ZHANG Fu-Xing WU Qian KUANG Dai-Zhi YU Jiang-Xi JIANG Wu-Jiu ZHU Xiao-Ming

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Synthesis, Crystal Structure and Properties of A Triphenyltin Schiff Complex with Salicylidene-2-aminophenol①

ZHANG Fu-Xing②WU Qian KUANG Dai-Zhi YU Jiang-Xi JIANG Wu-Jiu ZHU Xiao-Ming

(421008)

The triphenyltin complex with salicylidene-2-aminophenol (C31H24NO2Sn, 1) has been synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and X-ray single-crystal diffraction.The complex crystallizes in monoclinic system,21/space group with= 1.09515(8),= 1.17739(8),= 2.29075(14) nm,= 117.070(4)°,= 2.6302(3) nm3,= 4,D= 1.417 g/cm3,= 0.999 mm–1,(000) = 1123,= 0.0472 and= 0.1169. X-ray single-crystal diffraction showed that 1demonstrates a one-dimensional chain structure.The quantum chemical calculation of 1 has been investigated.Complex 1 emits fluo- rescence at 558 nm and exhibitscertain inhibitory activity against NCI-H460, A549 and MCF-7.

triphenyltin complex with salicylidene-2-aminophenol,organotin, synthesis, crystal structure, vitro anticancer activity;

1 INTRODUCTION

Schiff bases, which have been widely used as a chelating agent, surfactant, analytical reagent and catalyst in the scientific and research in chemical production, are one of the most important organic compounds. Schiff base ligands can provide dif- ferent coordination modes in momo- or multidenta- te-fashion, and show various performances and diverse structures. Meanwhile, they are easy to form complexes with most of the metal ions. Furthermore, most studies have shown that the C=N linkage is essential for biological activity. Thus, Schiff bases have play an important role in the development of coordination chemistry with significance of both chemistry and biology. Hodnett grouphave reported some Schiff base derivatives with C=N bonds have certain anti-tumor activity, when they coordinate with metal ions to form complexes, whose antitumor effects have be more obvious[1, 2].

On the other hand, organotin complexes have multiple configurations,rich reaction styles, strong biological activities, and wide applications. In addition, the conclusion has also been obtained thattheir structures and performances depend on the hydrocarbyl structures which are directly linked to tin atom and the type of ligands[3 -7]. Functionalized ligands can greatly change the coordination modes of tin atoms, and significantly affect the bioactivity of organotin compounds to regulate the balance between their toxicity and biological activity. Researches show that the organotin can chelate the Schiff bases to obtain complexes with a variety of forms and rich structures, and it can significantly enhance their biological activities[8-11].Thetriphe- nyltin Schiff complexes with salicylidene-2-amino- phenol have been studied[12, 13]. In order to further explore the relationship between their structures and performances, a new organotin Schiff complex has been synthesized and characterized by EI, IR, TGA, and X-ray single-crystal diffraction. We analyze the structure usingcalculations and discuss the stability of the complex molecule, the molecular orbital energy and the composition characteristics of some frontier molecular orbitals. Moreover, the fluorescence properties and antitumor activity of 1 have been investigated.

2 EXPERIMENTAL

2. 1 Materials and chemicals

IR spectra were recorded with a Japan Shimadzu FTIR-8700 infrared spectrometer in 4000～400 cm–1region using KBr pellets. The elemental analysis was determined by PE-2400 (II) elemental analyzer. Crystallographic data of the complex were collected on a Bruker SMART APEX ⅡCCD diffractometer. Melting points were measured using an X4 digital microscopic melting point apparatus without correc- tion. Thermogravimetric analyses were executed on a TGA Q50 thermogravimetric analyzer. Fluores- cence spectroscopy was performed on an F-7000Fluorescence Spectrometer. The salicylidene-2-ami- nophenol Schiff base was synthesized according to the literature[12]and the other reagents were chemi- cally pure and used directly without further puri- fication.

2. 2 Synthesis of complex 1

Complex 1 was synthesized according to a literature method[13]. A reflux condenser pipe with CaCl2drying tube was installed in a dry two-necked flask (50 ml), which was fixed on an electroma- gnetic stirring heater. After a mixture of anhydrous ethanol (40 mL) and ether (2 mL) was added and stirred for 1 minute, Na (0.05 g) was cut into small pieces to add the flask, and plugged the side mouth of the flask. When Na was reacted completely, 0.426 g salicylidene-2-aminophenol Schiff base was added into the above mixture. After refluxing with heating for 10 minutes, 0.771 g triphenyltin chloride was added and refluxed with stirring for 5 h. The precipitate was filtrated while hot, the part of the solvent of the filtrate was removed by rotary evaporation. The rest of filtrate was placed at room temperature to obtain the brown solid triphenyltin complex with salicylidene-2-aminophenol. After recrystallization with suitable solvent, the trans- parent strawberry crystal of 1 (0.769 g) was collected with a yield of 68.54%. m.p.: 218～221℃.Anal. Calcd. (%): C, 66.36; H, 4.31; N, 2.50. Found (%): C, 66.64; H, 4.28; N, 2.47. IR (KBr, cm-1): 3062.96(m), 3053.73(m), 1604.77(s), 1589.34(s), 1537.26(s), 1465.90m), 1429.25(m), 534.28.0(w), 474.49(w).

