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Five novel dinuclear copper(II) complexes: Crystal structures, properties, Hirshfeld surface analysis and vitro antitumor activity study
Inorganica Chimica Acta 453 (2016) 507–515
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Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica
Research paper
Five novel dinuclear copper(II) complexes: Crystal structures, properties, Hirshfeld surface analysis and vitro antitumor activity study Hai-Yang Zhang, Wei Wang, Hao Chen, Shu-Hua Zhang ⇑, Yan Li ⇑ College of Chemistry and Bioengineering (Guangxi Key Laboratory of Electrochemical and Magneto-chemical Functional Materials), Guilin University of Technology, Guilin 541004, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 18 April 2016 Received in revised form 26 August 2016 Accepted 8 September 2016 Available online 13 September 2016 Keywords: N,O ligand Dinuclear copper Crystal structure Antitumor activity Self-quenching effect
a b s t r a c t Five dinuclear copper(II) complexes have been synthesized with three kinds of Schiff bases and Cu (NO3)2H2O in different solvent systems: [Cu2(bdhc)(CH3OH)(NO3)(dmf)2] (1), [Cu2(bdhc)(CH3CH2OH) (NO3)(dmf)2] (2) [Cu2(bchc)(CH3CH2OH)(NO3)(dmf)2] (3), [Cu2(bchc)(CH3OH)(NO3)(dmf)2] (4), [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) (H3bdhc is 1,5-bis(3,5-dibromosalicylidene)-carbohydrazide, H3bchc is 1,5-bis(3,5-dichlorosalicylidene)-carbohydrazide, H3bbhc is 1,5-bis(5-bromosalicylidene)-carbohydrazide). All the compounds were characterized by IR spectroscopy, Element analysis and X-ray single-crystal diffraction. The anti-proliferative activity of 1–5 was evaluated against a panel of human tumor cells while 3 exhibited a high antitumor activity against T-24, A549, SK-OV-3 and MGC-803. A detailed analysis of Hirshfeld surface and 2D fingerprint plot revealed that 1–5 were supported mainly by H H, C-H X (X = Cl, Br) and O H intermolecular interactions. Fluorescence properties indicate that all the complexes exist fluorescence concentration self-quenching effect. The magnetic properties of 1 from 2 to 300 K are also discussed. Ó 2016 Elsevier B.V. All rights reserved.
1. Introduction To date, various molecules bearing functional groups have been used in organic and inorganic crystal engineering for designing and synthesis of novel compounds with expectation properties [1–3]. It has been reported that most Schiff bases and its derivative ligands possess versatile bonding modes and they can easily coordinate with metal ions. Moreover, many Schiff base complexes possess fascinating structures and functional applications in medical [4–8], optical [9,10], electrochemical [11,12], magnetic [13–19], luminescence [20–23] and catalytic materials [24–26]. Great efforts have been devoted to the synthesis of novel Schiff bases and its derivative ligands coordinated with metal ions. The exploration of molecular crystal structures through the aspect of intermolecular interactions have aroused much attention recent years [27,28]. As a powerful tool for describing molecular crystal structures, Hirshfeld surfaces analysis is the main approach to identifying the common features of crystals [29–31]. Cancer chemotherapy with platinum drugs has been used since the discovery of cisplatin’s anti-proliferate properties by Rosenberg et al. [32]. Because there are lots of side effects of the platinum⇑ Corresponding authors. E-mail address: [email protected] (S.-H. Zhang). http://dx.doi.org/10.1016/j.ica.2016.09.013 0020-1693/Ó 2016 Elsevier B.V. All rights reserved.
based anticancer drugs, great efforts have been devoted to the synthesis of non-platinum metal-based drugs in order to decrease the side effects [33–35]. The biological chemistry of copper complexes has undergone tremendous research and development in recent years with the increasing number of copper complexes with medicinal applications [36–42]. Many Schiff bases have been utilized in medical materials due to their excellent biological properties. So the medical research of copper(II) complexes derived from Schiff base ligands has been proved as a attractive field [43–46]. In this context, five copper (II) complexes were synthesized by reacting Cu(NO3)2 and three Schiff base ligands (H2bdhc, H2bchc and H2bbhc) in the test tube. Using the MTT method, the anti-proliferative activity of complexes 1–5 was evaluated against a panel of human tumor cells including BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SK-OV-3 and normal human liver HL-7702 cells. 2. Experimental section 2.1. Materials and physical measurements All chemicals were commercially available and used as received without purification. Elemental analyses (CHN) were performed using an PE 2400 series II elemental analyzer. FT–IR spectra were
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recorded from KBr pellets in the ranges 4000–400 cm1 on a BioRad FTS-7 spectrophotometer. The crystal structures were determined on a Agilent G8910A CCD diffractometer using the SHELXS-97 and SHELXL-97 for structure solution and refinement, correspondingly. UV–vis spectra were recorded in the range 200– 800 nm on a UV-2450 spectrophotometer. Luminescence spectra were performed on a Hitachi F-4600 fluorescence spectrophotometer at room temperature. Magnetic measurements were carried out with a Quantum Design PPMS model 600 magnetometer to 5 T for 1. 2.2. Syntheses 2.2.1. [Cu2(bdhc)(CH3OH)(NO3)(dmf)2] (1) A mixture of H3bdhc (0.5 mmol, 0.313 g), DMF (3 mL), CH2Cl2 (2 mL) was transferred to a 15 150 mm test tube. Methanol solution (5 mL) of Cu(NO3)2H2O(0.5 mmol, 0.121 g) was slowly poured into the test tube and then sealed it. Dark green crystals of 1 were collected by filtration after 8 days, and washed with methanol (10 mL 3), then dried in air (yield: 0.133 g, ca. 54.5% based on Cu(NO3)2H2O). Elemental Analysis (%) For 1: C22H25Br4Cu2N7O9 (Mr = 977.19 g/mol), Calc.: C, 27.04; H, 2.59; N, 10.03. Found: C, 26.98; H, 2.54; N, 10.09. IR data for 1 (KBr, cm1) 3429 m, 2928 w, 2366 m, 1642 s, 1604 s, 1496 m, 1434 m, 1388 s, 1219 w, 1157 m, 865 w. 2.2.2. [Cu2(bdhc)(CH3CH2OH)(NO3)(dmf)2] (2) Complex 2 was prepared in a similar way to 1, except that the methanol was replaced by ethanol. Dark Green crystals of 2 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.127 g, ca. 51.2% based on Cu(NO3)2H2O). Elemental Analysis (%) For 2: C23H27Br4 Cu2N7O9 (Mr = 992.24 g/mol), Calc.: C, 27.84; H, 2.74; N, 9.88. Found: C, 27.80; H, 2.79; N, 9.92. IR data for 2 (KBr, cm1) 3413 m, 3121 m, 2335 w, 1650 s, 1612 s, 1496 s, 1434 m, 1381 s, 1211 w, 1157 m, 856 w. 2.2.3. [Cu2(bchc)(CH3CH2OH)(NO3)(dmf)2] (3) Complex 3 was prepared in a similar way to 2, except that the H3bdhc was replaced by H3bchc. Dark Green crystals of 3 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.131 g, ca. 52.7% based on Cu(NO3)2H2O). Elemental Analysis (%) for 3: C23H27Cl4Cu2N7O9 (Mr. = 814.42 g/mol), Calc.: C, 33.92; H, 3.34; N, 12.03. Found: C, 33.90; H, 3.38; N, 12.08. IR data for 3 (KBr, cm1) 3425 w, 3217 w, 2932 w, 1644 s, 1605 s, 1497 s, 1428 s, 1389 s, 1212 w, 1173 m, 872 w. 2.2.4. [Cu2(bchc)(CH3OH) (NO3)(dmf)2] (4) Complex 4 was prepared in a similar way to 3, except that the ethanol was replaced by methanol. Dark Green crystals of 4 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.098 g, ca. 49.4% based on Cu(NO3)2H2O). Elemental Analysis (%) for 4: C22H25Cl4Cu2N7O9 (Mr. = 800.37 g/mol), Calc.: C, 33.05; H, 3.15; N, 12.25. Found: C, 32.99; H, 3.14; N, 12.28. IR data for 4 (KBr, cm1) 3413 m, 3128 m, 2343 w, 1650 s, 1596 s, 1496 s, 1427 s, 1381 s, 1295 w, 1181 m, 865 w. 2.2.5. [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) Complex 5 was prepared in a similar way to 1, except that the H3bdhc was replaced by H3bbhc. Dark Green crystals of 5 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.098 g, ca. 48.3% based on Cu(NO3)2H2O). Elemental Analysis (%) for 5: C21H26Br2Cu2N7O10 (Mr. = 823.39 g/mol), Calc.: C, 30.60; H, 3.30; N, 11.89. Found: C, 30.58; H, 3.26; N, 11.92. IR data for 5 (KBr, cm1) 3409 m, 3231 w, 2930 w, 1639 s, 1609 s, 1501 s, 1423 m, 1377 s, 1176 w, 1122 m, 821 w.
2.3. Crystal structure determination The diffraction data were collected on an Agilent G8910A CCD diffractometer with graphite monochromated Mo-Ka radiation (k = 0.71073 Å), using the x-h scan mode in the ranges 3.01° 6 h 6 25.00° (1), 3.44° 6 h 6 25.01° (2), 2.87° 6 h 6 25.10° (3), 2.90° 6 h 6 25.10° (4), 3.18° 6 h 6 25.00° (5). Raw frame data were integrated with the SAINT program. The structures were solved by direct methods using SHELXS-97 and refined by full matrix least-squares on F2 using SHELXS-97 [47]. An empirical absorption correction was applied with the program SADABS [47]. All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were positioned geometrically and refined as riding. Calculations and graphics were performed with SHELXTL [47]. The anisotropic displacement parameters of the atoms C22, C23 were restrained to be identical with a standard uncertainty of 0.01 Å2 in 1. The highest peak with 1.714 eÅ3 of 1 and 1.282 eÅ3 of 2 in the residual electron density is located 0.74 Å from atom H22a, 0.83 Å from atom H22a, respectively. The detailed crystallographic data and structure refinement parameters are summarized in Table 1. Selected bond lengths and angles for complexes 1–5 are given in Table 2.
