Microwave Solvothermal Synthesis, Crystal Structures and inVitro Antitumor Activities of Di-n-butyltinPiperonylatewith aSn4O4 Ladder Framework①

KUANG Dai-Zhi FENG Yong-Lan JIANG Wu-Jiu ZHU Xiao-Ming YU Jiang-Xi ZHANG Fu-Xing

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Microwave Solvothermal Synthesis, Crystal Structures andAntitumor Activities of Di--butyltinPiperonylatewith aSn4O4Ladder Framework①

KUANG Dai-Zhi②FENG Yong-Lan JIANG Wu-Jiu ZHU Xiao-Ming YU Jiang-Xi ZHANG Fu-Xing

(Key Laboratory of Functional Metal-organic Compounds of Hunan Province, Key Laboratory of Functional Organometallic Materials of Hengyang Normal University, College of Hunan Province, College of Chemistry and Material Science, Hengyang Normal University, Hengyang 421008, China)

A two-dimensional supramolecular compound di--butyltin piperonylate, {(3- O)(2-OMe)(-Bu2Sn)2[O2CAr(C2H4O)]}2constructed by hydrogen bonds with a Sn4O4ladder-like framework, was obtained by the microwave-assisted solvothermal reaction of di--butyltin oxide precursor with the piperonylic acid in methanol environments. The composite was characterized by elemental analysis and IR (1H,13C and119Sn) NMR spectra. The compound crystallizes in monoclinic system, space group21/with= 13.3690(12),= 14.1442(14),= 16.4022(16) ?,= 107.191(6)°,= 2963.0(5) ?3,= 2,D= 1.520 g/cm3,(000) = 1368,= 1.719 mm-1, Moradiation (= 0.71073 ?), the final= 0.0495 and= 0.1260 for 6780 observed reflections with> 2(). Its X-ray crystallography diffraction analyses show a Sn4O4ladder-like skeleton, in which two endocyclic tin and one exo tin atoms are bonded to the3-O atom. In addition, one endocyclic tin and one exo tin atoms are respectively bonded to the2-O atom from methanol. The ladder-like molecule has a three-ring fused skeleton, which is almost coplanar. The endocyclic and exocyclic tin atoms were all five-coordinated with distorted trigonal bipyramidal geometry. The antitumor activity showed that the compound had higher activities than cisplatin in HT-29, HepG2, MCF-7, KB and A549 cell line.

di--butyltin piperonylate, microwave solvothermal synthesis, ladder-like framework,antitumor activity;

1 INTRODUCTION

In recent years, organotin carboxylates are an important family of organotin compounds and are receiving attention for a variety of reasons including their biological[1-5], catalytic activity structural diversity as well as their wide industrial and agricul- tural applications[6-9]. Among various organotin carboxylates, the organotin carboxylates have been, due to many interesting structural types, the subject of extensive investigation.Studies show that the structure of organotin carboxylate is related to the number of alkyls attached to tin atoms[10-13], the type of carboxylate ligands[14-16], the reaction condi-tions, etc. For example, the reaction of-Bu2SnO with-aminobenzoic acid in a 1:2 ratio resulted in the formation of a monomer[17], while that of 1:1 ratio led to a centrosymmetric dimer[18].In order to further investigate the relationship between the structure of organotin carboxylate with ligand carboxylic acid and the reaction conditions, in this paper, a two-dimensional supramolecular compound, di--butyltin piperonylate, has been obtained by microwave assisted solvothermal synthesis technology.

2 EXPERIMENTAL

2. 1 Materials and instruments

-Bu2SnO is commercially available and used without further purification. Piperonylic acid was procured from Sun Chemical Technology Co., Ltd (Shanghai, China). Elemental analyses for C, H and N were determined on a PE-2400(II) analyzer. IR spectrum was obtained for KBr pellets on a Shimadzu IR Prestige-21 spectrophotometer in the 400～4000 cm-1region.1H and13C NMR spectra were recorded with a Bruker INOVA-400 NMR spectrometer operating at 400 and 100 MHz, respectively.119Sn NMR spectra were recorded with a Bruker INOVA-500 NMR spectrometer operating at 186 MHz. Chemical shifts were given in ppm relative to Me4Si and Me4Sn in CDCl3solvent. Crystal structure was determined on a Bruker Smart Apex II CCD diffractometer. Melting point was measured on an XT-4 binocular micromelting point apparatus with the temperature uncorrected. MicroSYNTH Microwave Labstation was applied for Synthesis (Italy).