2. 3 Crystal structure determination

A suitable sample of size 0.36 × 0.29 × 0.23 mm for 1 was chosen for the crystallographic study and then mounted at 296(2) K on a Bruker SMART APEX Ⅱ CCD diffractometer equipped with graphi- te-monochromated Moradiation (= 0.071073 nm) with ascan mode in the range of 2.00≤≤25.00°. A total of 13614 (4606 independent,int= 0.0351) reflections were measured, of which 4152were observed (＞ 2()). All the data were corrected byfactors and empirical absorbance. The structure was solved by direct methods. All non-hydrogen atoms were determined in successive difference Fourier synthesis, and all hydrogen atoms were added according to theoretical models. All hydrogen and non-hydrogen atoms were refined by their isotropic and anisotropic thermal parameters through full-matrix least-squares techniques. All calculations were completed by the SHELXTL-97 program[14]. The final= 0.0472,= 0.1169, (Δ)max= 929 and (Δ)min= –546 e/nm3. The selected bond lengths and bond angles for 1 are listed in Table 1.

Table 1. Selected Bond Distances (nm) and Bond Angles (°) of Complex 1

2. 4 Anti-tumor activity of 1

The proliferation inhibition activities of the complex against NCI-H460, A549 and MCF-7 were measured by means of MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) assay.The experiments are divided into drug group (with different concentrations of the complex), control group (without the complex) and blank group (without the complex and cells). The tumor cells in logarithmic phase were chosen and digested by the suitable amount of Trypsin to make the adherent cell fall off, and then the cells were cultured in RPMI- 1640 medium supplemented with 10% fetal bovine serum (FBS) and grown at 310 K in a humidified atmosphere in the presence of 5% CO2. Harvested cells were seeded into 96-well plate with various concentrations of the complex (0.1～10mol·L–1) and incubated for 72 h. Each concentration of the complex was set in parallel for six wells. Before four hours to the end of incubation, 40L of MTT solution (4 mg·mL–1in D-Hanks) was added to each well containing fresh and cultured medium. At the end, the insoluble formazan produced was com- pletely dissolved in DMSO (150L) by incubating for 5 min on a shaker and optical density (OD) was read against reagent blank with automatic immune enzymatic analytic system (Ap22 Speedy) at a wavelength of 570 nm. The cell proliferation inhi- bition activities of the positive control (carbonplatin) were determined by the above similar assay. Experi- mental data were analyzed with nonlinear regression of the survival percentage to the drug concentration (curve fitting) using Graph Pad Prism 5.0 and the IC50values were determined using sigmoidal dose response equation (variable).

3 RESULTS AND DISCUSSION

3. 1 Crystal structure of complex 1

X-ray single-crystal diffraction analysis reveals that 1 features an extended 1chain structure (Fig. 3)constructed of triphenyltin and salicylidene-2- ami- nophenol. As shown in Fig. 1,the central tin atomis in a distorted [SnC3O2] trigonal bipyramid, of whichthe coordination sphere for Sn1is defined by three phenyl carbon atoms and two oxygenatoms of phenolic hydroxyl from different ligands. Three carbon atoms of benzene ring (C(14), C(20), C(26)) occupied the equatorial plane of triangular bipy- ramid while two oxygen atoms (O(1), O(2)) locate at the axial positions on either side of the equatorial plane. The Sn–C and Sn–O distances are in the ranges of 0.2124(3)～0.2133(3) and 0.2216(2)～0.2228(2) nm, respectively, and the sum of angles around tin atom in the equatorial plane is 360.01o, which is very small with 360o, suggesting that three carbon atoms and the tin atom are coplanar well. Meanwhile, the angles O(1),–C–O(2) are about 86.74°～92.29°, where carbon atoms are at the equator. These angles have a minor deviation from 90°. In the axial direction, the angle of O(1)– Sn(1)–O(2) (177.31°) is close to be linear (180°). Thus the trigonal bipyramid [SnC3O2] is little distorted. It is worth noting that, in the structure determination process, N(1) and C(13) atoms were conducted with 50% C and 50% N model according to the method of literature[15, 16]because the crys- tallographic symmetry is higher than the complex one.

Fig. 1. Unit of the crystal structure of 1

Fig. 2. Packing of 1 in a unit cell

Fig. 3. 1chain structureof complex 1

3. 2 Analysis of the energy and frontier molecular orbital composition

3. 2. 1 Total and frontier molecular energy

According to the coordinate site of each atom in the crystal structure as well as symmetric geometry, a structural unit was applied to Gaussian 03W program to perform quantum chemistry single-point calculation at the B3ylp/lanl2dz level. After calcu- lation, the total energy of the complex system is –1401.2007434 a.u, those of the highest and lowest occupied molecular orbital (HOMO and LUMO) are –0.09621 and 0.04334 a.u., respectively, and the energy gap (Δ) between the HOMO and LUMO is 0.05287 a.u.. Although the total energy is lower, the energy of HOMO is higher and the energy gap (Δ) is small. These prove that complex 1 is stable under the certain conditions. However, it is easy to be stimulated. From the point of oxidation-reduction and charge transfer, complex 1 is easy to lose electrons to oxidize. Thus, the stability of complex 1 is limited.