2.4. Hirshfeld surface calculations of 1–5 Molecular Hirshfeld surface calculations were performed by using the CrystalExplorer program[48]. When the CIF file of 1 are read into the CrystalExplorer program, all bond lengths to hydrogen were automatically modified to typical standard neutron values (C-H = 1.083 Å, N-H = 1.009 Å and O-H = 0.983 Å) [49]. In this study, all the Hirshfeld surfaces were generated using a high(standard) surface resolution. The 3D dnorm surfaces were mapped by using a fixed color scale of 0.76 (red) to 2.4 (blue). The 2D fingerprint plots were displayed by using the standard 0.4–2.6 Å view with the de and di distance scales displayed on the graph axes.
3. Results and discussion 3.1. structural description 3.1.1. Complexes 1–4 The structures of 1–4 are strikingly similar except the terminal ligands and the halogen substituents of the Schiff base ligands are different (Fig. 1). Therefore only complex 1 is analyzed here. Single-crystal X-ray diffraction analysis reveals that 1 belongs to the monoclinic with space group of P21/c, 21 axial and contains a dinuclear copper complex. The dinuclear copper complex is formed by two Cu(II) ions, one bdhc ligand, one methanol terminal ligand, one nitrate and two DMF terminal ligands (Fig. 1). The Cu1 ion is in a distorted tetragonal pyramid geometry coordinated by one terminal DMF molecule (Cu1-O5, 1.958(3) Å), one oxygen atom from nitrate (Cu1-O5, 2.530(4) Å) and one oxygen and two nitrogen atoms from bdhc ligand (Cu1-O5, 1.889(4) Å), Cu1-N1, 1.950(4) Å), Cu1-N3, 1.995(4) Å) while O9 atom is in the apical position. The Cu2 is also in a distorted tetragonal pyramid geometry coordinated by one terminal DMF molecule (Cu2-O4, 1.953 (3) Å), one oxygen atom from methanol molecule (Cu2-O6, 2.435 (4) Å) and two oxygen and one nitrogen atoms from bdhc ligand (Cu2-O2, 2.435(4) Å), Cu2-O3, 1.878(4) Å), Cu2-N4, 1.942(4) Å) while O6 atom is in the apical position. It must be note that Cu1 and Cu2 exist obvious John-teller effect [50,51]. It must be point out that bdhc ligand exists as a tri-anion and displays a l:g1: g1: g1: g1: g1: g1 coordination mode (Scheme 1), it is interesting to note that such a coordination mode has not been reported until
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H.-Y. Zhang et al. / Inorganica Chimica Acta 453 (2016) 507–515 Table 1 Crystal data and structure refinement for complexes 1–5.
a b
Compound
1
2
3
4
5
Formule. Form. weight Crystal system Space group a/Å b/Å c/Å a/ o b/o c/o V/Å3 Z F(0 0 0) Dcal./g cm3 l/mm1 h range/o Ref. coll./unique Rint Completeness Parameters GOOF R1 [I P 2r(I)]a,b wR2 (all data)a,b Residues/e Å3
C22H25Br4Cu2N7O9 977.19 Monoclinic P21/c 17.913 (1) 9.178 (1) 20.920 (1) 90.00 107.72 (1) 90.00 3276.0 (2) 4 1904 1.983 6.234 3.01–25.01 5714/4119 0.0296 99.2 378 1.020 0.0430 0.1074 1.135,1.714
C23H27Br4Cu2N7O9 992.24 Monoclinic P21/c 17.915 (1) 9.179 (2) 20.930 (1) 90.00 107.71 (3) 90.00 3278.8 (1) 4 1936 2.010 6.231 3.44–25.01 5744/4402 0.0246 99.6 411 1.002 0.0347 0.0781 0.595, 1.282
C23H27Cl4Cu2N7 O9 814.42 Monoclinic P21/c 17.494 (1) 9.144 (1) 20.752 (1) 90.00 107.28(1) 90.00 3169.9 (1) 4 1644 1.706 1.739 2.87–25.10 5622/4632 0.0212 99.7 412 1.009 0.0351 0.0865 0.334, 0.729
C22H25Cl4Cu2N7O9 800.37 Monoclinic P21/n 19.171 (1) 9.311 (1) 19.288 (1) 90.00 116.11 (1) 90.00 3091.5 (2) 4 1616 1.720 1.782 2.96–25.00 5444/4508 0.0190 99.8 405 1.007 0.0298 0.0719 0.292, 0.273
C21H27Br2Cu2N7O10 824.40 Monoclinic P21/c 6.410 (1) 24.053 (1) 18.815 (1) 90.00 93.39 (1) 90.00 2895.7 (2) 4 1640 1.891 4.287 3.18–25.00 5104/3687 0.0303 99.6 386 1.006 0.0422 0.0894 0.632, 0.586
R1 = R||Fo||Fc||/R|Fo|. wR2 = [Rw(|F2o||F2c |)2/Rw(|F2o|)2]1/2.
Table 2 Metal–Ligand Bond Lengths (Å) and Angles (deg) in Complex 1–5. Complexes
1
2
3
4
5
Cu1–O1 Cu1–N1 Cu1–O5 Cu1–N3 Cu1–O9 Cu2–O3 Cu2–N4 Cu2–O4 Cu2–O2 Cu2–O6 Cu1 Cu2 O1–Cu1–N1 O1–Cu1–O5 N1–Cu1–O5 O1–Cu1–N3 N1–Cu1–N3 O5–Cu1–N3 O3–Cu2–N4 O3–Cu2–O4 N4–Cu2–O4 O3–Cu2–O2 N4–Cu2–O2 O4–Cu2–O2 O3–Cu2–O6 N4–Cu2–O6 O4–Cu2–O6 O2–Cu2 O6
1.889(4) 1.950(4) 1.958(3) 1.995(4) 2.530(4) 1.878(4) 1.942(4) 1.953(3) 1.958(4) 2.435(4) 4.791(1) 91.4(2) 87.8(2) 176.8(2) 171.4(2) 81.0(2) 99.5(2) 94.4(2) 93.3(2) 166.7(2) 171.2(2) 81.2(2) 89.7(2) 92.9(2) 92.6(2) 97.8(2) 94.9(2)
1.887(2) 1.951(2) 1.957(2) 1.990(2) 2.537(2) 1.875(2) 1.942(2) 1.947(2) 1.956(2) 2.436(2) 4.972(1) 91.4(1) 88.0(1) 176.8(1) 171.4(1) 81.1(1) 99.3(1) 94.0(1) 93.3(1) 167.0(1) 171.5(1) 81.7(1) 89.5(1) 92.6(1) 92.4(1) 97.9(1) 95.0(1)
1.887(2) 1.953(2) 1.964(2) 1.985(2) 2.539(2) 1.883(2) 1.940(2) 1.946(2) 1.957(2) 2.435(2) 4.791(1) 91.3(1) 87.9(1) 176.7(1) 171.5(1) 81.3(1) 99.2(1) 94.2(1) 93.6(1) 166.1(1) 172.1(1) 81.5(1) 89.4(1) 92.2(1) 93.4(1) 97.9(1) 94.6(1)
1.886(2) 1.951(2) 1.961(2) 1.986(2) 2.551(2) 1.870(2) 1.943(2) 1.951(2) 1.947(2) 2.386(2) 4.784(1) 91.2(1) 88.4(1) 176.2(1) 171.2(1) 81.1(1) 99.0(1) 94.2(1) 92.6(1) 166.7(1) 171.5(1) 81.7(1) 90.0(1) 91.4(1) 93.0(1) 98.3(1) 96.3(1)
1.881(3) 1.937(4) 1.960(3) 1.979(3) / 1.895(3) 1.949(4) 1.973(3) 1.936(3) 2.283(4) 4.792(1) 91.5(1) 88.9(1) 173.7(1) 171.9(1) 81.3(1) 98.7(1) 93.6(1) 90.0(1) 169.5(1) 169.3(1) 81.8(1) 93.0(1) 92.5(1) 99.0(1) 90.7(1) 97.7(1)
today. Intramolecular, the Cu1 Cu2 distance of 1–4 are 4.791 (1) Å, 4.972(1) Å, 4.791(1) Å, 4.784(1) Å, respectively. It must be note that the dimer of 1 was constructed through double weak Cu N interaction (Cu1 N3i, 3.359 Å, symmetry code: (i) 2 x, y, 1 z). It is interesting to note that the dimer exist p p interaction between bdhc ligands while the p pi distance is 3.421 Å (symmetry code: (i) 2 x, y, 1 z, Fig. S1). The dimer further constructs a 1D supramolecular chain through N-H O hydrogen bonds (N2-H2 O8vii, 2.877(1) Å, symmetry code: (vii) 2 x, 1 y, 1 z, Fig. 2). The 1D supramolecular chain was formed 3D network through Br Br interaction (Br2 Br2ii,
3.538 Å; Br2 Br2iii, 3.880 Å; Br3 Br4iv, 3.880 Å; symmetry code: (ii) 3 x, 1 y, 1 z; (iii) 1 + x, y, z; (iv) 1 x, 0.5 + y, 0.5 z.) [52] and weak C-H Br hydrogen bonds (C20-H20A Br2v, 3.720 Å; C22-H22C Br4vi, 3.843 Å, symmetry code: (v) 1 + x, y, z; (vi) x, 1 + y, z.) and C-H O hydrogen bond (C6-H6 O6vii, 3.431 Å, symmetry code: (vii) 2 x, 1 y, 1 z.) (Fig. S2). 3.1.2. [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) The structure of 5 is different from 1 to 4, because the NO 3 ion is free in 5 but in other four complexes are coordinated with Cu1 ion (Fig. 3). The dinuclear copper complex is formed by two Cu(II) ions,
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Fig. 1. Crystal structures of 1–4.
