Complex [Cu2L2(pht)2]2·H2O①

HU Xi-Lana, b②SHI Peng-FeiaJIANG QinaXU Rui-BoaYIN Fu-JunaWANG Da-Qic

a(222005)b(222005)c(252059)

A new binuclear copper complex,[Cu2L2(pht)2]2·H2O (Hpht = 5,5-diphenylhy- dantoin, i.e. phenytoin; L = 2-diethylaminoethanol), has been synthesized by the solvothermal method, and characterized by elemental analysis, IRand single-crystal X-ray diffraction. The crystal belongs to the monoclinic system, space group2/with= 31.918(3),= 12.9222(15),= 19.868(2) ?,= 98.762(2)o,= 8098.8(16) ?3,= 1.429 Mg/m3,= 4,(000) = 3640,= 1.107 mm-1,= 0.0560 and= 0.1276 (> 2()). Each copper(II) in a molecule is coordinated with N and O atoms from ligand L and N atom from ligand Hpht in a tetradentate manner. Moreover, two copper(II) centers are bridged by two O atoms of hydroxyl groups from two L ligands to form a slightly distorted binuclear {Cu2O2} diamond configuration. In addition, the interaction of this complex with calf thymus DNA (CT-DNA) was investigated by UV-vis spectrum and viscometry, and the complex may bind to DNA through intercalation.

copper(II) complex, synthesis, crystal structure, DNA binding

1 INTRODUCTION

Copper is the active center of multiple enzymes that play unique roles in the redox system of organism, and studies on the interaction of copper complexes with DNA help to understand the patho- genic mechanism of certain diseases and the thera- peutic mechanism of certain drugs, which means much for developing novel high-efficient and low- toxic drugs, screening new drugs, and upgrading drugs for chemotherapy and anti-cancer drugs[1-5]. Phenytoin is a bio-ligand using its N and O atoms to participate in coordination with various configura- tions, and the complexes formed by phenytion and transition metals have wide biological and pharma- cological activities[6-14]. Therefore, we synthesized a new tetra-nuclear cupper complex by solvothermal method. It was fully characterized and analyzed by infrared spectra, elemental analysis and X-ray single-crystal diffraction analysis. The interaction with calf thymus DNA was also studied using UV- vis spectroscopy and viscosimetry.

2 EXPERIMENTAL

2. 1 Materials and instruments

The elemental analysis was performed by Perkin Elmer 240 elemental analyzer; The crystal data were collected by a Bruker Smart-1000 single-crystal dif- fractometer; Infrared spectrum was determined by WGH-30/6 double-beam infrared spectroscopy (KBr pellet, Tianjin Gangdong SCI & TECH Develop- ment Co., Ltd.); Electron absorption spectrum was recorded by UV-Vis 2550 spectrophotometer (Japan Shimadzu). Calf thymus DNA (CT-DNA, US Sigma), ethidium bromide (EB, Fluka), copper acetate, N,N-diethylethanolamine, phenytion and methanol were all analytically pure reagents.

2. 2 Synthesis of [Cu2L2(pht)2]2H2O

1.0089 g (1 mmol) of phenytoin and 0.7991 g (1 mmol) of Cu(Ac)2·H2O were dissolved in 10 mL of methanol, then 5 mL of 0.4 mol/dm3N,N-diethyl- ethanolamine in methanol (2 mmol) was added. The above solution was sealed in a Teflon-lined reaction pot with the filling rate of 80%. The pot was heated at 393 K for 40 h under self-generated pressure, then gradually cooled down to room temperature at a rate of 10℃/h. The dark green precipitate was collected by filtration and re-dissolved in the mixture of methanol and chloroform (v:v = 1:1). Dark green cube-like crystals suitable for X-ray crystallography analysis were obtained by slow vaporization in several days. IR(KBr): 3442(w), 1640(m), 1421 (s) cm-1. Elemental analysis for Cu4C84H102N12O13, calc.: C, 57.92; H, 5.90; N, 9.65%. Found: C, 57.57; H, 5.78; N, 10.09%.