3. 2. 2 Molecular orbital composition

In order to explore the electronic structure and bonding characteristics of complex 1, the molecular orbitals were investigated systematically.The contribution of one atom to the molecular orbital was denoted as the sum of square of orbital coef- ficient and normalization.Complex 1 was divided into six parts: (i) Sn atom; (ii) C atom of phenyl; (iii) C atom of ligand; (iv) O atom; (v) N atom, (vi) H atom. The highest and lowest occupied molecular orbital were studied, respectively. The calculation results are shown in Table 2 and Fig. 4.

The conclusions can be obtained:(i) the largest contribution for the energy is C atoms toreach67.26%; (ii) the second one is nitrogen atoms which occupy18.65%; (iii) the contributions of O and C atoms of phenyl are 9.51% and 3.50%, respectively, while the Sn atoms only contribute 0.26%, indicating that theSn–C and Sn–O have a limited stability. Compared to HOMO and LUMO orbital composition, it is found that when the electron of complex 1 transfers from HOMO to LUMO. It is primary that the electrons of ligands transfer to the central Sn atom and the phenyl ring as a whole.

Fig. 4. Schematic diagram of frontier MO for complex 1

Table 2. Calculation of Some Frontier Molecular Orbitals Composition of 1

3. 3 Thermal stability

Thermogravimetric analysis was carried out in air atmosphere from 40 to 700 ℃ at a heating rate of 20 ℃·min–1and gas flowing velocity of 20 mL·min–1. As shown in Fig. 5, complex 1 had no loss at40～210 °C, the weight loss in the tempera- ture range of 210～315 ℃ was rapider than that at 315～435 ℃, and the loss stopped until435 ℃. The total loss of 71.95% was attributed to the elimination of three phenyls and ligand. A final residue was SnO2(obsd. 28.05%, calcd. 26.86%).The above thermogravimetric results indicate that complex 1shows good thermal stability below 210 ℃.

Fig. 5. Thermogravimetric analysis curve of 1

Fig. 6. Fluorescence spectra of complex 1

Fig. 7. Absorption spectra of complex 1 and the ligand

3. 4 UV and luminescence properties

The UV and luminescent behaviors of 1 as well as free ligandalicylidene-2-aminophenol were inves- tigated in the methanol with the concentration (1 × 10–4mol/L) at room temperature, as shown in Figs. 6 and 7. When excited with 348 nm light, the ligand exhibits luminescent spectra with intense emission at 600 nm, while complex 1 displays a similar emission peak at 540 nm (ex= 437 nm). In contrast to the ligand, the absorption spectra of 1 show a blue shift with decreasing absorption intensity. The most possible reason is that when the ligand coordinated to tin atoms, the charge transfer happened between them and the electron cloud density of the conjugate system was reduced. The results also reveal that the organic tin had a certain effect of fluorescence quenching on the salicylidene-2-aminophenol Schiff bases.

3. 5 Fluorescence quantum yield and fluorescence lifetime

The luminescence quantum yields of ligand and 1 were measured in spectrographic solvent in the quartz cell with 1 cm. The slit widths of excitation and emission spectra were set to 5 nm. In order to minimize the heavy absorption, the absorbance of the sample is below 0.05. It was cited relative to a NaOH solution of fluorescein (stand= 0.92) as a standard, and they were calculated according to the well-known equation:samp= (stand×samp/stand) × (samp/stand) × (samp2/stand2).The quantum yields of the ligand and 1 were 0.31 and 0.21, and their lifetimes were 2.14 and 2.58 ms, respectively.

3. 6 Anti-tumor activityof complex 1

Theantitumor activity test results showed that complex 1 exhibited different IC50values of 0.82 ± 2.2, 2.4 ± 0.3 and 15.5 ± 1.9mol·L-1to A-549, NCI-H460 and MCF-7, whereas, the ligand had IC50values of 20.64 ± 1.6, 8.96 ± 2.13 and 30.5 ± 0.6, respectively.These results suggest that complex 1 has stronger inhibitory activity on human cancer cells than the ligand. Furthermore, the inhibitory abilities of the complex against A549 and NCI-H460 are better while it is weaker against MCF7. The detailed biological activities of complex 1 will be in-depth studied.

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19 April 2017;

20 October 2017

10.14102/j.cnki.0254-5861.2011-1684

①the Open Fund Project of Key Laboratory of Functional Organometallic Materials of Hengyang Normal University (15K017, 14K014, 13K105), Natural Science Foundation of Hunan Province (No. 13JJ3112), Scientific & Technological Projects of Hunan Province (No. 2014NK3086), Aid programs for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province, the Key Discipline of Hunan Province and Project funding for research and innovation experiment of university students in Hunan Province

②. E-mail: zfx8056@163.com