3.819 Å; symmetry code: (iv) 2 x, 0.5 + y, 0.5 z) [52], N-H O hydrogen bond (N2-H2 O6ii, 2.759Å) and O-H O hydrogen bonds (O10-H10B O10v, symmetry code: (v) x 1, y, z), and C-H O hydrogen bonds (C17-H17 O7iv, 3.095 Å; C19-H19 O8ii, 3.245 Å. Fig. S4).
3.2. Hirshfeld surface analysis Scheme 1. Coordination mode of the schiff base ligands.
one bbhc ligand, two DMF terminal ligands, one coordination water molecule, one counter anion nitrate and one lattice water molecule. The Cu1 ion is coordinated in a slightly distorted square–planar geometry by two nitrogen atoms and one oxygen atom from a bbhc ligand (Cu1–O1, 1.881(3) Å, Cu1–N1, 1.937 (4) Å, Cu1–N3, 1.979(3) Å) and one oxygen atom form DMF molecule (Cu1–O5, 1.960(3) Å). The coordination geometry of the Cu2 ion in 5 is similar to Cu2 of complexes 1–4. It must be note that the intramolecular, the Cu1 Cu2 distance of 5 is 4.792(1) Å which is the same as Cu1 Cu2 distance of 1–4. It is interesting to note that the 1-D chain was constructed by weak Cu O interaction (Cu1 O3i, 3.081 Å, symmetry code: (i) 1 + x, y, z, Fig. S3). The 1-D chain further formed double chain through strong O-H O hydrogen bonds (O6-H6AC O3ii, 2.772(4) Å, O6-H6AC O6iii, 2.772(4) Å, symmetry code: (ii) x, 1 y, 1 z, (ii) 1 x, 1 y, 1 z). It must be note that the double chains were formed 3-D supramolecular network through BrBr interaction (Br1Br2iv,
Hirshfeld surface is a useful tool for describing the surface characteristics of the molecules. The molecular Hirshfeld surface of the present five compounds were shown in Fig. 4. The dnorm surface is used to identify the very close intermolecular interactions. The dnorm values are mapped onto the Hirshfeld surface with a three-color scheme: where red regions correspond to that the closer intermolecular contacts than rvdW (van der Waals (vdW) radii); the blue regions correspond to longer intermolecular contacts than rvdW; and the white regions correspond to the distance of intermolecular contacts is exactly the rvdW. The deep red regions on dnorm surface indicate the close-contact interactions, which are mainly responsible for the significant hydrogen bonding contacts. For the present five complexes, these deep red regions are indicative of short contacts of N H, and O H interactions, which correspond to the N-H O and O-H O hydrogen bonds. (Fig. 4, Table 3). The small red regions on the dnorm surfaces are corresponding to the significant of C-H Br interactions. 2D fingerprint plots are an important supplement for the Hirshfeld surface. It is quantitatively describe the nature and type of intermolecular interactions between the molecules inside the crystals. The 2D fingerprint plots can be decomposed to highlight the
Fig. 2. 1D chain of 1.
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3.3. UV–vis spectrum The UV–vis spectra of complexes 1–5 are studied in the ranges 200–800 nm in DMF solution (3 105 M) (Fig. 6). Generally, for some Schiff bases derivatives from salicylaldehyde, there are no absorption bands were observed above 400 nm in polar and nonpolar solvents [53]. It must be note that a significant broad band was observed at 407, 414, 424, 415 and 415 nm for 1–5, respectively. The results indicated that the five molecules exist ligandto-metal-charge-transfer (LMCT) [54,55]. In addition, the UV–vis spectra of 1–5 showed another peak at 273 nm, 270 nm, 268 nm, 269 nm and 270 nm, respectively and it can be assigned to p ? p⁄ overlaps with charge transfer. According to the UV–vis spectra of 1–5, the complexes 1–5 showed two same peaks at 415 nm, and 270 nm. The results were consistent with structural analysis results. Fig. 3. Crystal structure of 5.
particular close contacts between atoms pair. The main intermolecular interactions of the five compounds is H H contacts which reflected in the middle of the scattered point of the 2D fingerprint plots (the percentage of H H contacts of 1–5 is 22.7%, 25.5%, 26.4%, 23.3% and 29.5%, respectively). The X H (X = Cl, Br) interaction is one of the most significant contacts for these compounds. For complex 1, the X H interactions are represented by a spike in the bottom left (donor) area of the fingerprint plot (Fig. 5), the H X interactions are represented by a spike in the bottom right (acceptor) region of the fingerprint plot. So we can infer that there are significant C-H X (X = Cl, Br) interactions are observed in both the compounds (the percentage of X H contacts of 1–5 is 20.4%, 24.0%, 23.9%, 22.0% and 13.0%, respectively). The other one significant interaction for these compounds is O H contacts. It is reflected in the 2D fingerprint plot and seems like the gums, which correspond to the large red regions of the dnorm surface. The percentage of O H contacts of 1–5 is 21.0%, 19.2%, 19.2%, 23.0% and 25.5%, respectively. Apart from those above, the presence of C H, C O, X X (X = Cl, Br) and other contacts are observed, and they are all summarized in Table 3.
3.4. Fluorescence properties In this study, fluorescence properties of the 1–5 and three ligands have been investigated at room temperature. Solid state luminescent properties of the free H3bchc, H3bbhc, H3bdhc ligands and five complexes 1–5 have been investigated at room temperature (Fig. 7). Upon photoexcitation at 380 nm, H3bchc, H3bbhc, H3bdhc ligands exhibit a green luminescent emission band with the maximum at 561, 566,563 nm, respectively while upon photoexcitation at 416 nm, complexes 1–5 exhibit a green luminescent emission band with the maximum at 632, 632, 632, 632, 630 nm, respectively. It must be note that the luminescent emission are assigned to p-p⁄ transition fluorescent. Compared to the free H3bchc, H3bbhc, H3bdhc ligands, the 1–5 exist about 70 nm red-shifted which due to the ligand to metal charge transfer (LMCT) excited state [56,57]. Emission intensities slowly decrease from H3bchc, H3bbhc, to H3bdhc ligands. In this study, luminescent properties of 1–5 have been investigated in DMF solvent with concentration of 1 104, 5 105, 1 105, 5 106, 1 106 mol/L, respectively (Fig. 8, Figs. S5–S8). Upon photoexcitation at 416 nm, complexes 1–5 exhibit a blue luminescent with the maximum at around 495 nm predominantly assigned to p ? p* transition fluorescent emission.
Fig. 4. Hirshfeld surface mapped with dnorm for complex 1–5.
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Table 3 The percentages of contacts between different element pairs contributed to the total Hirshfeld Surface area of molecules (X = Cl, Br). Complexes
H–H
C–H
O–H
X–H
C–C
C–O
Br–Br
Other
1 2 3 4 5
22.7 25.5 26.4 23.3 29.5
8.1 8.2 8.7 7.7 10.4
21.0 19.2 19.2 23.0 25.5
20.4 24.0 23.9 22.0 13.0
3.0 3.2 3.2 3.4 1.6
3.3 2.5 2.6 3.1 2.9
3.8 3.7 2.9 2.5 1.3
17.7 13.7 13.1 15.0 15.8
Fig. 5. Fingerprint plots of 1–5: Full (1) and resolved into X H (2), C H (3), H H (4) and O H (5) contacts showing the percentages of contacts contributed to the total Hirshfeld Surface area of molecules.
Compared to the emission intensity of the fluorescent in five different concentration solution, the fluorescence intensity of the complexes 1–5 were enhanced when the concentration of the of the solution were reduced [58,59]. The result indicates that fluores-
cence concentration self-quenching effect was observed in the solution of 1–5. Compared to the solid state luminescent of the complexes 1–5, with 135 nm blue-shifted, the blue-shifted is assigned to the aggregation induced emission [60].
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3.5. In vitro antitumor
Fig. 6. UV–vis spectra of complexes 1–5 together in DMF medium [concentration: 3 105 (M)].
Using the MTT method, the anti-proliferative activity of complexes 1–5 was evaluated against a panel of human tumor cells including BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SK-OV-3 and normal human liver HL-7702 cells. Each compound was prepared as 2.0 mM DMSO stock solution before they were diluted by PBS buffer to 20 lM aqueous solutions (containing 2% DMSO). As shown in Table 4, complexes 1–5 exhibited the cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SKOV-3. In contrast, complex 3 showed higher inhibitory rates against Hep-G2, NCI-H460, T-24, MGC-803, A549 and SK-OV-3 cells than other complexes. The inhibitory rates of complex 1 and 5 against BEL-740 and HepG2 are all higher than 30%. For T-24, MGC-803, A549, the inhibitory rates of complex 1, 2, 3, 5 are higher than 30%. All the complexes exhibited lower cytotoxicity against HL-7702 than that of cisplatin. The in vitro antitumor activity of complexes 1–5 was further quantified by determining the corresponding IC50 levels. As shown in Fig. 9 and Table 5, complexes 1–5 exhibited high IC50 values against BEL-7404, HepG2, NCI-H460, MGC-803 cells. Compared with the case of normal liver cell HL-7702, the cytotoxicity of complexes 2 and 4 toward the BEL-7404 tumor cells is enhanced by 4.5 and 3.1 times, respectively, which indicating the selectivity of complexes 2 and 4 on BEL-7404. Furthermore, in the cases of T-24, A549, SK-OV-3 cells, complex 3 displayed stronger cytotoxicity than cisplatin, with the IC50 values of 9.41 lM, 12.96 lM, 24.09 lM, respectively. Among them, T-24 cells showed the highest sensitivity to complex 3 with IC50 value of 9.41 ± 0.49 lM, which increased approximately 3-fold comparing with the cisplatin. Complex 3 may be a good candidate for anti-cancer drugs due to its high selectivity against T-24, A549 and SK-OV-3 cells. Compare to complexes 1–5, the bchc ligand in 3 and 4 has great capacity of electron-withdrawing substituent. On the other hand, at the apical position, ethanol molecules in 2 and 3 are easier to leave the complexes than methanol and water molecules in 1, 4, 5. As result, complexes 2 and 3 easier to become planar molecules than complexes 1, 4, 5. These two factors maybe result that complex 3 has good antitumor activity. 3.6. Magnetic property of 1
Fig. 7. Emission spectra of the 1–5 and the H3bchc, H3bbhc, H3bdhc ligands in a solidstate at room temperature.