2. 3 Crystal structure analysis

A single crystal with dimensions of 0.20mm × 0.16mm × 0.14mm was chosen for data collection which was performed on a Bruker Smart-CCDsingle-crystal diffractometer equipped with a gra- phite-monochromatic Mo-radiation (= 0.071073 nm) using an-scan mode at 298(2) K. In the range of 1.70≤≤25.01°, a total of 19838 reflections were collected, of which 7111 (int= 0.0576) were independent, and 3904 were observed with> 2() and used to solve the structure. The final refinement converged at= 0.0560,= 0.1276 (= 1/[2(F2) + (0.0565)2+ 26.1174], where= (F2+ 2F2)/3),= 1.020, (Δ)max= 0.638 and (Δ)min= –0.473 e/?3. Software SHELXL-97 was adopted to analyze and refine the crystal structure. All hydrogen and non-hydrogen atoms were refined by anisotropic thermal parameters, and refined further through full-matrix least-squares method on2. The hydrogen atoms were placed at the calculated positions.

2. 4 Interaction with DNA

2. 4. 1 UV-Vis titration of the complex in the presence of DNA[5]

The electron absorption spectra of DNA and DNA+EB systemswere performed in and without the presence of the copper complex. The con- centration of the Tris-NaCl buffer solution (pH = 7.42) was 50 mmol?L-1. The absorption data were recorded by gradually titrating 10 μL of the complex solution (1.03 mmol?L-1) into the DNA solution (2 mL DNA in tris-NaCl buffer, 2.5 × 10-5mol?L-1) and DNA+EB mixture (200 uL 2.5 × 10-5mol?L-1EB and 2 mL 2.5 × 10-5mol?L-1DNA in tris-NaCl buffer), respectively.

2. 4. 2 DNA viscosity determination[17]

The viscosity was determined at (25 ± 0.1) ℃. The relative viscosity of the sample solution was calculated by formula= (–0)/0, where0andare the time for the buffer and DNA solution (containing the complex of different concentration) to flow through the capillary, respectively.ηis the relative viscosity of DNA solution without complex. The effect of the copper complex on the viscosity of DNA was revealed by the plot (η/η)1/3.(=Complex/DNA).

3 RESULTS AND DISCUSSION

3. 1 Infrared spectrum

The infrared spectrum of the title complex showed a blue shift of 77 cm-1(1640 cm-1) for the amide I band (C=O) in the imidazole ring of ligand phenytion as compared with that in the original ligand (1717 cm-1), indicating that the N atom in imidazole was coordinated with copper(II); additionally, the pre- sence of N,N-diethylethanolamine in the complex was proved by the peaks located at 3442(-OH/-NH) and 1421 cm-1.

3. 2 Crystal structure determination

The crystal structure of this complex is shown in Fig. 1, and the packing diagram of unit cells in Fig. 2.The selected bond lengths and bond angles are listed in Table 1, and the related hydrogen bonds are given in Table 2.