2. 2 Synthesis

A mixture of di--butyltin oxide (1 mmol, 0.249 g), piperonylic acid (1 mmol, 0.166 g) and methanol (30 mL) was placed in a 50 mL Teflon-lined reactor, Set on the microwave power 800W of MicroSYNTH Microwave Lab station for synthesis. This mixture was heatedto 120 ℃in 30 minutes.After microwave radiation of 2 h, the reactants were naturally cooled to room temperature. The solution was obtained by filtration, and the filtrate was removed by evaporation in vacuo. Crystals of compound were obtained on recrystallization from methanol.The product was yellow-brown crystals in 56.3% yield (based on-Bu2SnO). m.p.: 121～123 °C. Anal. Calcd. (%) for C50H88O12Sn4: C, 44.29; H, 6.54. Found (%): C, 44.38; H, 6.82. IR:(C-H)2956, 2925(s), 2855(m),(COO-) 1631(s),(COO-)1372(m),(Sn-O-Sn)621(w),(Sn-C)553 (w),(Sn-O) 421(w) cm-1.1H NMR (CDCl3)(ppm): 0.90 (t, 24H,= 7.2, -CH3, hydrogen protons of-butyl groups). 1.37～1.68 (m, 48H, SnCH2CH2CH2, hydrogen protons of-butyl groups); 3.49 (s, 6H, -OCH3); 6.00 (s, 4H, -OCH2O2-); 6.79 (s, 2H, Ar-H); 7.42 (s, 2H, Ar-H); 7.57 (s, 2H, Ar-H).13C NMR (CDCl3)(ppm): 13.58～27.61 (-Bu-C); 50.76, 51.12 (-OCH3); 101.38 (-OCH2O2-); 107.43, 107.46, 109.88, 124.69, 127.83, 147.35 (Ar-C); 171.32 (-COO).119Sn NMR (CDCl3)(ppm): –173.74, –211.12. The crude adduct was recrystallized from suitable solvent to give purified crystals.

2. 3 X-ray crystal structure determination

A yellow-brown single crystal of the compound with dimensions of 0.18mm × 0.17mm × 0.15mm was selected. The data were collected by a Bruker Smart Apex II CCD diffractometer (Moradiation,= 0.71073 ?) in the ranges of 2.15≤≤27.54o, –16≤≤17, –16≤≤18 and –21≤≤21. A total of 19651 reflections were collected and 6780 were independent (int= 0.0301), of which 3564 observed reflections with> 2() were used in the succeeding refinements. The full-matrix least-squares refinement on2(SHELXL-97) was performed with all non- hydrogen atoms anisotropically determined. Hydro- gen atoms were placed in the calculated positions or located from difference Fourier maps, and refined isotropically with the isotropic vibration parameters related to the non-hydrogen atom to which they are bonded. All calculations were performed with SHELXL-97[19]programs within WINGX[20]. A full-matrix least-squares refinement gave the final= 0.0532 and= 0.1496 (= 1/[2(F2) + (0.1018)2+ 1.0075], where= (F2+ 2F2)/3),= 1.005, (Δ)max= 0.657 and (Δ)min= –0.588 e/?3.

2. 4 Antitumor studies

Human colon cancer (HT-29), human hepato- celluar carcinoma (HepG2), michigan cancer foun- dation (MCF-7), oral human epidermoid carcinoma (KB) and human lung cancer cells (A549) were obtained from American Tissue Culture Collection (ATCC). The cells were maintained at 37 °C in a 5% CO2incubator in RPMI 1640 (GIBICO, Invitrogen) containing 10% fetal bovine serum (GIBICO, Invitrogen) for cell proliferation and growth inhibition assay. Cell proliferation was assessed by MTT assay. The cells were exposed to treatment for 72 h, and the number of cells used per experiment for each cell line was adjusted to obtain an absorbance of 1.3 to 2.2 at 570 nm. Six concentrations (0.1 nM ～ 10 μM) were set for the compounds and at least 3 parallels of every concentration were used. All experiments were repeated at least three times. The data were calculated using Graph Pad Prism version 5.0. The IC50was fitted using a non-linear regression model with a sigmoidal dose response.

3 RESULTS AND DISCUSSION

3. 1 Spectral characteristics

The IR and (1H,13C and119Sn) NMR spectra of the compound have obvious characteristics. The stre- tching frequencies of interest are those associated with the COO, Sn–C, Sn–O and Sn–O–Sn groups. The two different absorption bands in 1631 and 1372 cm-1correspond to theν(COO) andν(COO) modes of the coordinated carbonyl groups. The difference Δ(ν(COO) –ν(COO)) between these frequencies is 259 cm-1and found for monodentate[21-25]. A band in 553 cm-1is assigned to the stretching frequency associated with the(Sn–C) bond[26, 27], while two bands at 421 and 621 cm–1are attributed to(Sn–O) and(Sn–O–Sn) stretching modes[28], respectively.