Fig. 8. Solvent luminescence spectrum of the complex 1.
The magnetic susceptibilities of 1 were measured from crushed single crystalline samples under an applied field of 1 kOe for 1 at temperature range of 2–300 K (Fig. 10). The spin–orbit coupling of the two Cu(II) ions gives rise to a vMT product of 0.53 cm3 Kmol1 at room temperature. The vMT value at room temperature is slightly less than the spin-only value expected for two isolated Cu(II) ions that is 0.75 cm3Kmol1 with SCu = 1/2 and gCu = 2.0 [61]. It must be noted that the observed value of 1 is also slightly less than what was obtained for [Cu2(bpad)2(Hp)2]n (Hbpad = N3-benzoylpyridine-2-carboxamidrazone, H2p = phthalic acid) (0.875 cm3Kmol1) [61], [Cu2(l-Cl)2Cl2(pbba)2] (pbba = N-((pyridin-2-yl)benzylidene)benzylamine) (0.875 cm3Kmol1) [62]. With decrease in T, vMT value reduces to a minimum of 0.013 cm3Kmol1 at 50 K. Under 50 K, vMT of 1 remains constant till 2 K. To fit and interpret magnetic susceptibility data of 1, it is necessary to find all possible magnetic pathways. The intramolecular antiferromagnetic interaction in 1 is as expected keeping in mind that the exchange pathway involved is provided by one dinitrogen bridge between two Cu(II) ions of the dinuclear unit. Consequently, the dimeric nature of the 1 can be easily simplified to a Cu(II) dimer skeleton as schematized. Keeping the above considerations in mind, to calculate the magnetic exchange interaction (J)
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Table 4 The inhibitory effect on different cells of complexes 1–5(%). Complex
BEL-740
HepG2
NCI-H460
T-24
MGC-803
A549
SK-OV-3
HL-7702
1 2 3 4 5 Cisplatin
33.45 ± 1.54 45.71 ± 1.42 19.85 ± 0.16 35.47 ± 0.15 22.90 ± 3.62 55.15 ± 1.18
37.66 ± 1.41 20.38 ± 2.58 53.82 ± 1.93 38.96 ± 2.39 22.78 ± 1.42 60.63 ± 0.99
24.75 ± 1.79 34.88 ± 1.96 44.15 ± 2.73 35.79 ± 1.43 30.08 ± 2.46 50.88 ± 3.69
30.71 ± 1.38 30.72 ± 2.39 56.45 ± 1.20 28.45 ± 1.50 30.83 ± 3.39 37.38 ± 3.39
25.67 ± 1.76 41.87 ± 2.94 59.35 ± 2.12 47.38 ± 1.54 50.38 ± 3.87 71.35 ± 1.46
39.29 ± 1.52 35.17 ± 2.16 53.39 ± 4.37 13.94 ± 1.25 34.96 ± 3.19 51.14 ± 3.43
28.24 ± 1.78 36.06 ± 0.66 41.91 ± 2.02 26.94 ± 2.63 34.65 ± 1.01 46.56 ± 0.92
45.59 ± 1.74 15.38 ± 1.34 32.93 ± 1.59 17.97 ± 3.91 11.53 ± 0.81 73.58 ± 2.30
Fig. 9. IC50 (lM) values of complex 1–5 and cisplatin towards eight selected cell lines for 48 h.
Table 5 The IC50a on different cells of complexes 1–5 (lM).
a
Complexes
BEL-7404
HepG2
NCI-H460
T-24
MGC-803
A549
SK-OV-3
HL-7702
1 2 3 4 5 Cisplatin
31.68 ± 2.37 26.67 ± 0.39 46.04 ± 0.65 32.85 ± 2.79 112.47 ± 1.53 12.41 ± 0.38
36.41 ± 1.81 103.96 ± 2.25 13.04 ± 0.75 35.48 ± 0.88 56.04 ± 1.48 9.48 ± 0.35
39.42 ± 1.02 27.31 ± 0.51 22.86 ± 0.14 35.67 ± 1.52 32.22 ± 1.78 18.89 ± 1.02
34.22 ± 1.18 28.44 ± 0.60 9.41 ± 0.49 39.19 ± 1.16 35.41 ± 0.49 28.07 ± 1.88
78.07 ± 1.38 26.78 ± 1.02 8.29 ± 0.60 18.43 ± 1.53 13.76 ± 1.01 5.43 ± 0.45
78.07 ± 1.38 65.09 ± 1.65 12.96 ± 1.30 92.96 ± 1.29 27.35 ± 1.32 17.35 ± 1.34
57.35 ± 1.33 38.89 ± 1.49 24.09 ± 1.01 44.53 ± 1.58 34.53 ± 2.59 26.77 ± 0.89
36.77 ± 0.91 119.44 ± 1.42 37.99 ± 3.02 103.71 ± 1.50 128.30 ± 2.31 5.63 ± 0.32
IC50 values are presented as the mean ± SD (standard error of the mean) from five independent experiments.
between the copper centers in 1, the magnetic data was fitted to be modified Bleaney-Bowers equation expression for two interacting Cu(II) ions (S = 1/2) with isotropic spin Hamiltonian in the form ^ ¼ J ^ H S1 ^ S2 and it is given by Eq. (1). The best curve fitting gave 1
g = 1.99, J1 = -85.1 cm1, and R = 2.86 104. The R represents agreement factor and it is defined in Eq. (2). The negative J value represent obvious antiferromagnetic coupling between two Cu(II) centers in 1.
vM ¼ R¼
2Ng 2 b2 1 3 þ e2J=kT kT
X ðvm TÞexp ðvm TÞcal 2 ðvm TÞcal
ð1Þ ð2Þ
4. Conclusion Fig. 10. Plot of vMT and vM vs T measured in a 1000 Oe field for 1. The solid lines represent the best fits of data as described in the text.
Five new dinuclear copper complexes have been synthesized by modulating substituent of the schiff base ligands. The results of
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vitro antitumor activity reveal that 3 exhibited a high apoptosisinduced ability against T-24, A549, SK-OV-3. Hirshfeld surface and fingerprint plot analysis of 1–5 revealed that the close contacts of these five complexes were dominated by H H, X H (X = Cl, Br), O H and C H interactions. There are significant N-H O, O-H O and C-H X (X = Cl, Br) interactions are observed in all the five compounds. The fluorescence indicates that fluorescence concentration self-quenching effect was observed in the solution of 1–5. On the other hand, magnetic studies reveal that there is antiferromagnetic interactions between two Cu(II) ions. Acknowledgments This work was supported by the National Nature Science Foundation of China (No. 21161006), the Nature Science Foundation of Guangxi Province of China (No. 2015GXNSFAA139031); Program for the scientific research and technology development plan of Guilin (No.20150133-5) and Program of the first session backbone teacher of Guangxi of China. Appendix A. Supplementary data Crystallographic data (excluding structure factors) for 1–5 in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC 1472827–1472831. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: 44 1223 336033, e-mail: [email protected]). Electronic supplementary information (ESI) available: [Dinmmer of 1 (Fig. S1), Packing diagram of 1. (Fig. S2), 1-D chain of 5 (Fig. S3), Packing diagram of 5 (Fig. S4). Solution state emission spectra of complexes 2–5 at room temperature (Figs. S5–S8)]. Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ica.2016.09.013. References [1] S.H. Zhang, R.X. Zhao, G. Li, H.Y. Zhang, C.L. Zhang, G. Muller, RSC Adv. 4 (2014) 54837–54846. [2] A.W. Addison, T.N. Rao, J. Reedijk, J. van Rijn, G.C. Verschoor, J. Chem. Soc., Dalton Trans. (1984) 1349–1356. [3] S.T. Meally, C. McDonald, G. Karotsis, G.S. Papaefstathiou, E.K. Brechin, P.W. Dunne, L.F. Jones, Dalton Trans. 39 (2010) 4809–4816. [4] S. Demir, A. Güder, T.K. Yazıcılar, S. Çag˘lar, O. Büyükgüngör, Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 150 (2015) 821–828. [5] Y. Jia, J. Li, Chem. Rev. 115 (2014) 1597–1621. [6] P. Przybylski, A. Huczynski, K. Pyta, B. Brzezinski, F. Bartl, Curr. Org. Chem. 13 (2009) 124–148. [7] C. Yu, L. Jiao, P. Zhang, Z. Feng, C. Cheng, Y. Wei, E. Hao, Org. Lett. 16 (2014) 3048–3051. [8] M.D. Peterson, R.J. Holbrook, T.J. Meade, E.A. Weiss, J. Am. Chem. Soc. 135 (2013) 13162–13167. [9] L. Li, X. Hua, Y. Huang, X. Yang, C. Wang, J. Du, Synth. React. Inorg., Met.-Org., Nano-Met. Chem. 44 (2014) 291–294. [10] R.A. Kumar, M. Arivanandhan, Y. Hayakawa, Prog. Cryst. Growth Charact. Mater. 59 (2013) 113–132. [11] J.B. Pelayo-Vázquez, F.J. González, M.A. Leyva, M. Campos, L.A. Torres, M.J. Rosales-Hoz, J. Organomet. Chem. 716 (2012) 289–293. [12] T. Balic´, B. Markovic´, M. Medvidovic´-Kosanovic´, J. Mol. Struct. 1084 (2015) 82– 88. [13] Y. Xiao, Y. Qin, M. Yi, Y. Zhu, J. Clust, Science (2016), http://dx.doi.org/10.1007/ s10876-016-1059-y. [14] P.A. Vigato, V. Peruzzo, S. Tamburini, Coord. Chem. Rev. 256 (2012) 953–1114. [15] R. Sessoli, D. Gatteschi, Angew. Chem. Int. Ed. 42 (2003) 268–297.