Table 1. Selected Bond Lengths (?) and Bond Angles (°) for the Title Complex

Symmetry codes: #1: –+3/2, –+1/2, –+1; #2: –+1,, –+3/2

Table 2. Hydrogen Bonding Parameters (?, °) for the Title Complex

Fig. 1. Molecular structure of the title complex

Fig. 2. 3D framework of Cu(1) in the title complex

Two trans-2-(N,N-diethylethanolamine)-2-pheny-tion-copper(II) and one crystal water molecule were comprised in the binuclear copper complex. Two copper(II) ions were bridged through a hydroxyl oxygen in N,N-diethylethanolamine to form a binuclear (Cu2O2) diamond configuration. The bond lengths and bond angles in each trans-2-(N,N- diethylethanolamine)-2-phenytion-copper(II) diffe- red from each other (Table 1), which may be attribu- ted to the steric hindrance associated with the ring formed by the coordination of benzene ring of ligand phenytion with N,N-diethylethanolamine. Cu(1)– Cu(1)#1 and Cu(2)–Cu(2)#2 were bridged by the hydroxyl oxygen atom in each N,N-diethylethanol- amine into a binuclear configuration, with the Cu(1)–Cu(1)#1 and Cu(2)–Cu(2)#2 bonds to be 0.30175 and 0.29934 nm, respectively; The sum of angles for O(3)–Cu(1)–O(3)#1, N(2)–Cu(1)–O(3)#1, O(3)–Cu(1)–N(3) and N(2)–Cu(1)–N(3) is 360.2o, and that for O(6)–Cu(2)–O(6)#2, O(6)#2–Cu(2)– N(5), O(6)–Cu(2)–N(6) and N(5)–Cu(2)–N(6) 361.5o. The above analysis demonstrated that each copper(II) in this complex formed a slightly distor- ted diamond configuration in a tetradentate manner and weak metallic bonds were found between two copper atoms[5]. The Cu(1) molecules are connected with each other along theaxisto generate a chainthrough intermolecular hydrogen bonds (Fig. 2). Meanwhile, the Cu(2) molecules are also connected with each other through inter(intra)molecular hydro- gen bonds (Fig. 3). The mean Cu–N bond in the complex (1.974 ?) is longer than that in the pre- viously reported tetra-nuclear copper[6](1.949 ?) and tri-nuclear copper[7](1.961 ?), but shorter than the value in complexes formed by mono-nuclear copper[8, 9], binuclear[10]copper and phenytion. The above differences may be attributed to the steric hindrance of complexes and the coordination mode.

3. 3 Interaction with CT-DNA

3. 3. 1 Absorption spectrum associated with the interaction of the complex with CT-DNA

Fig. 4 shows a strong absorption peak at 260 nm before CT-DNA reacting with the complex, and this is a typical UV absorption peak of DNA bases. The maximal absorption peak changed dramatically after CT-DNA reacting with this complex with the occurrence of a noticeable hyperchromic effec, which may be ascribed to the intercalation of the complex into the bases of DNA. The intercalation leads to the couple of unoccupiedorbitals of ligand with the electron-filledorbital of DNA bases, causing the drop of→*orbital energy and the reduction of transition probability[5, 16, 17].

Fig. 3. 3D framework of Cu(2) in the title complex

Fig.4. UV-vis absorption spectra of DNA changed along with the addition of the complex

3. 3. 2 Effect on the electron absorption spectrum of EB-DNA system

In the presence of CT-DNA and EB, titration of this complex with incremental quantities to the above system would give rise to a hyperchromic effect on the absorption spectrum of EB-DNA system (Fig. 5) with a distinct red shift in the absorption maxima. Based on Long’s theory, hyperchromicity and red-shift are characteristic in the interaction between the coordination complex and DNA bases. The hyperchromicity indicates that the complex is close to the DNA bases, that is, the complex may be intercalated into the DNA bases leading to a strong electronic interaction between them[5].

3. 3. 3 Viscosity analysis of the interaction between this complex and DNA

Viscosimetry is very important to detect thecom- bination of complex with DNA. The viscosity curve reflecting the interaction between complex and DNA (curve 2 in Fig. 6) showed that the relative viscosity of DNA increased along with gradual addition of the complex, which further proved its interaction with DNA through intercalation[18]. This result was in accordance with that of the above UV-Vis absorption analysis. However, as is reflected by the viscosity curve oftetra-nuclear copper[6](curve 3 in Fig. 6) and tri-nuclear copper[7](curve 1 in Fig. 6), the interaction of this complex with DNA was weaker than the tri-copper complex, which may be attributed to the weaker steric hindrance of this complex than the latter.

Fig. 5. Absorption spectra of EB-DNA in the presence of the complex

Fig. 6. Effects of increasing the quantity of the complex on the viscosity of DNA

4 CONCLUSION

A new binuclear copper complex[Cu2L2(pht)2]2· H2O has been solvothermally synthesized. It consists of two copper(II) ions, and each copper(II) is coor- dinated by nitrogen atom from N,N-diethyl- ethanolamine and nitrogen atom from phenytion. Both the two Cu(II) ions are bridged by the hydroxyl group to form a binuclear diamond configuration. This complex may bind to CT-DNA through inter- calation.

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13 September 2013;

24 June 2014 (CCDC 685782)

① This work was supported by the National Natural Science Foundation of China (No. 21101069), Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (13KJB150005), the Open Foundation of Jiangsu Key Laboratory of Marine Biotechnology (No. HS12006) and the Priority Academic Program Development of Jiangsu Higher Education Institutions

. E-mail: huxl@hhit.edu.cn or huxilan836@sohu.com