The1H NMR spectra show the expected integra- tion and peak multiplicities. The-butyl protons in the compound show a multiple resonance due to -CH2-CH2-CH2- skeleton in the range of 1.37～1.68 ppm and clear triple due to the terminal methyl groups at 0.90 ppm[29, 30], respectively. It is shown that the chemical shifts of the protons on the phenyl groups exhibit signals at 6.79～7.57 ppm as signals or multiplets, the three hydrogen protons on coor- dinated methanol of compound at 3.49 as single peak[31], and the methylenedioxy protons (O–CH2–O) of 3 at 6.00 ppm as single peak[32].

The13C NMR spectra of the compound show a significant downfield shift of carboxylate carbon resonances compared with the free ligands. The shift is a consequence of electron density transfer from the ligand to the Sn atom. The single resonances at 171.32 ppm are attributed to the carbon of carboxyl groups.

The119Sn NMR chemical shifts of organotin(IV) carboxylates appear to depend not only on the alkyl groups bound to the metal ion, but also on the types of ligand and coordination number[33]. The signal at –171.32 ppm is the character of Sn NMR.

3. 2 Structural description

The molecular structure of the compound is shown in Fig. 1, and the selected bond distances and bond angles are listed in Table 1. The crystal structure shows a ladder framework and features2-coordination of -OCH3. Each methanol molecule adopts anisobidentate chelating coordination modes (Sn(1)–O(4) 2.248(6) ? and Sn(2)–O(4) 2.130(5) ?), while the carboxylic groups of aromatic monocarboxylic acid ligand coordinate with the Sn atom as a unidentate bonding (Sn(1)–O(1) 2.118(11)?). These values fall in the typical Sn–O bond length range. These structures of the ladder parts were very similar to the compound [(-Bu2Sn)2(-Bu2SnFcCOO)2(-O)2(-OCH3)2]2[12]. In the Sn4O4ladders, the four tin atoms are almost coplanar (Fig. 2) with the torsion angles largest deviation being 0.21°. According to their different coordination environments, the four tin atoms can be divided into two types: the endocyclic tin (Sn(2) and Sn(2i)) and the exocyclic tin (Sn(1) and Sn(1i)). The endocyclic and exocyclic tin atoms are connected by the3-oxygen atoms (O(3) and O(3i)) and the2-oxygen atoms (methanolic oxygen O(4) and O(4i)). Tin atoms of the compound are five-coordinated by two-butyl groups and three O atoms, resulting in-Bu2SnO3coordination environments with the two-butyl groups and one O atom in equatorial positions and the other two O atoms in axial positions, thus forming a distorted trigonal bipyramid.

Table 1. Selected Bond Lengths (?) and Bond Angles (°)

Symmetry code for compound: i: –+1, –+1, –+1

Fig. 1. Molecular structure of compound (Ellipsoidal probability level 10%)

Fig. 2. Oxygen and tin atom coplanar coordination environment (butyl groups are omitted for clarity)

It is worth noting that the crystal packing of the molecular structure, a two-dimensional supramole- cular structure, was formed by the hydrogen bonding C(16)–H(16B)···O(6i) interactions of the neighboring molecules, Fig. 3.

i0.5–, 0.5+, 1.5–;ii0.5+, 1.5–, –0.5+

Fig. 3. Two-dimensional supramolecular constructedthe hydrogen bonds (butyl groups are omitted for clarity)

3. 3 Antitumor activity

The antitumor activities in vitro by MTT assay against HT-29, HepG2, MCF-7, KB and A549 cell lines of compound were evaluated. The screening result indicates strong cytotoxic effects against the tested carcinoma cell lines with a lower IC50value, as listed in Table 2. The strong anticancer activity of aromatic di--butyltin carboxylates has been further confirmed and supported by this experiment[38-40].

Table 2. IC50 (μM) of Compound and Cisplatin on Tumor Cells in Vitro

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13 December 2017;

2 May 2018 (CCDC 892011)

the Innovation Platform Open Foundation for Colleges and Universities of Hunan Province (No. 16k011), Key Laboratory of Functional Organometallic Materials of Hengyang Normal University (No. GN16K01) and Scientific & Technological Projects of Hengyang (No. 2016KJ03)

. Tel: 0734-8484932, E-mail: hnkcq@qq.com

10.14102/j.cnki.0254-5861.2011-1923