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Research paper
Five novel dinuclear copper(II) complexes: Crystal structures, properties, Hirshfeld surface analysis and vitro antitumor activity study Hai-Yang Zhang, Wei Wang, Hao Chen, Shu-Hua Zhang ⇑, Yan Li ⇑ College of Chemistry and Bioengineering (Guangxi Key Laboratory of Electrochemical and Magneto-chemical Functional Materials), Guilin University of Technology, Guilin 541004, People’s Republic of China
a r t i c l e
i n f o
Article history: Received 18 April 2016 Received in revised form 26 August 2016 Accepted 8 September 2016 Available online 13 September 2016 Keywords: N,O ligand Dinuclear copper Crystal structure Antitumor activity Self-quenching effect
a b s t r a c t Five dinuclear copper(II) complexes have been synthesized with three kinds of Schiff bases and Cu (NO3)2H2O in different solvent systems: [Cu2(bdhc)(CH3OH)(NO3)(dmf)2] (1), [Cu2(bdhc)(CH3CH2OH) (NO3)(dmf)2] (2) [Cu2(bchc)(CH3CH2OH)(NO3)(dmf)2] (3), [Cu2(bchc)(CH3OH)(NO3)(dmf)2] (4), [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) (H3bdhc is 1,5-bis(3,5-dibromosalicylidene)-carbohydrazide, H3bchc is 1,5-bis(3,5-dichlorosalicylidene)-carbohydrazide, H3bbhc is 1,5-bis(5-bromosalicylidene)-carbohydrazide). All the compounds were characterized by IR spectroscopy, Element analysis and X-ray single-crystal diffraction. The anti-proliferative activity of 1–5 was evaluated against a panel of human tumor cells while 3 exhibited a high antitumor activity against T-24, A549, SK-OV-3 and MGC-803. A detailed analysis of Hirshfeld surface and 2D fingerprint plot revealed that 1–5 were supported mainly by H H, C-H X (X = Cl, Br) and O H intermolecular interactions. Fluorescence properties indicate that all the complexes exist fluorescence concentration self-quenching effect. The magnetic properties of 1 from 2 to 300 K are also discussed. Ó 2016 Elsevier B.V. All rights reserved.
1. Introduction To date, various molecules bearing functional groups have been used in organic and inorganic crystal engineering for designing and synthesis of novel compounds with expectation properties [1–3]. It has been reported that most Schiff bases and its derivative ligands possess versatile bonding modes and they can easily coordinate with metal ions. Moreover, many Schiff base complexes possess fascinating structures and functional applications in medical [4–8], optical [9,10], electrochemical [11,12], magnetic [13–19], luminescence [20–23] and catalytic materials [24–26]. Great efforts have been devoted to the synthesis of novel Schiff bases and its derivative ligands coordinated with metal ions. The exploration of molecular crystal structures through the aspect of intermolecular interactions have aroused much attention recent years [27,28]. As a powerful tool for describing molecular crystal structures, Hirshfeld surfaces analysis is the main approach to identifying the common features of crystals [29–31]. Cancer chemotherapy with platinum drugs has been used since the discovery of cisplatin’s anti-proliferate properties by Rosenberg et al. [32]. Because there are lots of side effects of the platinum⇑ Corresponding authors. E-mail address: [email protected] (S.-H. Zhang). http://dx.doi.org/10.1016/j.ica.2016.09.013 0020-1693/Ó 2016 Elsevier B.V. All rights reserved.
based anticancer drugs, great efforts have been devoted to the synthesis of non-platinum metal-based drugs in order to decrease the side effects [33–35]. The biological chemistry of copper complexes has undergone tremendous research and development in recent years with the increasing number of copper complexes with medicinal applications [36–42]. Many Schiff bases have been utilized in medical materials due to their excellent biological properties. So the medical research of copper(II) complexes derived from Schiff base ligands has been proved as a attractive field [43–46]. In this context, five copper (II) complexes were synthesized by reacting Cu(NO3)2 and three Schiff base ligands (H2bdhc, H2bchc and H2bbhc) in the test tube. Using the MTT method, the anti-proliferative activity of complexes 1–5 was evaluated against a panel of human tumor cells including BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SK-OV-3 and normal human liver HL-7702 cells. 2. Experimental section 2.1. Materials and physical measurements All chemicals were commercially available and used as received without purification. Elemental analyses (CHN) were performed using an PE 2400 series II elemental analyzer. FT–IR spectra were
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recorded from KBr pellets in the ranges 4000–400 cm1 on a BioRad FTS-7 spectrophotometer. The crystal structures were determined on a Agilent G8910A CCD diffractometer using the SHELXS-97 and SHELXL-97 for structure solution and refinement, correspondingly. UV–vis spectra were recorded in the range 200– 800 nm on a UV-2450 spectrophotometer. Luminescence spectra were performed on a Hitachi F-4600 fluorescence spectrophotometer at room temperature. Magnetic measurements were carried out with a Quantum Design PPMS model 600 magnetometer to 5 T for 1. 2.2. Syntheses 2.2.1. [Cu2(bdhc)(CH3OH)(NO3)(dmf)2] (1) A mixture of H3bdhc (0.5 mmol, 0.313 g), DMF (3 mL), CH2Cl2 (2 mL) was transferred to a 15 150 mm test tube. Methanol solution (5 mL) of Cu(NO3)2H2O(0.5 mmol, 0.121 g) was slowly poured into the test tube and then sealed it. Dark green crystals of 1 were collected by filtration after 8 days, and washed with methanol (10 mL 3), then dried in air (yield: 0.133 g, ca. 54.5% based on Cu(NO3)2H2O). Elemental Analysis (%) For 1: C22H25Br4Cu2N7O9 (Mr = 977.19 g/mol), Calc.: C, 27.04; H, 2.59; N, 10.03. Found: C, 26.98; H, 2.54; N, 10.09. IR data for 1 (KBr, cm1) 3429 m, 2928 w, 2366 m, 1642 s, 1604 s, 1496 m, 1434 m, 1388 s, 1219 w, 1157 m, 865 w. 2.2.2. [Cu2(bdhc)(CH3CH2OH)(NO3)(dmf)2] (2) Complex 2 was prepared in a similar way to 1, except that the methanol was replaced by ethanol. Dark Green crystals of 2 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.127 g, ca. 51.2% based on Cu(NO3)2H2O). Elemental Analysis (%) For 2: C23H27Br4 Cu2N7O9 (Mr = 992.24 g/mol), Calc.: C, 27.84; H, 2.74; N, 9.88. Found: C, 27.80; H, 2.79; N, 9.92. IR data for 2 (KBr, cm1) 3413 m, 3121 m, 2335 w, 1650 s, 1612 s, 1496 s, 1434 m, 1381 s, 1211 w, 1157 m, 856 w. 2.2.3. [Cu2(bchc)(CH3CH2OH)(NO3)(dmf)2] (3) Complex 3 was prepared in a similar way to 2, except that the H3bdhc was replaced by H3bchc. Dark Green crystals of 3 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.131 g, ca. 52.7% based on Cu(NO3)2H2O). Elemental Analysis (%) for 3: C23H27Cl4Cu2N7O9 (Mr. = 814.42 g/mol), Calc.: C, 33.92; H, 3.34; N, 12.03. Found: C, 33.90; H, 3.38; N, 12.08. IR data for 3 (KBr, cm1) 3425 w, 3217 w, 2932 w, 1644 s, 1605 s, 1497 s, 1428 s, 1389 s, 1212 w, 1173 m, 872 w. 2.2.4. [Cu2(bchc)(CH3OH) (NO3)(dmf)2] (4) Complex 4 was prepared in a similar way to 3, except that the ethanol was replaced by methanol. Dark Green crystals of 4 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.098 g, ca. 49.4% based on Cu(NO3)2H2O). Elemental Analysis (%) for 4: C22H25Cl4Cu2N7O9 (Mr. = 800.37 g/mol), Calc.: C, 33.05; H, 3.15; N, 12.25. Found: C, 32.99; H, 3.14; N, 12.28. IR data for 4 (KBr, cm1) 3413 m, 3128 m, 2343 w, 1650 s, 1596 s, 1496 s, 1427 s, 1381 s, 1295 w, 1181 m, 865 w. 2.2.5. [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) Complex 5 was prepared in a similar way to 1, except that the H3bdhc was replaced by H3bbhc. Dark Green crystals of 5 were collected by filtration, washed with ethanol (10 mL 3) and dried in air (yield: 0.098 g, ca. 48.3% based on Cu(NO3)2H2O). Elemental Analysis (%) for 5: C21H26Br2Cu2N7O10 (Mr. = 823.39 g/mol), Calc.: C, 30.60; H, 3.30; N, 11.89. Found: C, 30.58; H, 3.26; N, 11.92. IR data for 5 (KBr, cm1) 3409 m, 3231 w, 2930 w, 1639 s, 1609 s, 1501 s, 1423 m, 1377 s, 1176 w, 1122 m, 821 w.
2.3. Crystal structure determination The diffraction data were collected on an Agilent G8910A CCD diffractometer with graphite monochromated Mo-Ka radiation (k = 0.71073 Å), using the x-h scan mode in the ranges 3.01° 6 h 6 25.00° (1), 3.44° 6 h 6 25.01° (2), 2.87° 6 h 6 25.10° (3), 2.90° 6 h 6 25.10° (4), 3.18° 6 h 6 25.00° (5). Raw frame data were integrated with the SAINT program. The structures were solved by direct methods using SHELXS-97 and refined by full matrix least-squares on F2 using SHELXS-97 [47]. An empirical absorption correction was applied with the program SADABS [47]. All non-hydrogen atoms were refined anisotropically. All hydrogen atoms were positioned geometrically and refined as riding. Calculations and graphics were performed with SHELXTL [47]. The anisotropic displacement parameters of the atoms C22, C23 were restrained to be identical with a standard uncertainty of 0.01 Å2 in 1. The highest peak with 1.714 eÅ3 of 1 and 1.282 eÅ3 of 2 in the residual electron density is located 0.74 Å from atom H22a, 0.83 Å from atom H22a, respectively. The detailed crystallographic data and structure refinement parameters are summarized in Table 1. Selected bond lengths and angles for complexes 1–5 are given in Table 2.
2.4. Hirshfeld surface calculations of 1–5 Molecular Hirshfeld surface calculations were performed by using the CrystalExplorer program[48]. When the CIF file of 1 are read into the CrystalExplorer program, all bond lengths to hydrogen were automatically modified to typical standard neutron values (C-H = 1.083 Å, N-H = 1.009 Å and O-H = 0.983 Å) [49]. In this study, all the Hirshfeld surfaces were generated using a high(standard) surface resolution. The 3D dnorm surfaces were mapped by using a fixed color scale of 0.76 (red) to 2.4 (blue). The 2D fingerprint plots were displayed by using the standard 0.4–2.6 Å view with the de and di distance scales displayed on the graph axes.
3. Results and discussion 3.1. structural description 3.1.1. Complexes 1–4 The structures of 1–4 are strikingly similar except the terminal ligands and the halogen substituents of the Schiff base ligands are different (Fig. 1). Therefore only complex 1 is analyzed here. Single-crystal X-ray diffraction analysis reveals that 1 belongs to the monoclinic with space group of P21/c, 21 axial and contains a dinuclear copper complex. The dinuclear copper complex is formed by two Cu(II) ions, one bdhc ligand, one methanol terminal ligand, one nitrate and two DMF terminal ligands (Fig. 1). The Cu1 ion is in a distorted tetragonal pyramid geometry coordinated by one terminal DMF molecule (Cu1-O5, 1.958(3) Å), one oxygen atom from nitrate (Cu1-O5, 2.530(4) Å) and one oxygen and two nitrogen atoms from bdhc ligand (Cu1-O5, 1.889(4) Å), Cu1-N1, 1.950(4) Å), Cu1-N3, 1.995(4) Å) while O9 atom is in the apical position. The Cu2 is also in a distorted tetragonal pyramid geometry coordinated by one terminal DMF molecule (Cu2-O4, 1.953 (3) Å), one oxygen atom from methanol molecule (Cu2-O6, 2.435 (4) Å) and two oxygen and one nitrogen atoms from bdhc ligand (Cu2-O2, 2.435(4) Å), Cu2-O3, 1.878(4) Å), Cu2-N4, 1.942(4) Å) while O6 atom is in the apical position. It must be note that Cu1 and Cu2 exist obvious John-teller effect [50,51]. It must be point out that bdhc ligand exists as a tri-anion and displays a l:g1: g1: g1: g1: g1: g1 coordination mode (Scheme 1), it is interesting to note that such a coordination mode has not been reported until
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a b
Compound
1
2
3
4
5
Formule. Form. weight Crystal system Space group a/Å b/Å c/Å a/ o b/o c/o V/Å3 Z F(0 0 0) Dcal./g cm3 l/mm1 h range/o Ref. coll./unique Rint Completeness Parameters GOOF R1 [I P 2r(I)]a,b wR2 (all data)a,b Residues/e Å3
C22H25Br4Cu2N7O9 977.19 Monoclinic P21/c 17.913 (1) 9.178 (1) 20.920 (1) 90.00 107.72 (1) 90.00 3276.0 (2) 4 1904 1.983 6.234 3.01–25.01 5714/4119 0.0296 99.2 378 1.020 0.0430 0.1074 1.135,1.714
C23H27Br4Cu2N7O9 992.24 Monoclinic P21/c 17.915 (1) 9.179 (2) 20.930 (1) 90.00 107.71 (3) 90.00 3278.8 (1) 4 1936 2.010 6.231 3.44–25.01 5744/4402 0.0246 99.6 411 1.002 0.0347 0.0781 0.595, 1.282
C23H27Cl4Cu2N7 O9 814.42 Monoclinic P21/c 17.494 (1) 9.144 (1) 20.752 (1) 90.00 107.28(1) 90.00 3169.9 (1) 4 1644 1.706 1.739 2.87–25.10 5622/4632 0.0212 99.7 412 1.009 0.0351 0.0865 0.334, 0.729
C22H25Cl4Cu2N7O9 800.37 Monoclinic P21/n 19.171 (1) 9.311 (1) 19.288 (1) 90.00 116.11 (1) 90.00 3091.5 (2) 4 1616 1.720 1.782 2.96–25.00 5444/4508 0.0190 99.8 405 1.007 0.0298 0.0719 0.292, 0.273
C21H27Br2Cu2N7O10 824.40 Monoclinic P21/c 6.410 (1) 24.053 (1) 18.815 (1) 90.00 93.39 (1) 90.00 2895.7 (2) 4 1640 1.891 4.287 3.18–25.00 5104/3687 0.0303 99.6 386 1.006 0.0422 0.0894 0.632, 0.586
R1 = R||Fo||Fc||/R|Fo|. wR2 = [Rw(|F2o||F2c |)2/Rw(|F2o|)2]1/2.
Table 2 Metal–Ligand Bond Lengths (Å) and Angles (deg) in Complex 1–5. Complexes
1
2
3
4
5
Cu1–O1 Cu1–N1 Cu1–O5 Cu1–N3 Cu1–O9 Cu2–O3 Cu2–N4 Cu2–O4 Cu2–O2 Cu2–O6 Cu1 Cu2 O1–Cu1–N1 O1–Cu1–O5 N1–Cu1–O5 O1–Cu1–N3 N1–Cu1–N3 O5–Cu1–N3 O3–Cu2–N4 O3–Cu2–O4 N4–Cu2–O4 O3–Cu2–O2 N4–Cu2–O2 O4–Cu2–O2 O3–Cu2–O6 N4–Cu2–O6 O4–Cu2–O6 O2–Cu2 O6
1.889(4) 1.950(4) 1.958(3) 1.995(4) 2.530(4) 1.878(4) 1.942(4) 1.953(3) 1.958(4) 2.435(4) 4.791(1) 91.4(2) 87.8(2) 176.8(2) 171.4(2) 81.0(2) 99.5(2) 94.4(2) 93.3(2) 166.7(2) 171.2(2) 81.2(2) 89.7(2) 92.9(2) 92.6(2) 97.8(2) 94.9(2)
1.887(2) 1.951(2) 1.957(2) 1.990(2) 2.537(2) 1.875(2) 1.942(2) 1.947(2) 1.956(2) 2.436(2) 4.972(1) 91.4(1) 88.0(1) 176.8(1) 171.4(1) 81.1(1) 99.3(1) 94.0(1) 93.3(1) 167.0(1) 171.5(1) 81.7(1) 89.5(1) 92.6(1) 92.4(1) 97.9(1) 95.0(1)
1.887(2) 1.953(2) 1.964(2) 1.985(2) 2.539(2) 1.883(2) 1.940(2) 1.946(2) 1.957(2) 2.435(2) 4.791(1) 91.3(1) 87.9(1) 176.7(1) 171.5(1) 81.3(1) 99.2(1) 94.2(1) 93.6(1) 166.1(1) 172.1(1) 81.5(1) 89.4(1) 92.2(1) 93.4(1) 97.9(1) 94.6(1)
1.886(2) 1.951(2) 1.961(2) 1.986(2) 2.551(2) 1.870(2) 1.943(2) 1.951(2) 1.947(2) 2.386(2) 4.784(1) 91.2(1) 88.4(1) 176.2(1) 171.2(1) 81.1(1) 99.0(1) 94.2(1) 92.6(1) 166.7(1) 171.5(1) 81.7(1) 90.0(1) 91.4(1) 93.0(1) 98.3(1) 96.3(1)
1.881(3) 1.937(4) 1.960(3) 1.979(3) / 1.895(3) 1.949(4) 1.973(3) 1.936(3) 2.283(4) 4.792(1) 91.5(1) 88.9(1) 173.7(1) 171.9(1) 81.3(1) 98.7(1) 93.6(1) 90.0(1) 169.5(1) 169.3(1) 81.8(1) 93.0(1) 92.5(1) 99.0(1) 90.7(1) 97.7(1)
today. Intramolecular, the Cu1 Cu2 distance of 1–4 are 4.791 (1) Å, 4.972(1) Å, 4.791(1) Å, 4.784(1) Å, respectively. It must be note that the dimer of 1 was constructed through double weak Cu N interaction (Cu1 N3i, 3.359 Å, symmetry code: (i) 2 x, y, 1 z). It is interesting to note that the dimer exist p p interaction between bdhc ligands while the p pi distance is 3.421 Å (symmetry code: (i) 2 x, y, 1 z, Fig. S1). The dimer further constructs a 1D supramolecular chain through N-H O hydrogen bonds (N2-H2 O8vii, 2.877(1) Å, symmetry code: (vii) 2 x, 1 y, 1 z, Fig. 2). The 1D supramolecular chain was formed 3D network through Br Br interaction (Br2 Br2ii,
3.538 Å; Br2 Br2iii, 3.880 Å; Br3 Br4iv, 3.880 Å; symmetry code: (ii) 3 x, 1 y, 1 z; (iii) 1 + x, y, z; (iv) 1 x, 0.5 + y, 0.5 z.) [52] and weak C-H Br hydrogen bonds (C20-H20A Br2v, 3.720 Å; C22-H22C Br4vi, 3.843 Å, symmetry code: (v) 1 + x, y, z; (vi) x, 1 + y, z.) and C-H O hydrogen bond (C6-H6 O6vii, 3.431 Å, symmetry code: (vii) 2 x, 1 y, 1 z.) (Fig. S2). 3.1.2. [Cu2(bbhc)(H2O)(dmf)2]NO3H2O (5) The structure of 5 is different from 1 to 4, because the NO 3 ion is free in 5 but in other four complexes are coordinated with Cu1 ion (Fig. 3). The dinuclear copper complex is formed by two Cu(II) ions,
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Fig. 1. Crystal structures of 1–4.
3.819 Å; symmetry code: (iv) 2 x, 0.5 + y, 0.5 z) [52], N-H O hydrogen bond (N2-H2 O6ii, 2.759Å) and O-H O hydrogen bonds (O10-H10B O10v, symmetry code: (v) x 1, y, z), and C-H O hydrogen bonds (C17-H17 O7iv, 3.095 Å; C19-H19 O8ii, 3.245 Å. Fig. S4).
3.2. Hirshfeld surface analysis Scheme 1. Coordination mode of the schiff base ligands.
one bbhc ligand, two DMF terminal ligands, one coordination water molecule, one counter anion nitrate and one lattice water molecule. The Cu1 ion is coordinated in a slightly distorted square–planar geometry by two nitrogen atoms and one oxygen atom from a bbhc ligand (Cu1–O1, 1.881(3) Å, Cu1–N1, 1.937 (4) Å, Cu1–N3, 1.979(3) Å) and one oxygen atom form DMF molecule (Cu1–O5, 1.960(3) Å). The coordination geometry of the Cu2 ion in 5 is similar to Cu2 of complexes 1–4. It must be note that the intramolecular, the Cu1 Cu2 distance of 5 is 4.792(1) Å which is the same as Cu1 Cu2 distance of 1–4. It is interesting to note that the 1-D chain was constructed by weak Cu O interaction (Cu1 O3i, 3.081 Å, symmetry code: (i) 1 + x, y, z, Fig. S3). The 1-D chain further formed double chain through strong O-H O hydrogen bonds (O6-H6AC O3ii, 2.772(4) Å, O6-H6AC O6iii, 2.772(4) Å, symmetry code: (ii) x, 1 y, 1 z, (ii) 1 x, 1 y, 1 z). It must be note that the double chains were formed 3-D supramolecular network through BrBr interaction (Br1Br2iv,
Hirshfeld surface is a useful tool for describing the surface characteristics of the molecules. The molecular Hirshfeld surface of the present five compounds were shown in Fig. 4. The dnorm surface is used to identify the very close intermolecular interactions. The dnorm values are mapped onto the Hirshfeld surface with a three-color scheme: where red regions correspond to that the closer intermolecular contacts than rvdW (van der Waals (vdW) radii); the blue regions correspond to longer intermolecular contacts than rvdW; and the white regions correspond to the distance of intermolecular contacts is exactly the rvdW. The deep red regions on dnorm surface indicate the close-contact interactions, which are mainly responsible for the significant hydrogen bonding contacts. For the present five complexes, these deep red regions are indicative of short contacts of N H, and O H interactions, which correspond to the N-H O and O-H O hydrogen bonds. (Fig. 4, Table 3). The small red regions on the dnorm surfaces are corresponding to the significant of C-H Br interactions. 2D fingerprint plots are an important supplement for the Hirshfeld surface. It is quantitatively describe the nature and type of intermolecular interactions between the molecules inside the crystals. The 2D fingerprint plots can be decomposed to highlight the
Fig. 2. 1D chain of 1.
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3.3. UV–vis spectrum The UV–vis spectra of complexes 1–5 are studied in the ranges 200–800 nm in DMF solution (3 105 M) (Fig. 6). Generally, for some Schiff bases derivatives from salicylaldehyde, there are no absorption bands were observed above 400 nm in polar and nonpolar solvents [53]. It must be note that a significant broad band was observed at 407, 414, 424, 415 and 415 nm for 1–5, respectively. The results indicated that the five molecules exist ligandto-metal-charge-transfer (LMCT) [54,55]. In addition, the UV–vis spectra of 1–5 showed another peak at 273 nm, 270 nm, 268 nm, 269 nm and 270 nm, respectively and it can be assigned to p ? p⁄ overlaps with charge transfer. According to the UV–vis spectra of 1–5, the complexes 1–5 showed two same peaks at 415 nm, and 270 nm. The results were consistent with structural analysis results. Fig. 3. Crystal structure of 5.
particular close contacts between atoms pair. The main intermolecular interactions of the five compounds is H H contacts which reflected in the middle of the scattered point of the 2D fingerprint plots (the percentage of H H contacts of 1–5 is 22.7%, 25.5%, 26.4%, 23.3% and 29.5%, respectively). The X H (X = Cl, Br) interaction is one of the most significant contacts for these compounds. For complex 1, the X H interactions are represented by a spike in the bottom left (donor) area of the fingerprint plot (Fig. 5), the H X interactions are represented by a spike in the bottom right (acceptor) region of the fingerprint plot. So we can infer that there are significant C-H X (X = Cl, Br) interactions are observed in both the compounds (the percentage of X H contacts of 1–5 is 20.4%, 24.0%, 23.9%, 22.0% and 13.0%, respectively). The other one significant interaction for these compounds is O H contacts. It is reflected in the 2D fingerprint plot and seems like the gums, which correspond to the large red regions of the dnorm surface. The percentage of O H contacts of 1–5 is 21.0%, 19.2%, 19.2%, 23.0% and 25.5%, respectively. Apart from those above, the presence of C H, C O, X X (X = Cl, Br) and other contacts are observed, and they are all summarized in Table 3.
3.4. Fluorescence properties In this study, fluorescence properties of the 1–5 and three ligands have been investigated at room temperature. Solid state luminescent properties of the free H3bchc, H3bbhc, H3bdhc ligands and five complexes 1–5 have been investigated at room temperature (Fig. 7). Upon photoexcitation at 380 nm, H3bchc, H3bbhc, H3bdhc ligands exhibit a green luminescent emission band with the maximum at 561, 566,563 nm, respectively while upon photoexcitation at 416 nm, complexes 1–5 exhibit a green luminescent emission band with the maximum at 632, 632, 632, 632, 630 nm, respectively. It must be note that the luminescent emission are assigned to p-p⁄ transition fluorescent. Compared to the free H3bchc, H3bbhc, H3bdhc ligands, the 1–5 exist about 70 nm red-shifted which due to the ligand to metal charge transfer (LMCT) excited state [56,57]. Emission intensities slowly decrease from H3bchc, H3bbhc, to H3bdhc ligands. In this study, luminescent properties of 1–5 have been investigated in DMF solvent with concentration of 1 104, 5 105, 1 105, 5 106, 1 106 mol/L, respectively (Fig. 8, Figs. S5–S8). Upon photoexcitation at 416 nm, complexes 1–5 exhibit a blue luminescent with the maximum at around 495 nm predominantly assigned to p ? p* transition fluorescent emission.
Fig. 4. Hirshfeld surface mapped with dnorm for complex 1–5.
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Table 3 The percentages of contacts between different element pairs contributed to the total Hirshfeld Surface area of molecules (X = Cl, Br). Complexes
H–H
C–H
O–H
X–H
C–C
C–O
Br–Br
Other
1 2 3 4 5
22.7 25.5 26.4 23.3 29.5
8.1 8.2 8.7 7.7 10.4
21.0 19.2 19.2 23.0 25.5
20.4 24.0 23.9 22.0 13.0
3.0 3.2 3.2 3.4 1.6
3.3 2.5 2.6 3.1 2.9
3.8 3.7 2.9 2.5 1.3
17.7 13.7 13.1 15.0 15.8
Fig. 5. Fingerprint plots of 1–5: Full (1) and resolved into X H (2), C H (3), H H (4) and O H (5) contacts showing the percentages of contacts contributed to the total Hirshfeld Surface area of molecules.
Compared to the emission intensity of the fluorescent in five different concentration solution, the fluorescence intensity of the complexes 1–5 were enhanced when the concentration of the of the solution were reduced [58,59]. The result indicates that fluores-
cence concentration self-quenching effect was observed in the solution of 1–5. Compared to the solid state luminescent of the complexes 1–5, with 135 nm blue-shifted, the blue-shifted is assigned to the aggregation induced emission [60].
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3.5. In vitro antitumor
Fig. 6. UV–vis spectra of complexes 1–5 together in DMF medium [concentration: 3 105 (M)].
Using the MTT method, the anti-proliferative activity of complexes 1–5 was evaluated against a panel of human tumor cells including BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SK-OV-3 and normal human liver HL-7702 cells. Each compound was prepared as 2.0 mM DMSO stock solution before they were diluted by PBS buffer to 20 lM aqueous solutions (containing 2% DMSO). As shown in Table 4, complexes 1–5 exhibited the cytotoxicity against BEL-7404, Hep-G2, NCI-H460, T-24, MGC-803, A549, SKOV-3. In contrast, complex 3 showed higher inhibitory rates against Hep-G2, NCI-H460, T-24, MGC-803, A549 and SK-OV-3 cells than other complexes. The inhibitory rates of complex 1 and 5 against BEL-740 and HepG2 are all higher than 30%. For T-24, MGC-803, A549, the inhibitory rates of complex 1, 2, 3, 5 are higher than 30%. All the complexes exhibited lower cytotoxicity against HL-7702 than that of cisplatin. The in vitro antitumor activity of complexes 1–5 was further quantified by determining the corresponding IC50 levels. As shown in Fig. 9 and Table 5, complexes 1–5 exhibited high IC50 values against BEL-7404, HepG2, NCI-H460, MGC-803 cells. Compared with the case of normal liver cell HL-7702, the cytotoxicity of complexes 2 and 4 toward the BEL-7404 tumor cells is enhanced by 4.5 and 3.1 times, respectively, which indicating the selectivity of complexes 2 and 4 on BEL-7404. Furthermore, in the cases of T-24, A549, SK-OV-3 cells, complex 3 displayed stronger cytotoxicity than cisplatin, with the IC50 values of 9.41 lM, 12.96 lM, 24.09 lM, respectively. Among them, T-24 cells showed the highest sensitivity to complex 3 with IC50 value of 9.41 ± 0.49 lM, which increased approximately 3-fold comparing with the cisplatin. Complex 3 may be a good candidate for anti-cancer drugs due to its high selectivity against T-24, A549 and SK-OV-3 cells. Compare to complexes 1–5, the bchc ligand in 3 and 4 has great capacity of electron-withdrawing substituent. On the other hand, at the apical position, ethanol molecules in 2 and 3 are easier to leave the complexes than methanol and water molecules in 1, 4, 5. As result, complexes 2 and 3 easier to become planar molecules than complexes 1, 4, 5. These two factors maybe result that complex 3 has good antitumor activity. 3.6. Magnetic property of 1
Fig. 7. Emission spectra of the 1–5 and the H3bchc, H3bbhc, H3bdhc ligands in a solidstate at room temperature.
Fig. 8. Solvent luminescence spectrum of the complex 1.
The magnetic susceptibilities of 1 were measured from crushed single crystalline samples under an applied field of 1 kOe for 1 at temperature range of 2–300 K (Fig. 10). The spin–orbit coupling of the two Cu(II) ions gives rise to a vMT product of 0.53 cm3 Kmol1 at room temperature. The vMT value at room temperature is slightly less than the spin-only value expected for two isolated Cu(II) ions that is 0.75 cm3Kmol1 with SCu = 1/2 and gCu = 2.0 [61]. It must be noted that the observed value of 1 is also slightly less than what was obtained for [Cu2(bpad)2(Hp)2]n (Hbpad = N3-benzoylpyridine-2-carboxamidrazone, H2p = phthalic acid) (0.875 cm3Kmol1) [61], [Cu2(l-Cl)2Cl2(pbba)2] (pbba = N-((pyridin-2-yl)benzylidene)benzylamine) (0.875 cm3Kmol1) [62]. With decrease in T, vMT value reduces to a minimum of 0.013 cm3Kmol1 at 50 K. Under 50 K, vMT of 1 remains constant till 2 K. To fit and interpret magnetic susceptibility data of 1, it is necessary to find all possible magnetic pathways. The intramolecular antiferromagnetic interaction in 1 is as expected keeping in mind that the exchange pathway involved is provided by one dinitrogen bridge between two Cu(II) ions of the dinuclear unit. Consequently, the dimeric nature of the 1 can be easily simplified to a Cu(II) dimer skeleton as schematized. Keeping the above considerations in mind, to calculate the magnetic exchange interaction (J)
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Table 4 The inhibitory effect on different cells of complexes 1–5(%). Complex
BEL-740
HepG2
NCI-H460
T-24
MGC-803
A549
SK-OV-3
HL-7702
1 2 3 4 5 Cisplatin
33.45 ± 1.54 45.71 ± 1.42 19.85 ± 0.16 35.47 ± 0.15 22.90 ± 3.62 55.15 ± 1.18
37.66 ± 1.41 20.38 ± 2.58 53.82 ± 1.93 38.96 ± 2.39 22.78 ± 1.42 60.63 ± 0.99
24.75 ± 1.79 34.88 ± 1.96 44.15 ± 2.73 35.79 ± 1.43 30.08 ± 2.46 50.88 ± 3.69
30.71 ± 1.38 30.72 ± 2.39 56.45 ± 1.20 28.45 ± 1.50 30.83 ± 3.39 37.38 ± 3.39
25.67 ± 1.76 41.87 ± 2.94 59.35 ± 2.12 47.38 ± 1.54 50.38 ± 3.87 71.35 ± 1.46
39.29 ± 1.52 35.17 ± 2.16 53.39 ± 4.37 13.94 ± 1.25 34.96 ± 3.19 51.14 ± 3.43
28.24 ± 1.78 36.06 ± 0.66 41.91 ± 2.02 26.94 ± 2.63 34.65 ± 1.01 46.56 ± 0.92
45.59 ± 1.74 15.38 ± 1.34 32.93 ± 1.59 17.97 ± 3.91 11.53 ± 0.81 73.58 ± 2.30
Fig. 9. IC50 (lM) values of complex 1–5 and cisplatin towards eight selected cell lines for 48 h.
Table 5 The IC50a on different cells of complexes 1–5 (lM).
a
Complexes
BEL-7404
HepG2
NCI-H460
T-24
MGC-803
A549
SK-OV-3
HL-7702
1 2 3 4 5 Cisplatin
31.68 ± 2.37 26.67 ± 0.39 46.04 ± 0.65 32.85 ± 2.79 112.47 ± 1.53 12.41 ± 0.38
36.41 ± 1.81 103.96 ± 2.25 13.04 ± 0.75 35.48 ± 0.88 56.04 ± 1.48 9.48 ± 0.35
39.42 ± 1.02 27.31 ± 0.51 22.86 ± 0.14 35.67 ± 1.52 32.22 ± 1.78 18.89 ± 1.02
34.22 ± 1.18 28.44 ± 0.60 9.41 ± 0.49 39.19 ± 1.16 35.41 ± 0.49 28.07 ± 1.88
78.07 ± 1.38 26.78 ± 1.02 8.29 ± 0.60 18.43 ± 1.53 13.76 ± 1.01 5.43 ± 0.45
78.07 ± 1.38 65.09 ± 1.65 12.96 ± 1.30 92.96 ± 1.29 27.35 ± 1.32 17.35 ± 1.34
57.35 ± 1.33 38.89 ± 1.49 24.09 ± 1.01 44.53 ± 1.58 34.53 ± 2.59 26.77 ± 0.89
36.77 ± 0.91 119.44 ± 1.42 37.99 ± 3.02 103.71 ± 1.50 128.30 ± 2.31 5.63 ± 0.32
IC50 values are presented as the mean ± SD (standard error of the mean) from five independent experiments.
between the copper centers in 1, the magnetic data was fitted to be modified Bleaney-Bowers equation expression for two interacting Cu(II) ions (S = 1/2) with isotropic spin Hamiltonian in the form ^ ¼ J ^ H S1 ^ S2 and it is given by Eq. (1). The best curve fitting gave 1
g = 1.99, J1 = -85.1 cm1, and R = 2.86 104. The R represents agreement factor and it is defined in Eq. (2). The negative J value represent obvious antiferromagnetic coupling between two Cu(II) centers in 1.
vM ¼ R¼
2Ng 2 b2 1 3 þ e2J=kT kT
X ðvm TÞexp ðvm TÞcal 2 ðvm TÞcal
ð1Þ ð2Þ
4. Conclusion Fig. 10. Plot of vMT and vM vs T measured in a 1000 Oe field for 1. The solid lines represent the best fits of data as described in the text.
Five new dinuclear copper complexes have been synthesized by modulating substituent of the schiff base ligands. The results of
H.-Y. Zhang et al. / Inorganica Chimica Acta 453 (2016) 507–515
vitro antitumor activity reveal that 3 exhibited a high apoptosisinduced ability against T-24, A549, SK-OV-3. Hirshfeld surface and fingerprint plot analysis of 1–5 revealed that the close contacts of these five complexes were dominated by H H, X H (X = Cl, Br), O H and C H interactions. There are significant N-H O, O-H O and C-H X (X = Cl, Br) interactions are observed in all the five compounds. The fluorescence indicates that fluorescence concentration self-quenching effect was observed in the solution of 1–5. On the other hand, magnetic studies reveal that there is antiferromagnetic interactions between two Cu(II) ions. Acknowledgments This work was supported by the National Nature Science Foundation of China (No. 21161006), the Nature Science Foundation of Guangxi Province of China (No. 2015GXNSFAA139031); Program for the scientific research and technology development plan of Guilin (No.20150133-5) and Program of the first session backbone teacher of Guangxi of China. Appendix A. Supplementary data Crystallographic data (excluding structure factors) for 1–5 in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC 1472827–1472831. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: 44 1223 336033, e-mail: [email protected]). Electronic supplementary information (ESI) available: [Dinmmer of 1 (Fig. S1), Packing diagram of 1. (Fig. S2), 1-D chain of 5 (Fig. S3), Packing diagram of 5 (Fig. S4). Solution state emission spectra of complexes 2–5 at room temperature (Figs. S5–S8)]. Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.ica.2016.09.013. References [1] S.H. Zhang, R.X. Zhao, G. Li, H.Y. Zhang, C.L. Zhang, G. Muller, RSC Adv. 4 (2014) 54837–54846. [2] A.W. Addison, T.N. Rao, J. Reedijk, J. van Rijn, G.C. Verschoor, J. Chem. Soc., Dalton Trans. (1984) 1349–1356. [3] S.T. Meally, C. McDonald, G. Karotsis, G.S. Papaefstathiou, E.K. Brechin, P.W. Dunne, L.F. Jones, Dalton Trans. 39 (2010) 4809–4816. [4] S. Demir, A. Güder, T.K. Yazıcılar, S. Çag˘lar, O. Büyükgüngör, Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 150 (2015) 821–828. [5] Y. Jia, J. Li, Chem. Rev. 115 (2014) 1597–1621. [6] P. Przybylski, A. Huczynski, K. Pyta, B. Brzezinski, F. Bartl, Curr. Org. Chem. 13 (2009) 124–148. [7] C. Yu, L. Jiao, P. Zhang, Z. Feng, C. Cheng, Y. Wei, E. Hao, Org. Lett. 16 (2014) 3048–3051. [8] M.D. Peterson, R.J. Holbrook, T.J. Meade, E.A. Weiss, J. Am. Chem. Soc. 135 (2013) 13162–13167. [9] L. Li, X. Hua, Y. Huang, X. Yang, C. Wang, J. Du, Synth. React. Inorg., Met.-Org., Nano-Met. Chem. 44 (2014) 291–294. [10] R.A. Kumar, M. Arivanandhan, Y. Hayakawa, Prog. Cryst. Growth Charact. Mater. 59 (2013) 113–132. [11] J.B. Pelayo-Vázquez, F.J. González, M.A. Leyva, M. Campos, L.A. Torres, M.J. Rosales-Hoz, J. Organomet. Chem. 716 (2012) 289–293. [12] T. Balic´, B. Markovic´, M. Medvidovic´-Kosanovic´, J. Mol. Struct. 1084 (2015) 82– 88. [13] Y. Xiao, Y. Qin, M. Yi, Y. Zhu, J. Clust, Science (2016), http://dx.doi.org/10.1007/ s10876-016-1059-y. [14] P.A. Vigato, V. Peruzzo, S. Tamburini, Coord. Chem. Rev. 256 (2012) 953–1114. [15] R. Sessoli, D. Gatteschi, Angew. Chem. Int. Ed. 42 (2003) 268–297.
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